Category Archives: Gene therapy

For Immediate Release: August 17, 2022

Today, the U.S. Food and Drug Administration approved Zynteglo (betibeglogene autotemcel), the first cell-based gene therapy for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell transfusions.

Todays approval is an important advance in the treatment of beta-thalassemia, particularly in individuals who require ongoing red blood cell transfusions, said Peter Marks, M.D., Ph.D., director of the FDAs Center for Biologics Evaluation and Research. Given the potential health complications associated with this serious disease, this action highlights the FDAs continued commitment to supporting development of innovative therapies for patients who have limited treatment options.

Beta-thalassemia is a type of inherited blood disorder that causes a reduction of normal hemoglobin and red blood cells in the blood, through mutations in the beta-globin subunit, leading to insufficient delivery of oxygen in the body. The reduced levels of red blood cells can lead to a number of health issues including dizziness, weakness, fatigue, bone abnormalities and more serious complications. Transfusion-dependent beta-thalassemia, the most severe form of the condition, generally requires life-long red blood cell transfusions as the standard course of treatment. These regular transfusions can be associated with multiple health complications of their own, including problems in the heart, liver and other organs due to an excessive build-up of iron in the body.

Zynteglo is a one-time gene therapy product administered as a single dose. Each dose of Zynteglo is a customized treatment created using the patients own cells (bone marrow stem cells) that are genetically modified to produce functional beta-globin (a hemoglobin component).

The safety and effectiveness of Zynteglo were established in two multicenter clinical studies that included adult and pediatric patients with beta-thalassemia requiring regular transfusions. Effectiveness was established based on achievement of transfusion independence, which is attained when the patient maintains a pre-determined level of hemoglobin without needing any red blood cell transfusions for at least 12 months. Of 41 patients receiving Zynteglo, 89% achieved transfusion independence.

The most common adverse reactions associated with Zynteglo included reduced platelet and other blood cell levels, as well as mucositis, febrile neutropenia, vomiting, pyrexia (fever), alopecia (hair loss), epistaxis (nosebleed), abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder and pruritus (itch).

There is a potential risk of blood cancer associated with this treatment; however, no cases have been seen in studies of Zynteglo. Patients who receive Zynteglo should have their blood monitored for at least 15 years for any evidence of cancer. Patients should also be monitored for hypersensitivity reactions during Zynteglo administration and should be monitored for thrombocytopenia and bleeding.

This application was granted a rare pediatric disease voucher, in addition to receiving Priority Review, Fast Track, Breakthrough Therapy, and Orphan designations.

The FDA granted approval of Zynteglo to bluebird bio, Inc.

###

Boilerplate

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nations food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

08/17/2022

Go here to read the rest:
FDA Approves First Cell-Based Gene Therapy to Treat Adult and Pediatric Patients with Beta-thalassemia Who Require Regular Blood Transfusions -...

WATCH TIME: 3 minutes

For approximately 90% of all cases of amyotrophic lateral sclerosis (ALS), there is no known family history of the disease or presence of a genetic mutation linked to the disease. Although, for the remaining 5% to 10%, there is a known family history of the disease that has opened the door for gene therapy, a targeted approach that can potentially fix or block the negative effects of coding errors. Some of the most promising gene-therapybased approaches for ALS to date include antisense oligonucleotides, RNA interference, or gene editing technology such as CRISPR.

With close to 40 different genes discovered that are linked to the disease, the main issue is now validating the genes. One of these, SARM1, a variant thought to promote neuron death, is also being evaluated by several researchers from Kings College London. The project will use stem cells converted to neurons in a laboratory to firmly establish a causative role for the variant, as well as manipulate the cell culture environment and other genes to identify risk factors interacting with it.

There are several reasons why the research has not translated to therapeutic success, says Anna Underhill, BS, an investigator of the project. Underhill, a postdoctoral researcher at Kings College London, sat down with NeurologyLive to discuss the complexities of gene therapy, where the lag stems from, and the future directions of her study. She also provided detail on the uniqueness of SARM1 mutation, including a possible compensatory mechanism in the cell.

The rest is here:
Overcoming the Complexities With Gene Therapy in ALS: Anna Underhill, BS - Neurology Live

Dublin, Aug. 19, 2022 (GLOBE NEWSWIRE) -- The "Gene Therapy - Global Market Trajectory & Analytics" report has been added to ResearchAndMarkets.com's offering.

Global Gene Therapy Market to Reach $2.7 Billion by 2026

Amid the COVID-19 crisis, the global market for Gene Therapy estimated at US$1.2 Billion in the year 2022, is projected to reach a revised size of US$2.7 Billion by 2026, growing at a CAGR of 19.5% over the analysis period.

Gene therapy is growing at an impressive pace, having emerged as a prospective segment in the field of biotechnology, and also presenting a bright outlook, given the increasing investments in R&D as well as mounting incidence of genetic disorders.

The rapid growth in global population, along with growing incidence of cancer and chronic disorders, introduction of novel gene therapy-based products, strong clinical evidence for therapeutic efficacy and safety of gene therapy products, favorable reimbursement policies and guidelines, and rapidly growing demand for chimeric antigen receptor (CAR) T-cell-based gene therapies are some of the key factors driving growth in the market.

