Monthly Archives: July 2021

Launching today: eLearning programme to support advanced therapy training in the NHS, UK universities and government bodies – PharmiWeb.com

Posted: July 21, 2021 at 2:20 am

Launching today: eLearning programme to support advanced therapy training in the NHS, UK universities and government bodies

UK, 19th July 2021 The Advanced Therapy Treatment Centre (ATTC) network, London Advanced Therapies (LAT) and the Cell and Gene Therapy Catapult (CGTC), in partnership with Health Education England elearning for healthcare, have developed a new eLearning programme targeted at healthcare and academic professionals to support their learning on both the fundamentals and clinical adoption of advanced therapies.

This series of eLearning sessions is designed to give the learner a core understanding of advanced therapies, how they function in the body, and the steps involved in delivering these medicines. The modules take the learner from the basics of cell and gene therapy, through to a more in-depth look at products currently being delivered through both commissioned treatments and clinical trials.

Advanced therapy medicinal products (ATMPs) are medicines for human use, which use genes, tissues or cells to offer ground-breaking new opportunities for the treatment of disease and injury. These therapies are potentially curative and can offer the promise of treating and altering the course of diseases which cannot be addressed adequately by existing pharmaceuticals, offering a lifeline to some patients who may have exhausted all other treatment options.

Learners will also be introduced to the unique challenges of bringing these pioneering advanced therapy treatments to patients, including the often nuanced logistical and handling requirements that can present unique challenges within usual standard of care.

The sessions, which can be mixed and matched according to the learners needs, comprise the following topics:

For more information and to access the sessions, visit the programme page https://www.e-lfh.org.uk/programmes/advanced-therapy-medicinal-products/

Professor Uta Griesenbach, Professor of Molecular Medicine, Imperial College London and Chair of the pan-UK ATMP Training Group commented:

As more ATMPs enter late-stage clinical trials, we identified a training need for healthcare professionals to ensure fast development of ATMPs and smooth transition into the NHS. This is a fantastic example of collaboration between NHS, academia and industry, coordinated by CGTC to produce valuable training for UK personnel and future-proof the healthcare system. Access to these sessions sets the UK apart from other countries by making high quality, standardised training available to all staff involved in the delivery of these life-changing medicines.

Professor Fiona Thistlethwaite, iMATCH Director, Medical Oncology Consultant and Christie NHIR CRF Director commented:

Providing comprehensive training for staff to understand the complex requirements of these new therapies is essential as we scale up our delivery of ATMPs across multiple patient groups. With input from recognised ATMP experts from the ATTC network and NHS partners across the UK, staff can now use the information provided to support their continued professional development. This tailored online learning approach also allows our staff to build their knowledge in a way that fits around their schedules.

About Health Education England elearning for healthcare

Health Education England elearning for healthcare (HEE elfh) works in partnership with the NHS, third sector and professional bodies to support patient care by developing eLearning resources to educate and train the health and care workforce. The eLearning programmes cover content from anaesthesia to dentistry, end of life care to mental health, and population wellbeing to sepsis. Users can access statutory and mandatory training, obtain certificates and complete eLearning sessions relevant to their role. For more information about elfh visit http://www.e-lfh.org.uk

About the Advanced Therapy Treatment Centre (ATTC) network

The Advanced Therapy Treatment Centre network was set up to address barriers to the clinical adoption of advanced therapies by increasing the capacity and capability of the NHS to efficiently deliver the growing number of these new medicines. The network is coordinated by the Cell and Gene Therapy Catapult and comprises partners in industry, academia and healthcare providers and three regional UK centres: Innovate Manchester Advanced Therapy Centre Hub (iMATCH); the Midlands-Wales Advanced Therapy Treatment Centre (MW-ATTC, comprising Birmingham, Bristol, Cambridge, Cardiff, Leicester, Nottingham and Swansea); the Northern Alliance Advanced Therapies Treatment Centre (NA-ATTC, comprising Edinburgh, Glasgow, Leeds and Newcastle). The network was established through funding from the Industrial Strategy Challenge Fund, and the fund is delivered by UK Research and Innovation. For more information please visit theattcnetwork.co.uk.

About London Advanced Therapies

London Advanced Therapies (LAT) brings together the London scientific community working in the field of Cell and gene based therapies. Funded by research England and led by Kings College London, Imperial College London and University College London, LAT aims to catalyse Londons capabilities and outputs in the area of advanced therapies, through fostering collaborative work, facilitating commercial partnerships and creating a microclimate for innovation. Established in 2019, LAT is rapidly expanding, working with colleagues throughout the UK to establish a nationwide Network of Networks.

About the Cell and Gene Therapy Catapult

The Cell and Gene Therapy Catapult was established as an independent centre of excellence to advance the growth of the UK cell and gene therapy industry, by bridging the gap between scientific research and full-scale commercialisation. With more than 350 employees focusing on cell and gene therapy technologies, it works with partners in academia and industry to ensure these life-changing therapies can be developed for use in health services throughout the world. It offers leading-edge capability, technology and innovation to enable companies to take products into clinical trials and provide clinical, process development, manufacturing, regulatory, health economics and market access expertise. Its aim is to make the UK the most compelling and logical choice for UK and international partners to develop and commercialise these advanced therapies. The Cell and Gene Therapy Catapult works with Innovate UK. For more information please visit ct.catapult.org.uk or visit http://www.gov.uk/innovate-uk.

About the Industrial Strategy Challenge Fund

This project has been funded by the Industrial Strategy Challenge Fund, part of the governments modern Industrial Strategy. The fund is delivered by UK Research and Innovation.

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Anthos Therapeutics’ novel Factor XI inhibitor abelacimab significantly outperforms standard of care enoxaparin in prospective Phase 2 efficacy…

Posted: July 21, 2021 at 2:20 am

DetailsCategory: AntibodiesPublished on Tuesday, 20 July 2021 18:19Hits: 299

Abelacimab achieved a ~80% reduction in venous thromboembolism versus a standard of care comparator in gold standard proof-of-concept efficacy study, indicating its potential in a range of thromboembolic disorders

CAMBRIDGE, MA, USA I July 19, 2021 I Anthos Therapeutics, a clinical-stage biopharma company developing innovative therapies for cardiovascular and metabolic diseases, today announced final results from the Phase 2 ANT-005 study with its novel investigational anticoagulant abelacimab. Published today in the New England Journal of Medicine,1 and simultaneously presented as a late breaker at the International Society of Thrombosis and Haemostasis (ISTH) 2021 Congress, the data showed that a single postoperative dose of abelacimab reduced the rate of venous thromboembolism (VTE) by ~80% compared to enoxaparin (a commonly used low molecular weight heparin), following elective total knee arthroplasty, the gold standard setting for potential new anticoagulants to demonstrate efficacy.

In this parallel group study, 412 participants were randomly assigned to one of three single postoperative intravenous doses of abelacimab (150mg, 75mg or 30mg) in a blinded fashion or open-label standard of care enoxaparin given subcutaneously 40mg once daily for approximately 10 days after surgery. The primary composite efficacy outcome which included deep vein thrombosis detected by venography of the operated leg and documented symptomatic VTE events occurred in4%, 5% and 13% of patients in the 150mg, 75mg and 30mg abelacimab groups respectively, compared with 22% of patients in the enoxaparin group. The 75mg and 150mg abelacimab regimens were both statistically superiorto enoxaparin(p<0.001) while the 30mg dose was non-inferior. Abelacimab was well tolerated with no safety signals and bleeding was insignificant in both study arms.

"The results of this study provide exciting new evidence that inhibition of Factor XI appears an effective way to reduce the risk of pathological thrombosis in this case, with a single post-operative dose of abelacimab. The data highlight the potential of this new approach in other clinical settings where the unmet clinical need is high," observed JeffreyI. Weitz, MD, Professor at McMaster University, Hamilton, Ontario, and one of the study authors.

Abelacimab is a highly selective, fully human monoclonal antibody with novel dual activity against both Factor XI and its activated form, Factor XIa, achieving profound Factor XI suppression for up to 30 days following a single intravenous or subcutaneous dose.1,2

Beyond the compelling efficacy data shown in this study, Anthos' vision in developing abelacimab is to achieve 'hemostasis-sparing' anticoagulation: effective protection from thromboembolic events with a reduced risk of clinically significant bleeding. According to a recently described model of the coagulation cascade,3 Factor XI plays an important role in the development of pathological thrombosis but is hypothesized to play only a minimal role in physiological hemostasis. Factor XI inhibition thus provides a potentially significant opportunity to pharmacologically 'uncouple' the two pathways.

