Category Archives: Genetic medicine

Because CRISPR applications promise so many benefits, we are impatient to see them realized. Indeed, we may complain that the development of CRISPR therapies is too slow. Nonetheless, a handful of CRISPR therapies have advanced to the early stages of clinical trials, including therapies for sickle-cell anemia, HIV disease, and acute myeloid leukemia.

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We are eager to see CRISPR succeed not just in medicine, but in other application areas where humanity faces serious challengesareas that include crop production, bioenergy, manufacturing, and environmental remediation. To hasten progress in all these areas, scientists are working diligently to add tools to the CRISPR toolbox.

Were starting to see CRISPR-edited agricultural products now, Doudna noted. Well see many more over the coming years addressing issues like food security, drought and flood tolerance, reducing pesticide and fertilizer use, eliminating agricultural emissions, as well as carbon removal and sequestration.

For all of the uncertainty that lies ahead, one thing we can all be sure about is that CRISPR will likely have a role in shaping the future of individuals and the planet.

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CRISPR is 10: A decade of gene editing refinements presents new ways to address agricultural diseases thought to be incurable - Genetic Literacy...

- Recipients include 15 individuals living with Duchenne and five siblings in Duchenne families

CAMBRIDGE, Mass., Sept. 07, 2022 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc.(NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced twenty recipients of Route 79, The Duchenne Scholarship Program for the 2022-2023 academic year. The Program was created in 2018 to recognize exceptional individuals living with Duchenne muscular dystrophy as they pursue their post-secondary education. Now in its fifth year, the Program was expanded to include siblings of individuals with Duchenne in recognition of the impact that a diagnosis of Duchenne may have on the entire family. Recipients of the scholarship are chosen by an independent selection committee composed of Duchenne community members, who consider each applicants community involvement and personal essay. Each student will receive a scholarship of up to $5,000.

On behalf of Sarepta and the selection committee, we are thrilled to announce the recipients of Route 79, The Duchenne Scholarship Program, for the 2022-2023 academic year. These twenty outstanding students are exemplary in their commitment and dedication to their studies. In addition to conveying their intellectual curiosity, the essays from this years recipients spoke to the power and strength of community and the importance of advocating for growth and change at a personal and societal level, said Diane Berry, senior vice president, Global Health Policy, Government and Patient Affairs, Sarepta. We are honored to support these young adults as they pursue their educational goals, and we wish them great success in the school year ahead and wherever their academic journey takes them.

2022 Recipients Individuals Living with Duchenne

Porter Aydelotte, California State University, Long Beach

Jared Conant, University of Southern Maine

Aiden Fecteau, Eastern Connecticut State University

Bryson Foster, University of North Carolina, Charlotte

Yuvaraj Gambhir, University of Pennsylvania

Maanav Gupta, University of Houston

Ethan Higginbotham, Wichita State University

Elliott Johnson, Lebanon Valley College

Joshua Jurack, James Madison University

John McConnell, Boise State University

Josh Pflueger, Texas Christian University

Robert Sullivan, John Carroll University

Tayjus Surampudi, Harvard University

Joseph Ware, Liberty University

Jack Wolf, University of Akron, Main Campus

2022 Recipients Siblings in Duchenne Families

Luke Kieser, Indiana Institute of Technology

Grace Lee, University of San Diego

Zoie Liska, Wichita State University

Dylan Malone, University of Mississippi Medical Center

Reese Manderfield, University of Iowa

In addition to application review by the independent committee, submissions are de-identified for the voting panel with no indication of whether the candidate has received, or plans to receive, a Sarepta therapy.

AboutRoute 79, TheDuchenne Scholarship Program

Route 79, TheDuchenne Scholarship Program is designed to help students with Duchenne and siblings of individuals living with Duchenne pursue their post-secondary educational goals. There are 79 exons in the dystrophin gene impacted by Duchenne, and the route traveled by every person impacted by Duchenne is distinct. Sareptas goal through this program is to acknowledge and support individuals with Duchenne and their siblings, who are mapping out their future via educational pursuits.Scholarship recipients are chosen by an independent committee of Duchenne community members based on an applicants community involvement, personal essay, and recommendation letter. Additional information is available at https://www.sarepta.com/route79.

About Sarepta Therapeutics

Sarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophies (LGMDs), and we currently have more than 40 programs in various stages of development. Our vast pipeline is driven by our multi-platform Precision Genetic Medicine Engine in gene therapy, RNA and gene editing. For more information, please visit http://www.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.

Internet Posting of Information

We routinely post information that may be important to investors in the 'For Investors' section of our website atwww.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Source: Sarepta Therapeutics, Inc.