Moreover, rising awareness regarding the potential of gene therapy in treating various chronic diseases, ethical acceptability of gene therapy for treating cancer, and increased government support for promoting research in gene therapy are expected to bolster the market growth in the coming years

Viral, one of the segments analyzed in the report, is projected to record 19.7% CAGR and reach US$3 Billion by the end of the analysis period. After a thorough analysis of the business implications of the pandemic and its induced economic crisis, growth in the Non-Viral segment is readjusted to a revised 17.6% CAGR for the next 7-year period. Viral segment accounts for a major share of the market.

Deployment of viral vectors in delivery of gene therapy drugs continue to exhibit progressive tide, driven by wider availability of advanced mechanisms for quicker and effective modifications of viruses such as Adeno-Associated Virus (AAV), Lentivirus, Retrovirus & Gamma-Retrovirus, Herpes Simplex Virus, Poxvirus, and Vaccinia Virus, among others.

Robust improvement in RNA, DNA, and oncolytic viral vectors is encouraging the prospects of viral vectors. Non-viral vectors are perceived as safer substitute to viral vectors, and playing an important role in redirecting pharmaceutical industries and clinicians towards gene therapy. The demand for non-viral vectors is also attributed to factors like easy characterization, mass production, enhanced reproducibility, superior transgenic capacity, and few bio-security issues.

The U.S. Market is Estimated at $628.1 Million in 2022, While China is Forecast to Reach $82.3 Million by 2026

The Gene Therapy market in the U.S. is estimated at US$628.1 Million in the year 2022. China, the world's second largest economy, is forecast to reach a projected market size of US$82.3 Million by the year 2026 trailing a CAGR of 25.1% over the analysis period. Among the other noteworthy geographic markets are Japan and Canada, each forecast to grow at 17.3% and 18.9% respectively over the analysis period.

Within Europe, Germany is forecast to grow at approximately 18.6% CAGR. The presence of large market players, availability of favorable reimbursement policies, prevalence of advanced healthcare infrastructure, high healthcare spending, the availability of high disposable income among the consumer base, and rising incidence of chronic diseases are some of the key factors that are expected to continue driving growth in the US market.

In Europe, rising funding for cell and gene therapy programs in countries such as the UK is expected to steer the gene therapy market in the region. European companies with commercial gene therapy portfolios are actively seeking roll out of their treatments in other regional markets by winning approvals from concerned regulatory bodies.

Growth in the Asia-Pacific region is attributed to the rising prevalence of cancer, growing government initiatives for improving healthcare infrastructure, and increasing healthcare expenditure by various countries across the region.

What`s New for 2022?

Key Topics Covered:

I. METHODOLOGY

II. EXECUTIVE SUMMARY

1. MARKET OVERVIEW

2. FOCUS ON SELECT PLAYERS(Total 154 Featured):

3. MARKET TRENDS & DRIVERS

4. GLOBAL MARKET PERSPECTIVE

III. REGIONAL MARKET ANALYSIS

IV. COMPETITION

For more information about this report visit https://www.researchandmarkets.com/r/qge6hb

Read the original post:
Global Gene Therapy Market Report 2022: Amid the COVID-19 Crisis, the Market is Projected to Reach a Revised Size of $2.7 Billion by 2026 -...

Breadcrumb Trail Links

The family is cautiously optimistic about the improvements they are seeing in Michael, 4, since the gene therapy three months ago

Publishing date:

Doctors and researchers at The Hospital for Sick Children in Toronto have conducted one of the first individualized gene therapies as part of a single-patient clinical trial.

This advertisement has not loaded yet, but your article continues below.

There is hope that this success will begin to carve a path for precision child health care and more patients will have the opportunity to receive individualized care and treatments for a wide range of conditions.

David Malkin, lead of the Precision Child Health initiative, director of the Cancer Genetics Program, and the CIBC Childrens Foundation Chair in Child Health Research at SickKids, said the idea behind precision medicine is to use the unique features of an individual to make diagnosis more precise and to predict approaches and outcomes to treatments.

The concept is that we take all information, from the postal code to the genetic code, so it is more than medicine, its overall health and everything that encompasses, said Malkin.

This advertisement has not loaded yet, but your article continues below.

This groundbreaking individualized gene therapy procedure was years in the making.

After fundraising over $3.5 million to develop the therapy, successfully testing it in mice, and finally getting Health Canada approval, Toronto-born four-year-old Michael Pirovolakis received the procedure in March to hopefully slow the progression of his ultra-rare genetic condition, SPG50.

In April 2019, Michael was diagnosed with the progressive neurodegenerative disorder spastic paraplegia type 50 or SPG50. This condition, which is caused by variants in a gene called AP4M1, causes developmental delays, speech impairment, seizures, and progressive paralysis of the arms and legs. Over the course of a few years, children lose the ability to walk and use their hands, and eventually lose their mental capacity. It is also likely to be fatal.

This advertisement has not loaded yet, but your article continues below.

Michael is currently the only known patient with the condition in Canada. It is estimated that there are around 80 other children with SPG50 around the world, making it an ultra-rare disease.

Having a child with an ultra-rare disease is difficult, said Terry Pirovolakis, Michaels father. Someone has to be watching him at all times because he doesnt understand that climbing up on the couch or opening the fridge door could be unsafe.

We love him more than anything, you know, but it is difficult, he said.

Upon diagnosis, the treatment options for SPG50 were extremely limited. So, Terry and his wife Georgia started the charity CureSPG50 to raise money to develop a gene therapy that would help their son and others with SPG50.