Dan Bloomfield, MD, Chief Medical Officer at Anthos Therapeutics, explained: "All current anticoagulants including direct oral anticoagulants (DOACs) impact physiological hemostasis as well as pathological thrombosis due to their action on the 'common pathway' of the coagulation cascade, thus carrying a well-documented bleeding risk which may be even greater in the real world than in clinical trials.4,5 Fear of bleeding commonly deters prescribers and patients from pursuing optimal anticoagulation6-8soour aim in developing abelacimab is to address this major unmet need." The ongoing Phase 2 ANT-006 study (AZALEA-TIMI 71), investigating long-term once-monthly subcutaneous administration of abelacimab for stroke prevention in patients with atrial fibrillation, is expected to provide insight on the bleeding risk with abelacimab compared to a commonly used DOAC.

Anthos Therapeutics' Chief Executive Officer, John Glasspool, commented: "More than 1 in 4 people worldwide continue to die from thromboembolic events and yet 40-50% of high-risk individuals fail to receive optimal anticoagulation, mainly due to the prevailing fear of bleeding. Factor XI inhibition may provide a paradigm shift towards safer anticoagulation that inspires greater confidence among prescribers and patients." Mr. Glasspool added: "I am proud of the progress we have made to address unmet needs in high-risk cardiovascular and metabolic conditions since we launched two years ago with investment from Blackstone Life Sciences. The efficacy findings announced today represent the first major milestone in our development plans for abelacimab."

ENDS

1. Verhamme P et al. New Engl J Med 2021, in press2. Yi BA et al. ISTH 2021 poster PB00773. Hsu C et al. J Am Coll Cardiol 2021, in press4. Buderi R et al. ISTH 2021 poster PB00475. Fox, KAA et al. BMJ Open 2017; Dec 21;7(12):e017157 6. Hsu JC et al. JAMA Cardiol. 2016; 1: 5562.7. Piccini JP et al. Circulation. 2019; 139:14971506.8. Cohen AT et al. Lancet 2008; 2;371(9610):387-94

ABOUT ANTHOS THERAPEUTICSAnthos Therapeutics is a clinical-stage biopharmaceutical company focused on the development and commercialization of genetically and pharmacologically validated innovative therapies to advance care for people living with cardiovascular and metabolic (CVM) diseases. Anthos Therapeutics aims to combine the agility of a biotech with the rigor of a large pharmaceutical company.Anthos Therapeutics was launched by Blackstone Life Sciences in 2019.

For more information: https://www.anthostherapeutics.com/

About Blackstone Life SciencesBlackstone Life Sciences is an industry-leading private investment platform with capabilities to invest across the life cycle of companies and products within the key life science sectors. By combining scale investments and hands-on operational leadership, Blackstone Life Sciences helps bring to market promising new medicines that improve patients' lives. More information is provided athttps://www.blackstone.com/our-businesses/life-sciences/.

SOURCE: Anthos Therapeutics

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Tech news: Soon you will be able to stay young forever By Louis Fourie Jul 19 – IOL

Posted: July 21, 2021 at 2:20 am

Louis Fourie

ALTHOUGH the pharmaceutical industry is constantly evolving and new therapeutic approaches are being developed, one aspect has not changed: the use of small, synthetic molecules, which still account for 90 percent of the therapeutics on the pharmaceutical market. Some of the top-selling drugs are small-molecule drugs.

Small-molecule drugs

A small-molecule drug is an organic compound of low molecular weight (less than 900 Daltons or 1,49449-21 grams) and the size of about one nanometre capable of modulating biochemical processes to diagnose, treat or prevent diseases.

Because of their low molecular weight, small-molecule drugs have some definite advantages as therapeutics, because most can be administered orally and can pass through cell membranes to reach intracellular targets. Once inside the cells, they can be designed to engage biological targets, such as proteins, by various modes of action. Their distribution can also be customised, for example, to allow for systemic exposure or to destroy cancer cells. Therefore, many targeted therapies today are small-molecule drugs made from synthetic chemical reactions. However, they are also used in pesticides and in many other roles.

One well-known small-molecule drug is aspirin, which has been with us since 1899. Currently, the world consumes about 40000 tons of aspirin every year for a range of indications, such as cardiovascular health, Alzheimers disease, cancer treatment, pulmonary diseases, and everyday aches and pains. Another classic example is the drug penicillin, which successfully reduced the death rate caused by bacterial-related pneumonia to less than 1 percent during World War II.

Although small-molecule drugs have dominated the pharmaceutical industry since the beginning of modern medicine, it seems as though major developments are now happening in biologics, despite their excessive cost. RNA interference and CRISPR-Cas9, for example, are exciting new gene-editing tools.

But it is not the end of small-molecule medicine. Recent discoveries of small molecules that can modulate protein-protein interactions have created renewed interest in and utilities for small-molecule drugs for many diseases.Furthermore, the ability to design small molecules that can interact with and modulate RNA could create new opportunities for targeting challenging disease pathways.

An anti-ageing drug

Although with us for many years, the rapid advancement of biopharmaceutical research and technology opens up many opportunities for inventive and ingenious approaches to developing small-molecule drugs. We have therefore in recent years seen that significant advancements in structure-based design and imaging, together with automation, artificial intelligence and machine learning, have become important enablers to expedite research and enhance the success rate of small-molecule-led optimisation.

One of these innovative small-molecule drugs that could delay ageing is being tested by the US Militarys Special Operations Command (Socom), the organisation that controls the USs Special Operations forces. The anti-ageing pill comprises a human performance small molecule in the form of a nutraceutical with the aim of improving performance characteristics such as endurance and faster recovery from injuries, which typically declines with age.

Socom is working with the private biotech laboratory Metro International Biotech (MetroBiotech) on the development of an anti-ageing pill based on a human performance small molecule.

MetroBiotech is an offshoot of David Sinclairs Harvard University Medical School laboratory. The first-in-class small molecule on which they are working is Nicotinamide Mononucleotide (NMN), which MetroBiotech describes on their website as an enhancer that leverages the nicotinamide adenine dinucleotide (NAD+) cycle that is critically important to the function of all living cells and also to treat rare mitochondrial diseases and other medical conditions. These rare mitochondrial diseases often have serious effects on skeletal and cardiac muscle, as well as the central nervous system.

Increased NAD+ levels have been shown to induce mitochondrial biogenesis and enhance natural pathways (for example, sirtuins a family of dormant proteins found in all living beings) that are key to improving mitochondrial health. Mitochondria are cell parts (organelles) that produce energy for the cell in the form of a chemical called adenosine triphosphate (ATP). Cells need ATP to function properly, and NAD+ is a cofactor required for the enzymatic processes that generate energy within the cell through the continuous production of ATP inside the mitochondria.

Research has demonstrated the broad therapeutic potential of increasing NAD+ levels to preserve health and normal metabolism. It increases mitochondrial health and longevity, rejuvenates stem cells and provides neuroprotection. In general, it improves the health of most organs such as the brain (neurodegeneration), heart (inflammation, cardio protection), liver fatty acid oxidation, gluconeogenesis or regeneration), pancreas (insulin secretion), and skeletal muscles (insulin sensitivity, fatty acid oxidation) and white adipose tissue or white fat (lipogenesis).

Ageing and certain diseases, such as mitochondrial dysfunction, inflammation and other associated diseases, cause a decline in the NAD+ levels in humans, with serious consequences with regard to energy, performance and endurance. Treating people with NAD+ could thus slow the degenerative effects of ageing, prevent the onset of injury and thus allow people, according to MetroBiotech, to lead longer and healthier lives.

Several studies have been published in respected journals indicating how supplementation with a NAD precursor delays motor neuron degeneration, decreases markers of neuroinflammation in the spinal cord, improves blood flow, heart pathology, and musculoskeletal endurance, slows Alzheimers, improves energy metabolism, insulin sensitivity and plasma lipid profile, reverses retinal degeneration, mitochondrial biogenesis in skeletal muscle, and prevents noise-induced hearing loss and spiral ganglion neuron degeneration after noise exposure.