Investor Contact:

Ian Estepan, 617-274-4052

iestepan@sarepta.com

Media Contact:

Tracy Sorrentino, 617-301-8566

tsorrentino@sarepta.com

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Sarepta Therapeutics Announces Recipients of Route 79, The Duchenne Scholarship Program, for ... - The Bakersfield Californian

Experts discuss solving the EHR-compatibility puzzle in point-of-care trials.

Editors note: Industry recognition for the clinical research as a care option, or CRAACO, movement goes to The Conference Forum, which has hosted the conference of the same name, for seven years. This years CRAACO event was held Sept. 12 and Applied Clinical Trials, at the time of this writing, is looking forward to attending and learning more from many of the speakers featured in this article.

At the Icahn School of Medicine at Mount Sinai, researchers are laying the groundwork for future massive genotype-based studies. Within three to six years, the database is expected to hold the sequenced DNA samples of one million peopleall patients of the Mount Sinai Hospital System.

In Oregon and California, researchers wanted to see if people who were overdue for a colon cancer screening test would take one if they were mailed a FIT test. It took one year to identify 41,193 people in 26 federally qualified health clinics.1

And in the Northwell Health System, researchers culled their electronic health record (EHR) system for patients with specific COVID-19 symptoms to help them determine whether the use of famotidine would shorten the number of days a COVID patient contended with symptoms. They found 55 fitting the bill within six weeks.2

At the University of California, San Francisco, and across the country at Temple University Hospital, oncologist researcher Laura Esserman, MD, MBA, and pulmonologist Gerard Criner, MD, respectively, have been using their EHR systems for years to run pragmatic trials and to find eligible clinical trial patients in their respective clinics.3,4 Once found, the medical teams embed the trial into patient care.

If you are wondering if this article concerns EHRs and compatibility, youd be correct. If you are thinking it concerns ways in which clinical trials can be run with less money and fewer data points, youd also be accurate. And if you think its about improving patient care where they receive careall while advancing researchyou are spot on.

What these researchers are doing bears little resemblance to the classic, rigidly run, interventional clinical trial. Trial phases blend into one another. In some cases, molecules under inspection that arent working are eliminated as early as possible from the trial; molecules that do work are tested under more scrutiny. With clinical trials, time means money.

A key point: All enrolled patients were found after serious mining into the providers EHR. So yes, point of care works in large healthcare establishments, with fluid EHR systems. So yes again, point of care is not a routine approach in most trials. A serious problem, says Amy Cramer, director of global product development strategic partnerships at Pfizer and the steering committee board co-chair for the HL7 FHIR Accelerator Vulcan, is that most trials are still conducted using paper processes. Researchers need the data before the trial is started, she adds.

It is all about the technology, Christina Brennan, MD, vice president, clinical research at Northwell Health, tells Applied Clinical Trials. We wouldnt have been able to do [the famotidine trial] without the EHR system, she says. Everything Northwell could determine about its potential recruitment prospects came from its system, as did all inputted data that led to results. We screened thousands of patients for eligibility.

At Temple University Hospital, running trials and treating patients have gone hand in hand for a few years. Our clinical research program is not separate from our clinical care or our academic mission, said Criner, also chair and professor, Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University; and director, Temple Lung Center, in a published interview3, who also reviewed this included information for accuracy. If you embed it into your care program and your care program has to address what the needs of the patient community you treat are, you cant help but make everything betteryour research, clinical care, and training.

As to what this clinical trial approach is called, there is no universal name. Brennan says she didnt think point of care was applicable, and preferred clinical research as a care option, or precision/personalized medicine.

According to FDAwhich, by the way, is a big supporter of embedding clinical research at the point of carePoint of care trials take place in a clinical practice environment and make use of clinical infrastructure and personnel for trial-related activities. A successful trial, an agency spokesperson continued, may shorten the time needed to obtain safety and efficacy data for medical products.

But do not think these trials are allowed to confuse real-world data (RWD) with real-world evidence (RWE). FDA, in its 2018 framework document,5 defined RWD as the data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources, and RWE is the clinical evidence regarding a medical products use and potential benefits or risks derived from analysis of RWD.

Says researcher Rachele Hendricks-Sturrup, DHSc, research director for real-world evidence at the Margolis Health Center at Duke University: Healthcare data is not real-world evidence until it is combined with real-world data.

Taking the 30,000-foot view, Jodyn Platt, PhD, MPH, an assistant professor of learning health sciences at the University of Michigan, says health care should be viewed as a point of learning. Theres a fine line between quality improvement and research in order to learn from that data to give better care.

But it could be worth it, Platt says. If researchers have the opportunity to use a system that allows them to see what is done correctly or not, we have the potential for making the [healthcare system] better for everyone, she says. If we can think strategically, we can make the process better.