This advertisement has not loaded yet, but your article continues below.

Gene therapies are usually used to treat conditions caused by genetic mutations, said Jim Dowling, staff physician in the Division of Neurology and senior scientist in the Genetics & Genome Biology program at SickKids.

The idea is that through some delivery mechanism, a gene is added back to an individual, he said.

Currently, the standard way of delivery is to replace the DNA of a virus, most commonly an adeno-associated virus (AAV), with the healthy DNA of the mutated gene. An AAV is used because people do not get sick when they are exposed to it, said Dowling.

This advertisement has not loaded yet, but your article continues below.

The virus is then given to the patient in a way that is specific to their condition. Sometimes this is through an IV, sometimes into the muscle, or even into the eyeball. For SPG50, gene therapy is given into the spinal fluid so it can easily access the brain.

There are risks associated with the gene therapy procedure, specifically if the patient may develop cancer.

It was exciting that we can give Michael a better life, but scary at the same time because the last thing I ever want to do is hurt my child, said Terry

What was especially unique about Michaels gene therapy was that it was designed specifically for him and his condition, said Dowling, who led Michaels clinical trial.

This type of individualized treatment is what the doctors behind the Precision Child Health initiative at SickKids have been working towards.

This advertisement has not loaded yet, but your article continues below.

Currently, the precision child health team is gathering case studies that show the use of individualized medicine, like Michaels gene therapy, to create a plan on how to go from the discovery of disease to medical intervention.

They hope that they will soon be able to give the same specialized treatment that Michael received to many more children with many different types of conditions.

Terry said that he and his family are cautiously optimistic about the improvements they are seeing in Michael since the gene therapy three months ago. He is doing well and there are small signs that his symptoms may be improving.

We wouldnt have gotten here without the amazing people helping us along the way, said Terry. I want to thank everybody for just truly being there for us.

This advertisement has not loaded yet, but your article continues below.

Michael will hopefully not be the only child that receives gene therapy to treat SPG50.

Currently, another batch of treatment is being made with the hope of having 10 doses to give to other kids, said Terry. If all goes to plan and the U.S. Food and Drug Administration (FDA) approves the treatment, in October there will be another clinical trial in Texas.

Terry said this plan relies on CureSPG50 raising another quarter of a million dollars per child. The money is needed to cover a five-year study and hospital costs.

Our goal is to save as many kids as we humanly can, said Terry. I hope we can raise enough money to eradicate this disease.

This advertisement has not loaded yet, but your article continues below.

This advertisement has not loaded yet, but your article continues below.

Sign up to receive the daily top stories from the National Post, a division of Postmedia Network Inc.

A welcome email is on its way. If you don't see it, please check your junk folder.

The next issue of NP Posted will soon be in your inbox.

We encountered an issue signing you up. Please try again

Postmedia is committed to maintaining a lively but civil forum for discussion and encourage all readers to share their views on our articles. Comments may take up to an hour for moderation before appearing on the site. We ask you to keep your comments relevant and respectful. We have enabled email notificationsyou will now receive an email if you receive a reply to your comment, there is an update to a comment thread you follow or if a user you follow comments. Visit our Community Guidelines for more information and details on how to adjust your email settings.

Read more:
Canadian family raised $3.5M to develop individualized gene therapy for son's rare condition - National Post

Prescient has joined forces with Thermo Fisher Scientific for a research program aiming to advance development of its next-generation cellular therapies.

Clinical stage oncology companyPrescient Therapeutics (ASX:PTX) has signed an agreement with Thermo Fisher Scientific to accelerate development and commercialisation of a highly scalable version of its game-changing OmniCAR cell therapy platform.

Thermo Fisher is a world leader in cell and gene technologies. The agreements development plan will evaluate the potential of using automated, closed cell therapy solutions to develop a novel process of manufacturing cell therapies on Prescients OmniCAR platform using non-viral methods.

Prescient is working to develop personalised therapies to treat cancer, with the deal leveraging Thermo Fishers expertise in cell and gene therapy to create a scalable cell therapy platform. The work program aims to develop the next generation OmniCAR cells that can be produced with greater efficiency, lower costs and unmatched reproducibility.

Its been a week of positive news for Prescient, which also announced it had entered a manufacturing servicesdeal with specialist cell therapy manufacturer, Q-Gen Cell Therapeutics (Q-Gen), to produce itsOmniCAR cell lines for upcoming clinical trials.

All CAR-T therapies approved by the US Food and Drug Administration (FDA) so far, and most CAR-T therapies in development, employ viral vectors to insert genetic material into immune cells to create chimeric antigen receptors (CARs)-expressing immune cells.

Viral vectors are expensive, relatively inefficient, and time consuming to develop, often representing a key bottleneck and major cost contributor to CAR-T manufacturing.

Viral transduction processes are highly complex manual processes which are challenging for tech transfer, labour intensive and prone to operator variations, therefore producing highly variable and unpredictable results.

The work plan under this agreement will focus on creating OmniCAR cells with Thermo Fishers portfolio of proprietary equipment and specialised cell and gene therapy manufacturing expertise.

A key Prescient objective is to create a second generation of the OmniCAR platform by being able to manufacture OmniCAR cells with greater efficiency and lower costs that are suitable for tech transfer to GMP-licensed contract development and manufacturing organisations globally.