Since the small-molecule drug is a nutraceutical, a dietary supplement or food containing health-giving additive with medicinal benefit, it is not regulated by the US Food and Drug Administration and is therefore exempt from the rigorous standards regulating prescription drugs. It seems that MetroBiotech is following the nutraceutical route and not that of a prescription drug, because ageing is not yet itself a diagnosable disease to be treated by a prescription. Still, Socom have finished pre-clinical safety and dosing studies, and will soon start performance testing of the anti-ageing pill in clinical trials.

The thinking behind the anti-ageing pill is to address the cause of mitochondrial diseases and cure them all at once instead of the current repetitious and often futile one-by-one approach. According to MetroBiotech, its technology also supports key organ functions and could slow neurodegeneration, decrease inflammation in the body, increase cardio protection and improve sleep. NAD+ can apparently also reduce the functional effects of ageing on the human body, such as speed and reaction time.

A pipedream or a breakthrough?

For as long as humans have existed, they have been on a quest for a magic substance that would extend life or even bestow immortality. Over the years, the medieval alchemists and many others pursued the elixir of life. The slowing or prevention of ageing has therefore long been the Holy Grail of medicine, but has largely evaded us until now, except for a few studies in their infancy, such as Israeli oxygen therapy to increase telomere length and decrease the number of senescent cells (geriatric cells that can no longer divide).

The anti-ageing pill of MetroBiotech that slows down ageing and keeps you young may therefore sound like a sci-fi story. We will thus have to wait for the clinical trials to prove that NAD+ can indeed do what MetroBiotech is claiming it can do. However, the US military has spent serious money on this nutraceutical about R41 million since 2018. It must thus indeed be a promising drug that could become a game-changer in slowing the effects of ageing and preventing the onset of injuries. Despite being a controversial figure and often criticised, Sinclair may indeed be on the verge of a public health breakthrough that we have never seen before.

See you at our 150-year party!

Professor Louis CH Fourie is a technology strategist.

*The views expressed here are not necessarily those of IOL or of title sites.

BUSINESS REPORT ONLINE

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Matrix Meats Adds to Team as Interest in Cultivated Meat Grows – PRNewswire

Posted: July 21, 2021 at 2:18 am

COLUMBUS, Ohio, July 20, 2021 /PRNewswire/ --Matrix Meats, Inc., the leading developer of nanofiber scaffolds manufactured to support the production of clean cultivated meat products,is entering a new phase of growth with the addition of five new team members. The hiring surge marks an important milestone for Matrix Meats, which achieved record success in its oversubscribed seed stage round late last year.

The new employees are spread across various company divisions, but each play a critical role in advancing Matrix Meats' innovative manufacturing and strategic partnership goals.

Devan Ohst is heading Matrix Meats' laboratory as the new Director of Research and Development. Transitioning from his background in regenerative medicine and medical devices, he boasts an impressive rsum, with over eight years in advanced material engineering. Ohst will oversee Matrix Meats' technical operations, research activity, and act as a liaison for the company's partners.

Matrix Meats also welcomed Nichole Brown as the company's inaugural Director of Operations. Brown will be spearheading the company's growth strategy and structure as the cultivated meat sector continues to soar. Following 12 years in food and restaurant management, Brown has worked with both international franchises, such as Taco Bell, as well as burgeoning startups. She is a crucial component to furthering Matrix Meats' leadership in groundbreaking, ethical meat production, which is already solidified by 14 active development partnerships with cultivated meat producers in seven countries.

Kevin Doand Mitch Kahn join Matrix Meats as Project Engineers. Do brings a precise eye for production to the company, using his passion for sustainability and climate change to scale up Matrix Meats' scaffolding development. He was an obvious choice for Matrix Meats following his five-month internship under the company's Director of Research and Development, Devan Ohst. Bringing six years of hands-on medical and laboratory experience to Matrix Meats, Kahn harnesses his background in biomedical engineering to put nanofiber scaffolds through intensive, iterative processes. His expertise in materials science and polymer replacement have equipped him with the skills to assess viable candidates for scaffold creation.

Hardy Castada, PhDwas inspired by the burgeoning plant-based meat movement when he joined Matrix Meats as a Senior Food Scientist. Castada will be utilizing his experience in food science and chemistry to facilitate high quality, safety, and nutrition standards. In his previous role at the Ohio State University Department of Food Science and Technology, Castada spearheaded several innovative food and biomedical projects that were widely published in peer-reviewed journals.

"As with any startup, Matrix Meats has been operating with a lean team since our launch in 2019. We were overwhelmed by the fervent interest and positive attention received during last year's seed stage round, and it gave us the confidence to grow our team and support our position in cultivated meat production," said Matrix Meats CEO Eric Jenkusky. "In the short time they've been on board, Devan, Nichole, Kevin, Mitch and Hardy have already been tremendous assets to the company and ardent believers in the global impact of cellular agriculture."

In conjunction with Matrix Meat's numerous team additions, the company also promoted Zac Graber from Operations Manager to Director of Business Development. Graber has been with Matrix Meats since the beginning of 2020, becoming the third employee to join the rapidly growing startup.

Matrix Meats completed its seed stage round in December of 2020 and achieved oversubscribed investment from companies such as Unovis Asset Management, CPT Capital, Siddhi Capital and Clear Current Capital.

About Matrix Meats, Inc.

Matrix Meats, Inc., based in Columbus, Ohio, is a designer and manufacturer of the foremost nano-fiber scaffolds to enable the production of clean, healthy, and environmentally friendly cultured meat to ethically feed the world. Further information: http://www.matrixmeats.com

Press ContactErin MandzikJConnelly862-246-9911[emailprotected]

SOURCE Matrix Meats

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FDA gives speedy review to Bayer’s Parkinson’s stem cell therapy – – pharmaphorum

Posted: July 21, 2021 at 2:18 am

Bayer subsidiary BlueRock Therapeutics has been granted a fast-track review by the FDA for DA01, its stem cell-based therapy for Parkinsons disease which is currently in early-stage clinical testing.

The FDA designation allows for benefits such as more frequent meetings and communication with the regulator during clinical development, and a truncated six-month review time.

Those are all considerations for the future as the first patients only started to be treated with DA01 in a phase 1 trial aimed primarily at showing the safety of the therapy, which is trying to replenish the dopaminergic neurons that progressively die away in Parkinsons and lead to slow, laboured movement, tremors and other symptoms.

The therapy involves implantation of dopamine-producing cells under general anaesthesia into a part of the brain called the putamen, which is particularly affected by neuron loss in Parkinsons and is responsible for regulating movement as well as some types of learning.

Patients take immune-suppressing drugs to prevent their body rejecting the transplanted cells, and the safety and tolerability of the procedure as well as the ability of the transplant to survive will be monitored for two years.

BlueRock is also hoping to demonstrate some evidence of efficacy, and will look at clinical measures such as motor function over the same time period. It is the first trial in the US to study pluripotent stem cell-derived dopaminergic neurons in patients with Parkinsons, according to the company.

The first patient in the trial, which will eventually enrol 10 subjects with advanced Parkinsons, was treated at Memorial Sloan Kettering Cancer Centre in June, and others will be recruited at Weill Cornell Medical Centre, the University of California, Irvine, and the University of Toronto.

Our objective is to use authentic cells, to have them integrate entirely into the brain and restore lost physiologic function, said BlueRock chief executive Emile Nuwaysir, as the first patient was treated.

If successful, this new therapeutic modality could have implications for the Parkinsons community and beyond, he added.

Bayer took control of BlueRock in 2019, three years after backing the formation of the company as joint venture with private equity group Versant, in a deal that valued the biotech at $1 billion.

DA01 is Bluerocks lead cell therapy programme, but the company is also working on treatments for other neurological disorders, degenerative heart disease, and autoimmune disorders.

Bayer is also developing a gene therapy for Parkinsons originated by Asklepios Bio (AskBio), which it acquired for $2 billion upfront last year with another $2 billion tied to milestones, and has pledged to make cell and gene therapies a pillar of its R&D strategy.