This in turn feeds into Prescients vision of decentralised manufacturing, which is best suited for multi-centre treatments, both during development and eventually for commercial roll-out.

The substantial research is forecast to take around 12 months to complete, with Prescient receiving full ownership of outcomes from the collaboration. Prescient is not required to make any cash contribution to the project.

Prescient believes that the agreement provides an opportunity for future development of other gene edits for incorporation into further-enhanced OmniCAR cell therapies to address exhaustion and immune suppression.

Prescient Managing Director and CEO Steven Yatomi-Clarke said the company elected to develop its first internal OmniCAR programs using the validated approach of lentiviral transduction.

However, he said it had always had an eye on the future for any emerging advantages that can be incorporated into its programs whilst mitigating development risk.

We are optimistic that this agreement with Thermo Fisher will accelerate the development of the OmniCAR platform to the point where one or more of Prescients internal OmniCAR programs can incorporate the advancements this agreement produces, he said.

Importantly, the agreement should result in an improved product and process that can be decentralised and therefore scaled with high efficiency and reproducibility.

Such innovation is crucial in the clinical and eventual commercial rollout of OmniCAR products and will facilitate third-party development of OmniCAR and the companys ultimate vision of a patient-centric treatment ecosystem.

Join Prescient Therapeutics Managing Director and CEO Steven Yatomi-Clarke for an investor briefing on Tuesday 23rd August at 12pm (AEST). Register for the session here.

This article was developed in collaboration with Prescient Therapeutics, a Stockhead advertiser at the time of publishing.

This article does not constitute financial product advice. You should consider obtaining independent advice before making any financial decisions.

Get the latest Stockhead news delivered free to your inbox.

"*" indicates required fields

It's free. Unsubscribe whenever you want.

You might be interested in

Original post:
Prescient joins world-leader in cell and gene therapy to accelerate OmniCAR platform - Stockhead

New DME treatments aim to extend time between intravitreal injections.

Therapies that block VEGF have become the mainstay of interventional treatment for retinal vascular disorders including neovascular age-related macular degeneration (nvAMD), diabetic macular edema (DME), and retinal venous occlusive disease.1

Over the past few years, intravitreal anti-VEGF therapy (AVT) has been shown to be very effective for patients with diabetic retinopathy (DR), reducing its severity and subsequent vision-threatening complications such as proliferative diabetic retinopathy (PDR) and anterior segment neovascularization in patients with nonproliferative DR,2 as well as center-involved diabetic macular edema (CI-DME).3

In January, the FDA approved faricimab (Vabysmo, Genentech) to treat DME and nvAMD.4 It joins ranibizumab (Lucentis, Genentech) and aflibercept (Eylea, Regeneron) for this indication, although it is not yet approved for treating DR in isolation.

Faricimab is a bispecific monoclonal antibody targeted against both VEGF-A and angiopoietin-2 receptors. In the RHINE (NCT03622593) and YOSEMITE (NCT03622580) trials, faricimab demonstrated noninferiority compared with aflibercept against CI-DME in terms of vision gained and reduction in central retinal thickness.

Trial participants randomly assigned to take faricimab gained 1 ETDRS letter and 20 to 30 m additional reduction in optical coherence tomography (OCT), central subfield thickness (CST) at 1 year, and these gains were sustained at 2 years.4

Moreover, 70% of participants taking faricimab were able to extend the time between injections to 12 or more weeks (50% were able to extend to 16 weeks), compared with 30% of participants taking aflibercept, thus reducing the burden of treatment.

In year 2, 80% of eyes were able to extend treatment intervals to 12 or more weeks with faricimab.5 No new safety signals were seen in roughly 900 participants in each arm, but it is worth noting that 5 eyes in the faricimab group versus 1 eye in the aflibercept group experienced a retinal artery occlusion, vein occlusion, or other retinal embolic eventthough none of these were associated with inflammation/vasculitis.

Brolucizumab (Beovu, Novartis) is another AVT monoclonal antibody previously approved for nvAMD. Unfortunately, postapproval analysis showed a small but definite increased risk of intraocular inflammation (IOI) and/or retinal vascular occlusion (RO), with an overall incidence of 2.4%. Risk was substantially higher in patients who had IOI/RO within 12 months of drug initiation.6

Novartis is currently seeking approval for brolucizumab in patients with DME based on results from the KESTREL (NCT03481634) and KITE (NCT03481660) studies showing noninferiority compared with aflibercept.

More than 50% of participants achieved every 12-week dosing. Further, the incidence of IOI/RO was lower than what was seen in patients with nvAMD, but was still higher than those with aflibercept (4.1% for brolucizumab versus 1% aflibercept).7

One goal of these newer therapies is extending the time between intravitreal injections required to maintain both absence of disease activity and vision gains, given the relatively short half-life of current AVT. Gene therapy introduces genetic material into patients cells to compensate for faulty genes or deliver therapeutic transgenes capable of producing therapeutic molecules.8

In diabetic retinal disease, adenovirus-associated vectors (AAVs) modified to produce anti-VEGF and other antiangiogenic or neurovascular-protective molecules are implanted within the vitreous, sub-retinal pigment epithelium (RPE), or suprachoroidal space.