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Stem cell model reveals how COVID-19 can infect the brain – Study Finds

Posted: July 21, 2021 at 2:18 am

SAN DIEGO, Calif. Can COVID-19 really make its way into the human brain? Its a question thats been on scientists minds for over a year. Now, a new study reveals that it is indeed possible for SARS-CoV-2 to infect certain brain cells. The revelation could go a long way to explaining the seemingly never-ending symptoms of long COVID.

Researchers from the University of California San Diego School of Medicine and Rady Childrens Institute for Genomic Medicine used a sophisticated stem cell model of brain cells and human neurons to make this discovery.

Clinical and epidemiological observations suggest that the brain can become involved in SARS-CoV-2 infection, says senior author and professor of neuroscience Joseph Gleeson, MD, in a university release.

The prospect of COVID19-induced brain damage has become a primary concern in cases of long COVID, but human neurons in culture are not susceptible to infection. Prior publications suggest that the cells that make the spinal fluid could become infected with SARS-CoV-2, but other routes of entry seemed likely.

A team of neuroscientists and infectious disease specialists first confirmed that human neural cells are actually resistant to the virus causing COVID-19. Unfortunately, their findings also reveal that other types of brain cells may be acting as a Trojan horse for coronavirus.

Study authors explain that pericytes are specialized cells that wrap themselves around blood vessels. These cells also carry the SARS-CoV2 receptor. Using a 3D neural cell culture, researchers added these pericytes to the mix to create assembloids a realistic model of the human body. The assembloids contained several types of brain cells, in addition to the pericytes.

After exposing this model to coronavirus, they discovered SARS-CoV-2 can infect pericytes and other cells. These brain cells then acted as local factories for the virus to multiply and spread.

Moreover, scientists found that once the virus starts to spread, it attacks astrocytes, a group of supporting cells in the body. The results show that one potential route for COVID entering the brain involves blood vessels carrying coronavirus-infected pericytes into the brain. From there the virus attacks other brain cells vulnerable to infection.

Alternatively, the infected pericytes could lead to inflammation of the blood vessels, followed by clotting, stroke or hemorrhages, complications that are observed in many patients with SARS-CoV-2 who are hospitalized in intensive care units, Gleeson adds.

Moving forward, researchers plan to build new assembloids that include blood vessels capable of pumping blood. This will provide an even better simulation of whats happening in the brain and how COVID-19 may be attacking people over the long haul.

The findings appear in the journal Nature Medicine.

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Introducing the 3D bioprinted neural tissues with the potential to ‘cure’ human paralysis – 3D Printing Industry

Posted: July 21, 2021 at 2:18 am

Researchers at the Chinese Academy of Sciences and University of Science and Technology of China have devised a novel bioprinting-based method of curing previously untreatable spinal cord injuries.

Using a custom bio-ink, the Chinese team have managed to 3D bioprint neural stem cell-loaded tissues capable of carrying instructions via impulses from the brain, much like those seen in living organisms. Once implanted into disabled rats, the scaffolds have shown the ability to restore movement in paralyzed limbs, and the scientists now believe their approach could find human applications in future.

There is no known effective cure for spinal cord injury, Zhijun Zhang, a nanobiomedical engineer at the Chinese Academy of Sciences told the Scientist. The 3D bioprinting strategy weve developed, may represent a general and versatile strategy for rapid and precise engineering of the central nervous system (CNS), and other neuronal tissues for regenerative medicine.

The SCI injury conundrum

A Spinal Cord Injury or SCI is a blanket term used to describe any damage caused to the bundle of cells and nerves that send signals to and from the brain along the human spinal cord. While the damage itself can be caused either by direct injury, or from bruising to the surrounding vertebrae, the result is often the same: a partial or complete loss of sensory and locomotor function below the affected area.

While theres no current known cure for SCI, a number of promising cell-based therapies are now being developed, with the regeneration of functional neurons seen as central to their future success. In effect, such approaches involve re-establishing links between neurons throughout the injured area in order to restore nerve functionality, but repairing damaged cells continues to be problematic.

Where neural stem cells have previously been implanted into SCI sites, theyve also shown poor viability and uncontrolled differentiation, leading to low therapeutic efficacy. More recent efforts have seen scientists bioprint cell-loaded scaffolds, capable of creating a suitable microenvironment in which neurons can flourish, yet this has raised further issues around printability and initiating cellular interaction.

To get around these problems, the Chinese researchers have now developed a novel bio-ink that gels together at body temperature to prevent neurons from differentiating into cells that dont produce electrical impulses, and can be 3D bioprinted into scaffolds that not only mimic the white matter appearance of the spine, but encourage cell-to-cell interactions.

A paralysis cure in-action

To begin with, Zhang and his team formulated their bio-ink from natural chitosan sugars, as well as a mixture of hyaluronic acids and matrigel, before combining them with rat neural stem cells. The scientists then used a BioScaffolder 3D bioprinter to deposit the resulting concoction into cell-laden scaffolds, which were later stored in culture plates for further testing.

Prior to their implantation, the teams different samples were incubated for three, five and seven days respectively, during which they proliferated and formed connections. Interestingly though, the researchers found that the higher the concentration of hyaluronic acid, the lower levels of interaction they observed, showing that their bio-ink can be tweaked to achieve desired tissue characteristics.

When injected into paraplegic lab rats, the scaffolds exhibited a cell viability of 95% while promoting neuron regeneration to the point that they enabled the rats to regain control over their hind legs. Over a 12-week observation period, the treated animals also showed a revived ability to move their hips, knees and ankles without support, and kick pressure sensors with markedly enhanced muscle strength.

As a result, the scientists have concluded that their approach offers a versatile and powerful platform for building precisely-controlled complex neural tissues with potential human applications, although they concede that more precise regulation of cell differentiation will be needed to achieve this, in addition to further testing on more clinically-relevant injury models.

Overall, this study clearly demonstrated for the first time the feasibility of the 3D bioprinted neural stem cell-laden scaffolds for SCI repair in-vivo, concluded the team in their paper, which, we expect, may move toward clinical applications in the neural tissue engineering, such as SCI and other regenerative medicine fields in the near future.

3D bioprinting in CNS treatments

Thanks to constant advances in flexible electronics and 3D bioprinting technologies, its now becoming increasingly possible to produce neural implants, with the potential to treat complex CNS injuries. Last year, a project started at TU Dresden led to the creation of 3D printed neural implants, capable of linking the human brain to computers as a means of treating neurological conditions such as paralysis.

In a similar study, engineering firm Renishaw has worked with pharmaceuticals expert Herantis Pharma to assess the performance of its 3D printed neuroinfuse drug delivery device. Designed to deliver intermittent infusions into the parenchyma, an organs functional tissue, the platform could be used as a future treatment for Parkinsons disease.

With regards to treating spinal injuries specifically, researchers at the University of California San Diego have also managed to repair spinal cord injuries in rats. By implanting 3D printed two-millimeter-wide grafts into test subjects, the team have been able to facilitate neural stem cell growth, restore nerve connections and ultimately help recover limb functionality in rodent test subjects.

The researchers findings are detailed in their paper titled 3D bioprinted neural tissue constructs for spinal cord injury repair. The study was co-authored by Xiaoyun Liu, Mingming Hao, Zhongjin Chen, Ting Zhang, Jie Huang, Jianwu Dai and Zhijun Zhang.

The nominations for the 2021 3D Printing Industry Awards are now open. Who do you think should make the shortlists for this years show? Have your say now.

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Featured image shows the researchers 3D bioprinted scaffolds after 7 and 21 days culturing. Images via the Biomaterials journal.

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From broken legs to a punky pancreas, here’s what a night in Fargo’s animal ER is like – INFORUM

Posted: July 21, 2021 at 2:09 am

The adorable Cavalier King Charles mix puppy is acting very unpuppy-like: He is lethargic and doesn't have an appetite.

Veterinary technician Carlene Ternes holds the tiny, white-and-ginger puppy up into the air and gazes at his fuzzy, teddy-bear face.

Hes not eating, but his tail works, she reports, grinning.

Logan is just one of the many patients spending Friday night at the Red River Animal Emergency Hospital and Referral Center. The 24/7 emergency veterinary hospital the only one in North Dakota or western Minnesota treated somewhere between 18,000 and 20,000 patients last year, according to Dr. Andy Carver, the hospital's director and the first board-certified specialist in emergency and critical care in North Dakota.

In fact, the 11,000-square-foot hospital is so busy that plans are underway to add a $6 million, 17,000-square-foot addition to the building at 4491 23rd Ave. S., Fargo. The hospital will also add 20 staff, including specialists in internal medicine, oncology and surgery as well as critical care veterinary technicians, says Bill Walker, hospital administrator. A groundbreaking to commemorate the new construction will be held at 1 p.m., Thursday at the hospital.

As a pet owner who has brought my own dogs into the ER several times, I've often wondered what goes on behind closed doors at an emergency veterinary hospital. Now, thanks to access granted by Carver and Bill Walker, the hospital administrator for the RRAEHCC, I know.

Within four hours there, I was exhausted. In that time, I saw dozens of animals, including a ferret named Bandit who ingested an Advil, a green conure with fluid build-up in its abdomen and a very large dog named Elvis who jumped out of a moving car.

I also saw a bunch of hard-working vets and supporting staff who impressed me with their professionalism, teamwork and stamina.

Veterinary staff Alex Wong (left) and Amanda Fish remove the oxygen tube from a Basset hound's nose as they prepare him to go home. / By Tammy Swift

I can't stop comparing the facility to a human hospital.

There's a posh waiting room, a big reception desk and a slew of exam rooms.

The waiting room of the Red River Animal Emergency Hospital was empty most of last year when COVID-19 made it impossible for owners to wait for their pets as they were treated. As in many other veterinary clinics, owners needed to wait in their cars until their pets could go home. / By Tammy Swift

In the back, there's a glass-enclosed recovery unit and ICU units outfitted with oxygen and temperature control. There's a triage area, a blood bank, operating rooms, an x-ray room and a room that contains a human-grade CT scanner. RRAEHCC even has a mechanical ventilator.

The hospital has several pieces of human-grade medical equipment, including this CT scanner. Tammy Swift / The Forum

Carlene Ternes was instrumental in setting up the hospital's blood bank, which is now regularly restocked by more than 30 dogs and 15 cats. The pets receive treats and toys for their life-giving gift. / By Tammy Swift

Vet techs like Ternes marvel over how much the hospital has grown in her nine years here. When she started, the clinic was in a single suite on Oak Manor Drive South. In the early days, only one or two vet techs would work each night and there would be evenings when no patients were admitted.

In 2018, the hospital moved into the site of the former Golden Corral. Their new space can accommodate up to 38 animals at once and it frequently does. So much so that they have had to initiate a priority system. Once the hospital reaches Level 3 capacity, they will only accept the most critical cases. Owners whose animals have a less-serious ailment, such as an ear infection, are encouraged to monitor their pets closely and get them to their primary providers as soon as possible.

Vet tech Kailley Martinson holds a cat still while Molly Moritz draws a blood sample from its jugular vein, a commonly used venipuncture site for felines. / By Tammy Swift

Talk to staff and they share many theories as to the hospital's popularity. Carver attributes it to a growing regional awareness that the facility exists. Walker attributes it to the RRAEHRC's excellent reputation. Still others link it to the metro area's vigorous growth.

Another factor: People nowadays are more willing to pamper their pets. "More people are willing to spend money. They're family members now," Ternes says.

Carver says he hates turning owners away, as he knows how upsetting it is when one's pet suddenly gets sick. Even so, it has become necessary in a facility with limited room and staff. "I think its tough for people to realize the whole art and science behind needing to triage things and prioritize care," he says. "Everyone who comes there truly feels its an emergency. They see a quiet parking lot or lobby and get frustrated. I wish they understood ... priority has to be on caring for the sickest ones. We're not just being lazy and hanging around behind closed doors."

Just as I arrive, Carver emerges from surgery. Hes just operated on a 7-pound Yorkie to remove foreign objects from the puppys stomach.

The dogs owner brought him in after noticing the little guy was shaky and uncomfortable.

Carver soon found the problem. Or, actually, a whole wad of problems. The dog had ingested enough hair ties to outfit a drill team.

Carver removed a wad as big as a newborn's fist, along with another oddity a single jalapeo.

Any veterinary surgeon worth their scalpel has found a grab bag of goodies in the digestive systems of pets, from rocks, pantyhose and socks to children's toys, pacifiers, tinsel and pencil erasers.

While a "dog eat sock" world might sometime be caused by a nutritional deficiency or anxiety, Carver says most cases stem from pets being playful and inquisitive. "They're curious about things and they may like the mouth-feel and, without thinking about it, they may wind up swallowing it," he says.

Carver moves on to perform an ultrasound on a small dog.

The source of the dogs pain is soon apparent. A healthy pancreas is less than one centimeter thick and is hard to find on an ultrasound, Carver says. But this dogs pancreas is a billowy mass, filling the upper one-fourth of the ultrasound screen.

Dr. Andy Carver (left) performs an ultrasound on a dog with pancreatitis, while Dr. Anna Stansbery assists.

The little guy has a taste for eating trash, which explains the pancreatitis, Carver says. The pancreas produces enzymes to assist in food digestion and hormones to regulate blood sugar or glucose metabolism. When it isn't working right, it activates those enzymes prematurely, so they actually start digesting the pancreas itself.

Some bouts of pancreatitis are mild and can be treated at home. But some cases are severe and life-threatening; those animals may wind up in ICU, hooked up to feeding tubes and treated for multiple related problems.

Carver says this dog's pancreatitis is in the "moderate severity" range. The dog will make it, but his garbage-foraging days are over.

The ultrasound has helped RRAEHRC staff diagnose problems with greater efficiency and accuracy, Carver says. Before they had the machine, they relied on a patients bloodwork, which would have shown elevated liver enzymes. It could have easily been misdiagnosed as liver disease. This way, the pup will be on the road to recovery much more quickly and his owners will not have to spend more time and money trying to get to the real problem.

When people are looking for highly specialized medical care, many will travel to Mayo Clinic in Rochester, Minn. But when Mayo physicians and Minneapolis-area pet owners seek highly specialized care for their pets, many will travel to Fargo.

Dr. Ashlyn Kuklock performs emergency surgery on a canine patient while Kailley Martinson (center) and Rachel Manning assist. / By Tammy Swift

As the RRAEHRC has the only dialysis machine for animals between Seattle and Chicago, the University of Minnesota Veterinary Hospital routinely refers dogs and cats with failing kidneys here.

A recent example: After a referral from the University of Minnesota, Carver and Dr. Sam Wigglesworth, the second criticalist to join the RRAEHCC staff, performed a therapeutic plasma exchange on a golden doodle, who had managed to eat an entire bottle of ibuprofen.

The animal was in acute kidney failure, so the two vets performed a therapeutic plasma exchange, a process in which they used dialysis to separate the cells from the liquid part of the blood, then discarded the liquid part, which contained the toxins. They then replaced that fluid with donor fluids.

"The dog did great and went home with no symptoms," Carver says.

In another case, a Mayo doctor's dog, Ezra, was on dialysis at the Fargo hospital for weeks, Walker says. A little later, the hospital again received a call asking if they could keep Ezra for 10 days. Staffers were alarmed: Was Ezra sick again? Oh no, the doctor responded. He planned to go on vacation and didn't trust anyone else to watch his dog.

One of the more serious cases of the day involved a farm dog hit by a car. Tex's owner had driven two-and-a-half hours from Devils Lake to bring him here. She heard this is the best place, says Dr. Anna Stansbery, who is overseeing his case.

Veterinary technician Shelby Feickert comforts Tex, a cattle dog who suffered a severe compound fracture after being hit by a vehicle. / By Tammy Swift

Tex is a handsome Australian shepherd with long, russet hair. His snout is enclosed in a muzzle and his breathing is shallow and fast. His amber eyes are wide open, but dont seem to focus on anything. He is pretty shocky, a vet tech remarks.

Upon seeing his injury, its easy to see why. Tex's left front leg is broken so badly that splinters of bone peek through the skin. The limb bends at an unsettling angle.

Pain relief is first priority. While several techs stroke to calm him, Stansbery calls for a shot of methadone a quick, effective painkiller for animals.

With Tex's pain managed, Stansbery analyzes the best way to proceed. The owner could take the dog to the University of Minnesota Veterinary Medical Center, where they could perform a complex surgery in attempts to reconstruct the leg. But it would cost at least $5,000 and contain no guarantee that the leg would work.