Animal trials have shown success, and results from a 1 phase II human trial showed improvement in DR severity sans DME at 6 months,9 whereas another trial in participants with CI-DME was terminated early due to safety concerns that included hypotony, inflammation, and vision loss.10 Retina specialists are optimistic that AAVs hold great promise for both DR/DME and AMD.

Another pathway distinct from VEGF, but directly implicated in the pathogenesis of DME, is plasma kallikrein (PKal), a protein synthesized in the liver that mediates vascular leakage and inflammation, levels of which are elevated in the vitreous of patients with diabetic retinopathy.11

Results from KALAHARI (NCT04527107), a phase II study of PKal inhibitor THR-149 (Oxurion), showed 6.1 letters of visual acuity improvement and CST reduction of 100 m after 3 monthly injections in participants with DME suboptimally responsive to a minimum of 5 prior anti-VEGF injections (baseline BCVA ranging from 20/40 to 20/160, with baseline CST averaging 421 m). At 6 months, 50% of participants had a 2-line improvement in BCVA with no additional rescue therapy.

The study was small20 total participantsand only the highest dose affected acuity gains, but these findings offer additional hope of improved vision for patients who dont respond adequately to AVT.12

Integrins are transmembrane receptors that allow cell-to-cell and cell-to-extracellular matrix adhesion and biochemical signal transduction. They have been implicated in DR and DME by activating growth factor receptors both upstream and downstream from VEGF.13

The integrin antagonist THR-687 (Oxurion) was assessed in a phase 1 trial (NCT03666923) at 3 doses in 12 participants with DME previously treated with AVT, mean visual acuity of 20/80 and mean CST of 542 m.

Mean improvement of 7.2 letters was seen at 1 week and 9.2 letters at 1 month, as well as a 106-m decrease in CST at 2 weeks that waned to a 37-m reduction by month 3.

A phase 2 trial (NCT05063734) of THR-687 in treatment-nave participants with DME is due for completion in August 2023. Several other anti-integrin therapies are in clinical trials, including at least 1 self-administered eye drop that reaches the posterior segment.14,15

Another possible treatment for DME is photobiomodulation (PBM), an LED or LASER application of visible light (typically 670 nm) that activates cytochrome-C oxidase within retinal mitochondria, enhancing cellular metabolism (ATP production) and reducing reactive oxygen species that play a critical role in diabetic eye disease.

Results of a study of patients with CI-DME, CST greater than 300 m, and best-corrected vision ranging from 20/30 to 20/200 showed a significant 59-m reduction at 2 months (p = 0.03), though acuity results were not reported.16

Investigators in a recent clinical trial from the DRCR Retina Network (Protocol AE) compared placebolow energy, broad spectrum white lightwith PBM for 90 seconds, twice daily for 4 months in 135 participants with center-involved DME and good vision (> 20/25).15 Unfortunately, both mean CST and vision in the treated group worsened only 2 m/0.4 letters less in the PBM group versus placebo (both insignificant).17 This suggests PBM may be most effective for those with more substantial DME.

Of note, top-line data from the LightSite III trial (NCT04065490) showed that using PBM at 3 wavelengthsyellow, red, and near infraredfor intermediate dry AMD yielded a 5.5-letter improvement in the treatment (n = 91 eyes) versus sham treatment (n = 54 eyes) arms at 13 months.18 The investigation of PBM for both AMD and DME continues.

There now are multiple therapies for treating both DME and DR, with more on the horizon. This is particularly good news for those patients who dont respond well to traditional therapies and may reduce the treatment and vision burden of these all-too-common disorders.

Visit link:
It's not your grandparents' anti-VEGF therapy - Optometry Times

Alzheimer's has been reversed in mice after scientists boosted the formation of new brain cells. A gene therapy fuelled neurons in the hippocampus - a region vital for learning and remembering.

The breakthrough could lead to new treatments. The number of dementia cases worldwide will triple to 150 million by 2050. There is no cure. Lead author Professor Orly Lazarov, of the University of Illinois, Chicago, said: "Taken together, our results suggest augmenting neurogenesis may be of therapeutic value."

Experiments have shown the process is impaired in patients and mice with mutations linked to Alzheimer's - particularly in the hippocampus. The US team found increasing production of neurons rescued the lab rodent's defects.

They were incorporated into memory circuits - restoring normal function. The study offers hope of a viable strategy. Current drugs target just the symptoms - and not the cause.

Brain cells send electric signals. We keep making them throughout our lives. They are produced by neural stem cells. But numbers tail off as we age - and fall dramatically in Alzheimer's. Evidence is improving neurogenesis holds the key to curing dementia.

The hippocampus is the region of grey matter you need, for instance, to remember where you parked your car. Prof Lazarov said: "However, the role of newly formed neurons in memory formation, and whether defects in neurogenesis contribute to the cognitive impairments associated with Alzheimer's, is unclear."

In the study, stem cell survival was enhanced by deleting a gene called Bax - leading to the maturation of more neurons. Afterwards, the animals regained the animals' regained their spatial recognition and contextual memory skills. tests included finding their way around a maze.

Scans of healthy mice showed the circuits involved in storing memories include many newly formed neurons alongside older ones. Neurons were fluorescently labelled - lighting up as they were activated during acquisition and retrieval.

The memory-stowing loops of mice with Alzheimer's contained fewer. But integration of newly formed brain cells was restored when neurogenesis was increased. Further analyses revealed there was also a rise in the number of tiny protrusions called dendritic spines. They connect neurons - and are critical for memory formation.