Tex is 12 years old. Most dogs adapt well to three-legged life, especially smart, athletic herding dogs, Stansbery explains. At the same time, the loss of a front limb is harder, as the front legs bear more weight than the hind legs.

She discusses the options with the owner, who decides it is best to amputate.

When Tex awakes, he will be a three-legged dog. But, as Stansbery points out, our pets don't wrestle with the same pangs of self-pity that we do.

"They don't wake up and say, 'Poor me,'" Stansbery says. "It's more like, 'What can I pee on and what's for dinner?'"

Even in this adrenaline-charged atmosphere, I spot many little acts of compassion.

Sarah DeCrans and her French bulldog, Nigel, provide a morale-boosting visit to vet tech Chris Knutson. / By Tammy Swift

One chihuahua has been crying most of the night. A veterinary assistant walks over and strokes its tiny nose, which immediately calms the dog. Later, I see another vet assistant cuddle a tiny calico kitten simply because "he's so darned cute."

A veterinary assistant reaches into the kennel of an ailing Chihuahua to comfort her by stroking her nose. Tammy Swift / The Forum

This tiny calico kitten looks particularly tiny and vulnerable in his kennel, but is comforted by piles of blankets and the snuggles of veterinary staff. / By Tammy Swift

Out in the triage area, another puppy is having a bad day. Freia is a baby black lab who had a run-in with a lawn mower. Its one of the trials of puppyhood: Learning how to co-exist amid all the shiny, cleverly-hidden dangers in the human world.

Dr. Ashlyn Kuklock carefully examines the afflicted foot to make sure Freia only has soft-tissue damage. But first, she caves to the pup's sweet charm, cradling the little Lab's head in her hands to plant a masked kiss to Freias soft, furry forehead. The puppys tail whips back and forth hopefully.

Experienced vet tech Carlene Ternes knows one of the perks of the job is the ability to snuggle and comfort adorable pets like Logan, a puppy admitted for lethargy and poor appetite. / By Tammy Swift

Its a testimony to puppy optimism that even when they hurt, most still find a reason to wag their tails.

In a quiet area on the south end of the treatment area, a lone veterinary technician works over a gray cat. I'm about to ask what he's in for before realizing he has been euthanized. She is cutting off the bandage that secured his IV; theres no need for that now. Black ink prints of his paws have been made on white cards and rest by his body. He lies atop a cuddly fleece blanket. For some reason, I am glad for the blanket, this last offering of comfort before he crossed the rainbow bridge.

Emergency pet hospitals often must perform euthanizations when an animal becomes gravely ill or critically injured outside of their regular veterinarian's office hours. Grieving owners are able to say goodbye to their pets and grieve in the privacy of a special "comfort room," which features overstuffed furniture and displays this comforting passage from "The Rainbow Bridge." Tammy Swift / The Forum

It is a sad, quiet moment.

Its a question I ask several people who work there. How can these animal-loving professionals handle the euthanizations? Their answers reflect a combination of professional reserve and compassion. They tell me that it is easier for them to remain objective than it is for a grief-stricken owner. They also talk of mercy, how they see this as a way to relieve an animal whose body is racked by pain, severe illness or the ravages of old age.

But after saying all this, a couple of vet techs admit it is the least favorite part of their job.

This tiny calico kitten looks particularly tiny and vulnerable in his kennel, but is comforted by piles of blankets and the snuggles of veterinary staff. / By Tammy Swift

Walker says the team likes to focus on the the triumphs the dog that beat life-threatening sickness, the kitten saved by dialysis. "Compassion fatigue is very real in the veterinary business," he says. "So it's the good things, the ones that survive and beat the odds, that keep everyone going."

All of the veterinary staff are pet lovers, as illustrated by veterinary assistant Rachel Manning's "cat-too" of her two cats. / By Tammy Swift

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YOUR HEALTH: Finding cures by tracking cells – WQAD.com

Posted: July 21, 2021 at 2:06 am

Researchers are using cell tracking technology to uncover how diseases, like cancer, progress

PORTLAND, Ore. Each year, almost two million people will be diagnosed with cancer.

Researchers are trying to find news ways to track how cancers will grow, spread, and mutate.

One single cell can provide a slew of information on what's happening in the body.

"It allows us to actually isolate specific regions within a tumor and explore what are the various different cell types within those regions of the tumor because tumors have a lot of different cells doing a lot of different things," said Andrew Adey, Associate Professor at Oregon Health & Science University

The technique also allows the researchers to track where the cells are coming from so researchers can see how diseases progress and alter healthy tissue.

"That could lead to potential novel targets that could be used to develop drugs to specifically target those specific alterations that occur," Adey added.

It makes it possible to watch the disease at the molecular level and create a precise treatment for more personalized care.

Professor Adey says that this cell-tracking technique would be useful for other diseases besides cancer, including neurological diseases and diseases that affect the heart and blood vessel.

"With this newest technology, what we've been able to do is instead of just isolating these cells from a large piece of tissue, we can actually track where these cells are present within the tissue," Adey explained.

Non-invasive tracking of immune and stem cells were primarily intended for potential cancer therapy applications while tracking of cancer cells could further our understanding of cancer development and tumor metastasis.

"So, it gives us a really precise mapping of where these cells are derived from within that piece of tissue, which can give us insights into a lot of disease states where there's actually a spatial component."

Cell-based therapy holds great promise and has long been on the horizon of cancer treatment. Cell-based therapies offer the ability to non-invasively track the delivery of various therapeutic cells, like T cells and stem cells, to the tumor site, and if or how they spread.

But it's not just cancers.

"One of the things that we applied this technology to was in stroke, where there's a very strong spatial component at the site of the injury and then radiating out from it," said Adey.

"We're able to actually capture that spatial information radiating out from that site of injury with all of the different cell types that are present and how those are altered in different ways with relation to the injury site and the spatial position, he added.

Safety is a high concern for researchers in future clinical applications and the ideal imaging modality for tracking therapeutic cells in cancer patients requires the imaging tags to be non-toxic, biocompatible, and highly specific.

If this story has impacted your life or prompted you or someone you know to seek or change treatments, please let us know by contacting Jim Mertens at jim.mertens@wqad.comor Marjorie Bekaert Thomas at mthomas@ivanhoe.com.

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How the US Exported a Bloods and Crips Gang War to Belize – VICE

Posted: July 21, 2021 at 2:05 am

BELIZE CITY, BelizeA discarded bicycle lay on a dimly lit side street near a pool of blood, surrounded by around a dozen bullet shells in Belizes biggest city.

Local cops surveyed the scene, moving the body of 17-year-old Gerald Tillett Jr. into the back of a pickup truck as onlookers gawked at the most recent victim of a long-simmering Bloods and Crips gang war that started in the U.S.

In Belize City, Tillett Jr. was gangster royalty. Both his father and uncle, also murdered in 2016 and 2012 respectively, were leaders of an infamous Blood clique known as the George Street Gang, named for the street that traverses the rough-and-tumble Southside neighborhood where the gang is based.

Only a few blocks from where he grew up, Tillett Jr. was riding his bike on May 7 in hostile territory reportedly run by a rival Blood set known as the Taylor's Alley Gang when he was ambushed and shot to death.

Such gang violence has become all too common in Belize City, explained Police Senior Superintendent Gualberto Garcia, since the gangs started way back in the 1980s, when we started having the influx of deportees [from the U.S.], and they started the Crips and the Bloods.

As years progressed, these two gangs splintered, said Garcia. So, we have a very big number now, maybe 20 to 25 different gangs, scattered throughout the city, small factions with their own little affiliation to the Crips and the Bloods.

Now, Bloods fight Bloods and Crips fight Crips, with loyalty mostly boiling down to the block you were raised on, and longstanding beefs being handed down from generation to generation.

The murder of George Street Gang member Tillett Jr. was especially worrisome.

We are already expecting retaliation from his side, Garcia told VICE World News as he rode through the Southside in a police van.

It didn't take long.

Roughly 48 hours after Tillett Jr.'s murder, radio chatter alerted Garcia to shots fired on the corner of Church and George streetsonly a few blocks from where the teenager was murdered. Police arrived to a gruesome scene.