When the researchers specifically inactivated the new neurons, mice with dementia lost any improvement in memory - confirming the results. Prof Lazarov added: "Our study is the first to show impairments in hippocampal neurogenesis play a role in the memory deficits associated with Alzheimer's by decreasing the availability of immature neurons for memory formation."

Alzheimer's and other forms of dementia affect more than 920,000 people in the UK - a figure that will reach teo million within three decades. The study was published in the Journal of Experimental Medicine (JEM).

Read more from the original source:
Alzheimer's breakthrough: Scientists reverse disease with gene therapy - Nottinghamshire Live

Only one in eight HIV cure studies are being conducted in sub-Saharan Africa, but a few important studies have got off the ground in recent years. In South Africa, young women with very recent infection are testing broadly neutralising antibodies and vesatolimod, while gene therapy research is underway in Uganda. In the prevention field, early work on an mRNA vaccine is being done in Rwanda and South Africa.

The studies were discussed at a pre-conference meeting on cure held before the 24th International AIDS Conference (AIDS 2022), as well as at the conference itself.

Curing complex conditions like cancer and inherited diseases can involve equally complex, expensive drugs. This is especially problematic with HIV, an infectious disease targeting, in general, the poorest and most disadvantaged people in the world. Sub-Saharan Africa accounts for almost 70% of the global HIV burden and 59% of new global infections in 2021.

To eliminate a disease or a condition in an individual, or to fully restore health. A cure for HIV infection is one of the ultimate long-term goals of research today. It refers to a strategy or strategies that would eliminate HIV from a persons body, or permanently control the virus and render it unable to cause disease. A sterilising cure would completely eliminate the virus. A functional cure would suppress HIV viral load, keeping it below the level of detection without the use of ART. The virus would not be eliminated from the body but would be effectively controlled and prevented from causing any illness.

A type of experimental treatment in which foreign genetic material (DNA or RNA) is inserted into a person's cells to prevent or fight disease.

A neutralising antibody (NAb) is an antibody that fully defends its target cell from an antigen. A broadly neutralising antibody (bNAb) is a neutralising antibody that has this effect against a wide range of antigens. A number of broadly neutralising antibodies have been isolated from persons living with HIV. Some of them are being studied and, in some cases, used in clinical trials, to defend humans against HIV infection, treat HIV infection, and kill HIV-infected CD4+ T cells in latent reservoirs.

A unit of heredity, that determines a specific feature of the shape of a living organism. This genetic element is a sequence of DNA (or RNA, for viruses), located in a very specific place (locus) of a chromosome.

Dr Elizabeth Barr of the US National Institutes of Health told the pre-conference meeting that they had counted 162 HIV cure studies in 2019. Of these, three-quarters were being conducted in North America (76, almost all in the US) or in Europe (44, with France leading the way at 12). There were 23 in Asia and Oceania and eight in Latin America and the Caribbean, and only 19 (12%) in sub-Saharan Africa.

In addition, crucial groups, most notably women, were under-represented. Only one in six cure study participants were cisgender women and 1.4% were transgender people (mainly women), even though women respond to HIV differently from men. People over 50 only formed 7%. The survey did not cover babies and children taking part in studies.

But how to involve people in the global South in cure research now? We need to do this not only to ensure universal applicability if one is developed and to ensure fair inclusion, but also to counter myths and misunderstandings (for instance, that a particular therapy is a cure rather than a single step on a long road).

Perhaps the best example of paying attention to the needs and expectations of participants in cure research in lower-income settings is provided by the FRESH cohort in KwaZulu-Natal, South Africa (the FRESH acronym stands for Females Rising through Education, Support, and Health). Based on a similar cohort in Thailand, it recruits young women aged 18-23 in one of the highest-incidence areas for HIV in the world.

It tests its participants for HIV very frequently twice a week. The object is to treat them in the very earliest detectable states of HIV infection (Fiebig 1 and 2, before antibodies appear) to find out if this limits the progression of HIV later, and what the immunological signature of the young women is, to see if it can be reverse-engineered into a vaccine or cure for others.

Dr Krista Dong of FRESH told the meeting that so far it has recruited 2916 young women of whom 90 have tested HIV positive. The median number of days, it is estimated, between infection and the first positive test is only four an extraordinary achievement in itself. All 90 are on antiretroviral therapy (ART).

Of these, 29 have so far consented to leukapheresis, the process of extracting lymphocytes so their immune function can be tested.

But FRESH is a lot more than just a test-early-and-treat project. It also offers an empowerment and life-skills curriculum for its participants with computer training, literacy and numeracy classes, and workshops. The women are tested for HIV twice a week over a nine-month period when they come to attend the empowerment classes.

It is partly the mark of the painstaking consideration that went into FRESH that clinical trials of potential prevention and cure therapies only started in 2021 even though the cohort started recruiting in 2012. (It is also due to a year under COVID lockdown during which tests were suspended, floods cut the road to the research clinic, and political unrest led to the wrecking of the clinic which re-established itself the next day in the car park of a local hospital.)

The first study was a prevention one, of using a Lactobacillus supplement to treat bacterial vaginosis and see if it helped prevent infection.

But the second study is a phase 2a acceptability and tolerability cure study: in partnership with Gilead Sciences, 25 participants are being given two broadly neutralising antibodies, VRC07-523 and CAP256V, in combination with Gileads TLR-7 agonist, vesatolimod. ART will be stopped for up to 43 weeks (or longer if viral suppression is maintained). The first participant received her first ART plus antibody infusions on 13 July this year.

Innovative HIV vaccine studies are also underway in sub-Saharan Africa. Dr Kundai Chinyenze of the International AIDS Vaccine Initiative (IAVI) told AIDS 2020 that phase I clinical trials to evaluate the safety and immune response of an mRNA HIV vaccine antigen (mRNA-1644) have started in Rwanda and South Africa.

Led by a team of African scientists, IAVI G003 has enrolled 18 healthy HIV-negative adult volunteers to test whether vaccine injection with eOD-GT8 60mer, delivered via Modernas mRNA platform, can induce similar immune responses in African populations as were seen in IAVI G001.

Results from IAVI G001 (in US adults) demonstrated that vaccination with the HIV immunogen eOD-GT8 60mer safely targeted nave B cells with specific properties in 97% of recipients. This process is known as germline targeting. Once stimulated, this specific class of B cells can generate broadly neutralising antibodies (bnAbs). The induction of bnAbs is widely considered a goal of an efficacious HIV vaccine, and this B-cell activation is the first step in that process.

All participants of the IAVI G003 will receive two doses of eOD-GT8 60mer mRNA, and their immune responses will be examined to evaluate whether the targeted responses have been achieved. Novel sampling techniques being used in this trial include ultrasound-guided fine needle aspiration, where two weeks after each immunisation, a thin needle will be used to access the lymph nodes of participants to monitor in real-time B-cell responses in germinal centres. Another technique is leukapheresis, where eight weeks after the second dose, white blood cells will be extracted from participants to allow deep characterisation of the B-cell responses.

From Uganda, Dr Cissy Kityo told the conference that the Joint Clinical Research Centre in Kampala has teamed up with Fred Hutchinson Center in Seattle to develop a gene therapy treatment for HIV that will be ready for testing in Uganda by 2024. This will be the first gene therapy trial in Africa. The licensed product which will be evaluated in Uganda is the Anti-HIV duoCAR-T cell therapy; it modifies T cells such that they may be able to directly control HIV in the absence of therapy. This product is currently being evaluated in Phase 1 clinical trials at the University of California, San Francisco.

Uganda is also currently developing genetic engineering policy and the regulatory approval pathway. One Ugandan scientist is currently being trained to manufacture gene therapy products at the Fred Hutchinson Center.

But what do people living in Africa want from an HIV cure? What will it need to cost? What can be practically given in non-urban clinics? Are interventions like gene therapy acceptable? These are the questions Professor Sharon Lewin, the new president of the International AIDS Society, wants researchers to consider when undertaking HIV cure trials in Africa.

She also pointed out that scientific issues like HIV subtype, genetics unique to the dominant African population, and common prevalent co-morbidities must be considered by HIV cure research scientists in Africa.

While strengthening HIV cure research in Africa is a top priority because of the high burden and distinct characteristics of HIV in the region, a cure which is scalable, affordable and available will only be achieved if researchers engage and work with affected communities, local scientists, and local HIV care advocates.

More:
A cure must be a cure for all: why more HIV cure research in Africa is needed - aidsmap

Taysha Gene Therapies (NASDAQ:TSHA Get Rating) had its price target cut by Chardan Capital from $34.00 to $32.00 in a research note published on Friday, Marketbeat reports. They currently have a buy rating on the stock.

TSHA has been the subject of a number of other reports. Wedbush reduced their price target on shares of Taysha Gene Therapies from $9.00 to $5.00 and set an outperform rating for the company in a report on Friday. The Goldman Sachs Group lowered their price objective on shares of Taysha Gene Therapies from $27.00 to $16.00 and set a buy rating on the stock in a research report on Tuesday, May 24th. Guggenheim reduced their target price on shares of Taysha Gene Therapies to $22.00 and set a na rating for the company in a research note on Tuesday, May 17th. Finally, Needham & Company LLC reduced their price objective on shares of Taysha Gene Therapies to $20.00 and set a buy rating for the company in a research note on Tuesday, May 17th. Twelve investment analysts have rated the stock with a buy rating, According to MarketBeat.com, the stock has a consensus rating of Buy and an average target price of $27.08.

Shares of NASDAQ:TSHA opened at $4.10 on Friday. The companys 50 day moving average price is $3.95 and its two-hundred day moving average price is $4.90. Taysha Gene Therapies has a 12-month low of $2.33 and a 12-month high of $21.90. The firm has a market cap of $166.24 million, a PE ratio of -0.85 and a beta of 0.99. The company has a quick ratio of 2.20, a current ratio of 2.20 and a debt-to-equity ratio of 0.74.

In other Taysha Gene Therapies news, CMO Suyash Prasad sold 23,923 shares of Taysha Gene Therapies stock in a transaction dated Friday, July 1st. The stock was sold at an average price of $3.53, for a total value of $84,448.19. Following the transaction, the chief marketing officer now owns 543,450 shares in the company, valued at $1,918,378.50. The transaction was disclosed in a legal filing with the Securities & Exchange Commission, which is available through the SEC website. Insiders sold 40,152 shares of company stock worth $145,109 over the last three months. 42.40% of the stock is owned by corporate insiders.