Blood-covered domino pieces lay strewn throughout a one-room hovel; one man dead, two others wounded, one of whom would die later at the hospital. Gunmen riding a motorbike had arrived at the small dwelling, well known locally as a place for dominoes betting games, and opened fire indiscriminately. As police quarantined the scene, family members of one of the men came to identify the body. They couldn't believe that 51-year-old Raymond Garcia, a successful bank manager and loving father, could be a victim of a gang war.

Garcia, no relation to the superintendent, had been the valedictorian of his class. He didn't have any gang affiliation. Days later his mother, Natividad Rita Garcia, told VICE World News that he had one vice: Dominoes.

He said, I love my dominos and that is a part of my life, said the elder Garcia, claiming she'd tried to get him to stop visiting the Southside domino spot off George Street. He has been playing in that area for quite some time, for many years before the guns ever started.

But after his death, she also heard the rumors of how his love of dominoes led to his death.

Those men had been playing dominoes with him for a very long time, but according to what I heard, one of the men, his children, are in the gangs, she said.

The rumor was that a man who frequented the domino games had several sons connected to a rival clique of the George Street Gang, but after the death of Tillett Jr., he hadn't come around, knowing that he and his sons could be targets. When they couldn't find the sons, they shot up the domino den even though the father wasn't there.

As Garcias yellow casket was lowered into a plot in a cemetery on the outskirts of Belize City a few days later, a family member placed a cross decorated with dominoes on top.

I couldn't believe that this would ever have happened to my family. I couldn't believe that this would happen to my son, she said. Not in the wildest of my dreams.

Belize is perhaps best known as a small picturesque tourism destination roughly the size of the U.S. state of New Hampshire, famed for its beautiful islands and coral reefs along the Caribbean coast, and its dense jungles and Mayan ruins inland. That contrast has also come to represent its racial diaspora, with more of an Afro-descendant Black population along the coast and an indigenous Mayan and Mestizo culture inland.

It stands out from other nations in mainland Central America as the only where English is the first language. Its large Black population is a lasting legacy of British colonization and the remnant of the slave trade that saw kidnapped Africans forced to work for the European settlers in the logwood industry. Belize only became fully independent from the United Kingdom in 1981 and had long been named British Honduras before changing its name in the 70s.

In 1961, a hurricane decimated the country leading to a large exodus of its inhabitants migrating to the United States, and by the end of the millennium, around 30 percent of Belizeans lived in the U.S. A large swath of them settled in California, and like many migrants who came from impoverished regions, a vulnerable subsection of that population became involved in crime.

While immigrants from other Spanish-speaking countries in the region became involved in Hispanic street gangs like the Latin Kings or the Mexican Mafia, the English-speaking Afro-descendant Belizeans who chose to enter the gang life mostly joined predominately Black gangs that sprung up in the late 1960s and 70s, like the Bloods and the Crips.

Soon after, the Bloods and Crips started appearing in Belize.

Behind the walls of the countrys central prison, Leslie Pipersburgh recalled the early days of the gangs in Belize.

Known on the streets as Pipe, the former Crip admitted he was an infamous person and had witnessed the rise of the gangs firsthand before going down for a double murder connected to a botched robbery in 2002.

The deportees, from that it started, and it never stopped. Just keep at retaliation, retaliation, retaliation. One after the other, said Pipe. So then other guys get deported, and that just strengthens it more and men adapted like cells, more and more. Then they start to learn about extortion, robberies, selling drugs. It just got out of hand from there.

Researchers have traced a small presence of Bloods and Crips in Belize to the deportation of members in the early 80s. But Pipe and numerous people interviewed by VICE World News recalled a boom in gang growth after the release of the 1988 film Colorsa cop drama directed by Dennis Hopper that follows two white police officers as they investigate the Bloods and Crips, along with a fictional multiracial gang, in South Central Los Angeles.

At the time, Colors made waves in the U.S., being released before gangster rap albums like N.W.A's Straight Outta Compton and preceding other L.A. street films like Boyz n the Hood and Menace II Society. The film also gained notoriety for using real gang members as extras in the film, and became especially controversial after a Crip murdered a Blood waiting in line to see the movie in Stockton, California.

In the soundtracks eponymous theme song, a bass-heavy Bloods and Crips anthem, Ice-T ominously raps:

Red or Blue, Cuz or Blood, it just don't matter.

Sucker die for your life when my shotgun scatters.

The gangs of L.A. will never die,

Just multiply...Colors

In Belize, that turn of phrase was prescient.

Although there may have been a few Bloods and Crips before, Pipe called the film the branch that spread like wildfire.

Growing up as kids, none of them claimed red nor blue. But when the movie came out, now everyone started to claim a color.

Around that time, the U.S. deported a Blood named Heathcliff Reyes and a Crip named Fredrick Lynch, aka Diggy Dap, who didn't get along.

These two guys were the leaders, said Pipe. They were cool to their own kind, but to their enemy, they got no love for their enemy.

Reyes founded a Blood clique near George Street, while Diggy Dap headed a Crips set on the other side of town near Pinks Alley, and that's how the war started.

That is where all the O.G's (Original Gangsters) came from that really know about gangs, said Pipe. Then another block started to copy them and claim the color red, and some claim the color blue, and it branched out. Then the war really started.

Belize City, and especially its ramshackle Southside neighborhood, is home to much of the country's impoverished parts of the Afro-descendant population. Its also where the majority of its gangs fight over turf. Although Belize only has a population of roughly 400,000 and Belize City is home to some 60,000 of those, its murder rate per capita often ranks as one of the highest in the world with the majority of killings happening in the Southside.

Pipe believed the rising murder rate was tied to a criminal code that has faded as more and more of the older generation were murdered, disappeared, or ended up in prison. Heathcliff Reyes would eventually be gunned down by the police in the 2000s, and Diggy Dap is rumored to have fled the country over a decade ago after witnessing the murder of one of his close associates, another Crip leader named George Junie Balls McKenzie, in 2007.

Back then in the 90s these guys didn't hurt innocent people. They only hurt who they had a problem with, said Pipe. Nowadays, the guys hurt anybody. They hurt brothers, sisters, mothers, and fathers. Anyone who they could catch, they hurt. Like this crew that is there right now, has no sense, no discipline. Theyre ruthless.

Pipe spoke with VICE World News just days after the May 7 murder of Gerald Tillett Jr. and the prison walls were buzzing with the recent arrival of 18-year-old Kalief Caceres, who police alleged had been the trigger man in the slaying. It was well known that the two teenagers had beef. They'd both been held together in the youth ward of the prison in March 2020 and grew up blocks from each other.

Clinton Harris, 33, a former Blood in prison for a 2012 murder, knew Tillett Jr. and Caceres well; he'd worked as a youth mentor in the prison's under 18 facility when the two were behind bars the year prior.

All they did was fight and quarrel, said Harris.

In the 2000s, the Tillett family became prominent players in the George Street Gang, led by Sheldon Pinky Tillett, and his brother, Gerald Shiny Tillett Sr. The George Street Gang had become bitter enemies with a rival Blood clique a few blocks away called the Taylors Alley Gang. That feud hit overdrive in 2012 when the leader of the Taylors Alley Gang, Arthur Young, allegedly gunned down Pinky Tillett at a gas station in a murder that went viral in Belize and is still visible on Youtube. Pinky Tilletts death led to a series of retaliatory killings and a week later Arthur Young died at the hands of police. Tilletts murder still loomed large over the Southside.

Harris explained that while Caceres wasnt a member of Arthur Youngs family, the elder Blood had been close with Caceres and brought him into the gang from an early age, so in a way, while not connected by blood, they were Bloods.

It was a shadow over those guys, recalled Harris about Tillett Jr. and Caceres. They believed that they had to continue that conflict.

After the death of Pinky Tillett, his brother, Gerald Shiny Tillett Sr. led the gang for several years before being gunned down himself in 2016. Tillett Jr. was only 12 years old at the time of his fathers murder, but by then, he thought that the George Street Gang was his duty in life, explained Harris.

Tillett Jr. had no intention of trying to leave the gang because he believed that was his place because of his dad.

In the days and weeks after Tillett Jrs murder, several alleged gang affiliates were murdered around the Southside, along with numerous other non-fatal shootings. But the still-unsolved murders of Raymond Garcia and Wayne Peteau in the domino den shocked the city as citizens became more concerned that the tentacles of gang violence could reach anyone in the wrong place at the wrong time.

Belize saw a change of the guard in November 2020 when Johnny Briceo became Prime Minister and his People's United Party (PUP) won a majority government, unseating the United Democratic Party (UDP) which, had held power for the previous 12 years.

Briceo entered office facing a long laundry list of challenges, the most immediate being an economy that relies heavily on tourism for roughly 40 percent of its GDP and was decimated by the coronavirus pandemic. His government quickly instituted pay cuts across the government, authorities, and civil society, leading to large protests especially by the teachers union.

Gang violence had fallen into the background of the national discussion as a strict pandemic curfew led to a decrease in violence, but the recent uptick in violent incidents immediately vaulted the country's gang problem back into the forefront half a year after the PUP took office. May would end with 21 murders in Belize, tying with April 2021 and March 2018 as the highest monthly death tolls since 2009.

The issue of gang violence is not something that just happened. It is something that has been coming up over the years. And it's unfortunate that the previous government did not have a well thought out plan on how to deal with it, Prime Minister Johnny Briceo told VICE World News less than a week after the spate of killings. And we're seeing the results, the crime is getting more outrageous, more brazen, more in your face.

He said the killing of innocent people as retaliation in gang violence was something that has rarely happened in Belize. And we are all outraged about it.

During the 12 year reign of the UDP, the former prime minister Dean Barrow instituted a two fold policy to stem gang violence. The UDP infamously negotiated several truces between the gangs, even going so far as to create a work program that paid stipends to those who agreed to stop warring in 2011. While it did lead to a drop in homicides, the program eventually ran out of money the following year and gang violence spiked again.

Barrow also took a firm hand policy against the gangs, most notoriously with the creation of a special police force in 2010 known as the Gang Suppression Unit (GSU). Over the years, a handful of prominent gangsters died at the hands of the cops, although firm accusations of extrajudicial murders by the GSU were never proven.

Several incidents gave the unit a murky reputation.

Arthur Young, the Taylor's Alley Gang boss who died in police custody in 2012, gave numerous interviews over the years claiming that the police wanted to kill him and he even threatened GSU family members on the local news a month before his death. The following year, the corpses of four high-ranking members of the George Street Gang were discovered with their throats slit in an apartment in the Southside. Many have long suspected the GSU committed the killings.

Barrow met with family members of the slain George Street Gang members in the weeks following but claimed there were no truce negotiations. However, by 2014, the police had publicly negotiated another ceasefire. It quickly failed a few months later when old disputes led to seven murders in a 10 day period.

Briceo called the negotiations the biggest mistake of the UDP's time in power because it gave the gangs legitimacy.

Since taking office, Briceo maintains that he wont negotiate with the gangs and promptly followed through on a campaign process to disband the GSU. Although the division did disappear, a new unit quickly took its place called the GI3, which stands for the Gang Intelligence, Investigation and Interdiction Unit. The PUP government claims the new unit will focus more on intelligence gathering rather than hard-handed tactics, but many critics believe its more of the same, old strategy.

Briceo said that his government is trying to change the mindset of the police and to get the respect and support from the community, and you don't get that by beating people.

Over two evenings of ride alongs with the Belize City Quick Response Team, a tactical unit that patrols the city, the police repeatedly pulled over cars and stopped young men on bikes, patting them down looking for drugs and guns, and even broke up a child's birthday party as the family screamed profanities at the officers. The prime minister believed that the strong presence in the Southside was necessary as a way to deter retaliation after Tillett Jr.'s death triggered four murders in five days.

After the flare-up in violence the now opposition UDP quickly put out a statement urging the PUP government to institute a state of emergency in the Southside, which would allow for massive sweeps of known gang members that will take them off the streets for several months without charges. Last year, during his final year in power Dean Barrow instituted two different states of emergencies in the Southside in an attempt to curb the rise in gang violence. Known gang members were arbitrarily detained and held at the Belize Central Prison for several months which, along with coronavirus curfews, led to a significant drop in homicides once again. But the results were not long-lasting. If anything, it led to the recent spate of killings.

Two people picked up in one of those sweeps were Gerald Tillett Jr., and Kalief Caceres, who were housed together in the youth ward for a month where their disagreements intensified.

The PUP remains hesitant about taking such drastic measures, which they see as ineffective and an overreach of power.

We have to be very careful on how we infringe on the rights of our citizens, and its not something that we just do flippantly, we have to think very carefully before we go down that road, said Briceo. We just have to continue to monitor those areas, those hotspots, and it can be done by a police presence. And I think wed rather do that before we start calling a state of emergency in certain areas of the city.

Instead, Briceos government hoped to institute a number of programs to address gang violence, like creating a cadet corps for youths to instill exercise and discipline, provide free education, apprenticeships and job training. These new initiatives have been delayed by financial constraints related to coronavirus.

We believe that these young kids would now have something to do as opposed to being out in the streets and have nothing to do, and the older guys prey on them, and tell them Hey you want to make a quick buck? Go on and commit a crime, said Briceo. But the only way we can deter that is by getting the economy going again, growing the economy, creating jobs.

Another avenue that the government is seriously considering is legalizing marijuana, which is a primary source of income for many of the gangs.

It's something whose time has come. But we just have to be very careful as to how were going to do it," he said. Ensuring that we have the necessary laws in place as to where we are able to grow, how are you going to cultivate it, and of course, to ensure that the government gets its fair share of taxes, and then how it's going to be sold.

On a dusty side street in a corner of the Southside, a Crip set hangs around, drinking beer, smoking weed, and keeping an eye out for intruders.

This is a dead end, this is we hole, this is we block, nobody who ain't from around here come through here, explained one member who heads the marijuana distribution for the clique.

We supply all this, waving his hands around to show that he sells to the whole neighborhood. The dealer talked about how much of the violence is related to the weed, the beef, and the colors.

But he didn't think legalization would calm things, once it went legal, boy, there'll be more war, be a lot of war.

He suggested that everyone would have weed, but also people would move into other crimes. His arguments didn't make much sense, besides explaining that the weed is a part of everything because without the weed I think, we can't eat.

That's how I live, I don't gotta job. This is what I do for a living. I got my people and I try to take care of them, said the dealer. Me, I'm the breadwinner for my peoples.

These gangsters aren't rich, they don't move kilos of cocaine or run large-scale extortion rackets. It's mostly nickel and dime street-level marijuana dealing that puts food on their plates. At one point, they even start asking for money for booze.

The dealer recalled the job program that Dean Barrow instituted in 2013 as one of the few times when the violence really dipped because they had opportunities, but when that ended, the killings continued.

Another member of the Crip set who works as an enforcer felt he had no other option than to join the gang because of where he was from.

I was born around blue. If I was born around red, I'd be red, said the clique's enforcer.

Killing became a part of life early; he had to murder someone to join the Crips and to prove you're strong enough. Now, he spends most days on his block, helping move weed, and protecting his circle.

I sell weed, you know. We just drink, smoke, enjoy ourselves, you know and anyone wanna fuck with us, we got the tools, we got the heat, we gonna do what we gotta do, said the enforcer. So if you violate me, I bout to kill you like point-blank right. I could meet you at the shop, home, in your yard, anywhere.

As he speaks, a car comes peeling into the alley. A third man who claims that he's one of the bosses of the clique gets out in a huff, speaking in nearly inaudible profanities in a mix of Belizean Creole and English, shouting baow.

The guys said baow, that's what we into, huh? said the enforcer. If you fuck with us you just gonna hear baow, it's easy.

The enforcer careened his head to overhear the conversation breaking out among the other Crips in the yard.

Sounds like somebody wants to bust on us right now. That's what he's saying, said the enforcer. He gets up, ends the interview, finds a gun stashed nearby, and disappears.

The boss explained that he'd been in his car when a rival crew spotted him and unleashed a hail of bullets. He'd been able to escape unharmed, this time.

He'd been shot three times before: My leg, my back and then my arm. But still he didn't think about imminent death often because too much thinking is bad for the brain.

In Belize City, the violence always comes and goes, said the boss, like fruits right, got the mango season. Sometimes its the killing season. It's like a disease, like AIDS, theres no cure.

Ben Solomon, Maeva Bambuck, Zach Caldwell, and Jose A. Sanchez contributed to this report.

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How the US Exported a Bloods and Crips Gang War to Belize - VICE

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