Large investors have recently bought and sold shares of the stock. 683 Capital Management LLC acquired a new position in shares of Taysha Gene Therapies during the 4th quarter worth approximately $117,000. ProShare Advisors LLC acquired a new position in Taysha Gene Therapies during the 4th quarter worth about $121,000. Sargent Investment Group LLC acquired a new stake in Taysha Gene Therapies in the 1st quarter valued at about $69,000. Virtus ETF Advisers LLC raised its position in Taysha Gene Therapies by 39.3% in the 4th quarter. Virtus ETF Advisers LLC now owns 11,519 shares of the companys stock valued at $134,000 after purchasing an additional 3,251 shares in the last quarter. Finally, Nisa Investment Advisors LLC acquired a new stake in Taysha Gene Therapies in the 1st quarter valued at about $129,000. 46.05% of the stock is owned by institutional investors and hedge funds.

(Get Rating)

Taysha Gene Therapies, Inc, a gene therapy company, focuses on developing and commercializing adeno-associated virus-based gene therapies for the treatment of monogenic diseases of the central nervous system. It primarily develops TSHA-120 for the treatment of giant axonal neuropathy; TSHA-102 for the treatment of Rett syndrome; TSHA-121 for the treatment of CLN1 disease; TSHA-118 for the treatment of CLN1 disease; TSHA-105 foe the treatment of for SLC13A5 Deficiency; and TSHA-101 for the treatment of GM2 gangliosidosis.

Receive News & Ratings for Taysha Gene Therapies Daily - Enter your email address below to receive a concise daily summary of the latest news and analysts' ratings for Taysha Gene Therapies and related companies with MarketBeat.com's FREE daily email newsletter.

Read more:
Taysha Gene Therapies (NASDAQ:TSHA) PT Lowered to $32.00 at Chardan Capital - Defense World

August 8, 2022

Delivering the protein EPS8 via gene therapy rescues malfunctioning inner ear hair cells that transduce sound

LA JOLLAScientists from the Salk Institute and the University of Sheffield co-led a study that shows promise for the development of gene therapies to repair hearing loss. In developed countries, roughly 80 percent of deafness cases that occur before a child learns to speak are due to genetic factors. One of these genetic components leads to the absence of the protein EPS8, which coincides with improper development of sensory hair cells in the inner ear. These cells normally have long hair-like structures, called stereocilia, that transduce sound into electrical signals that can be perceived by the brain. In the absence of EPS8, the stereocilia are too short to function, leading to deafness.

The teams findings, published in Molecular Therapy Methods & Clinical Development online on July 31, 2022, show that delivery of normal EPS8 can rescue stereocilia elongation and the function of auditory hair cells in the ears of mice affected by the loss of EPS8.

Our discovery shows that hair cell function can be restored in certain cells, says co-senior author Uri Manor, assistant research professor and director of the Waitt Advanced Biophotonics Core at Salk. I was born with severe to profound hearing loss and feel it would be a wonderful gift to be able to provide people with the option to have hearing.

The cochlea, a spiral tube structure in the inner ear, enables us to hear and distinguish different sound frequencies. Low-frequency regions of the cochlea have longer stereocilia while high-frequency regions have shorter stereocilia. When sound travels through the ear, fluid in the cochlea vibrates, causing the hair cell stereocilia to vibrate. These hair cells send signals to neurons, which pass on information about the sounds to the brain.

Manor previously discovered that the EPS8 protein is essential for normal hearing function because it regulates the length of hair cell stereocilia. Without EPS8, the hairs are very short. Concurrently, co-senior author Walter Marcotti, professor at the University of Sheffield, discovered that in the absence of EPS8 the hair cells also do not develop properly.

For this study, Manor and Marcotti joined forces to see if adding EPS8 to stereocilia hair cells could restore their function to ultimately improve hearing in mice. Using a virus to help deliver the protein to hair cells, the team introduced EPS8 into the inner ears of deaf mice who lacked EPS8. They then used detailed imaging to characterize and measure the hair cell stereocilia.

The team found that EPS8 increased the length of the stereocilia and restored hair cell function in low-frequency cells. They also found that after a certain age, the cells seemed to lose their ability to be rescued by this gene therapy.

EPS8 is a protein with many different functions, and we still have a lot more to uncover about it, says Manor. I am committed to continuing to study hearing loss and am optimistic that our work can help lead to gene therapies that restore hearing.

Future research will include looking at how well EPS8 gene therapy might work to restore hearing during different developmental stages, and whether it might be possible to lengthen the therapeutic window of opportunity.

Other authors on the study are Colbie Chinowsky, Tsung-Chang Sung and Yelena Dayn of Salk; Jing-Yi Jeng, Adam Carlton, Federico Ceriani and Stuart Johnson of the University of Sheffield; Richard Goodyear and Guy Richardson of the University of Sussex; and Steve Brown and Michael Bowl of the MRC Harwell Institute.

The research was supported by the Biotechnology and Biological Sciences Research Council (BB/S006257/1, BB/T016337/1), Waitt Foundation, Grohne Foundation, National Institutes of Health (CA014195, R21DC018237), National Science Foundation (NeuroNex Award 2014862), Chan-Zuckerberg Initiative (Imaging Scientist Award) and Dudley and Geoffrey Cox Charitable Trust.

DOI: 10.1016/j.omtm.2022.07.012

More:
Discovery advances the potential of gene therapy to restore hearing loss - Salk Institute