Esserman, who built her approach to breast cancer trials in the early 2010s, described how the process works at the UCSF Breast Cancer Center. All registration data are collected and cleaned within 24 hours.4

Each patients information regarding response to the therapy is used to build on to the next patient. This is all about finding early indicators of response and eliminating data detritus, which, says Esserman, clouds results.

The idea, she adds, is to have real-time data collection. All data sets must be complete before randomization, Platt says. We are trying to focus on the data that inform the primary endpoints, so that we are less burdened with data of ancillary interest.

She elaborates that most data, 90%, collected in trials is irrelevant because it is never used or not germane to the primary endpoint. And since all data collection requires time and money, more thoughtful decisions about what to collect matters.

It is a model other are adopting or participating in, including FDA and the National Cancer Institute.7

In Northwells double-blind, placebo-controlled study on famotidine, researchers collected 1,358 data points from 55 patients with COVID; one arm got the famotidine, the other, placebo. Those in the control arm improved three days more quickly. All samples and all treatment were administered in the patients homes. The cost of the trial was less than $1.5 million.2 The success of the study and its cheaper cost have convinced Northwell that the model is worth incorporating into their trial formats. Along with this more patient-centric approach, Brennan says that hybrid trials are being requested more by sponsors.

Between 2014 through 2016, Mount Sinai used EHRs to find 2,050 patients of West-African ancestry with hypertension, no chronic kidney disease, and genotyped them for the APOL1 risk variant, which could be deadly for those subgroups.6 Once patients were found through the EHRs, study coordinators mailed invitations and then followed up with phone calls of those who declined, and intercepted potentially eligible patients at clinics when they were hard to reach, according to the study. The point of the trial was to quickly return genetic results to a randomized group to see how patient outcomes would be affected.

The intervention group reduced their blood pressure and adopted more healthy behaviors. The high-risk patients dropped their systolic blood pressure by 3.6%; the controls dropped by 1.3%.

These results may support an approach of broad implementation of genetic medicine in primary care for certain use cases, concluded Girish N. Nadkarni, MD, MPH, Irene and Dr. Arthur M. Fishberg professor of Medicine, Icahn School of Medicine at Mount Sinai, et al., in the study.6

As to the question of just how common point of care trial research actually is, everyone interviewed had the same answerit isnt.

There is a lot of activity in this space. But it is fragmented, as is our healthcare system, says Platt. Her specialty is studying trust in the US healthcare system. Developing measures of trust to monitor how trial enrollees are faring is in the works, she she adds. It is a huge issue because of digital care in the home. What happens to the data if third parties are involved, or if a startup company that was monitoring patient progress dissolves? How does your data live with this? asks Platt.

She and her staff are starting research in artificial intelligence and how patients trust the technology in their healthcare systems. That is a key research questionits a new form of technology that has little oversight, from institutions and government. We need to understand what the public feels like when they have a stake in the field.

In May, the Duke University Margolis Center for Health Policy published a white paper on point of care-incorporated trials.8 It defined one aspect of the point-of-care scenario as: Using an EHR for enrollment, data collection, and randomization; running the trial where patient care occurs; and combining research and clinical care delivery workflows. The focus is on the trial participants, says Hendricks-Sturrup, a co-author. We want to achieve better screening, consent, randomization, and data collection, then incorporating those finds into routine care.

The difference between other trial designs and those that use point of care, says Hendricks-Sturrup, is that point of care is designed to know if the therapy is efficacious across all populations.

Margolis is working to resolve issues that could impede point-of-care progress, such as who runs the trial, who should pay for it, and how can data be collected and handled in an easy fashion across different systems? A major point is not adding burden to providers. We are working to tackle policy, says Trevan Locke, PhD, assistant research director for Margolis.

As for the blip, researchers for the colon cancer screening trial learned that buy-in from staff involved in the trial is essential. Staff at the various federally qualified health clinics didnt all do as the researchers asked, like installing a piece of software into their EHRs to find and track possible participants. Researchers stated: For most of the participating health centers, [this trial] represented the first time EHR tools were used to deliver cancer screening services outside the clinic. Implementation might have increasedwith experience.1

Alexander Charney, MD, PhD, associate professor, departments of psychiatry and genetics and genomic sciences, and co-director of the Mount Sinai Million Health Discoveries Program, says that as it acquires patient samples, it is gaining approvals for future trials. No studies are established yet, he says.

But lets fast-forward five years, Charney continues. A sponsor wants to run a trial comparing therapy X to therapy Y, when half of the patients have a certain genetic variant. If a researcher wants to do that trial, five years from now, patients will already have consented, he adds. We have laid the groundwork.

All 17 hospitals and clinics in the Mount Sinai Health System will be recruiting for this project, which is being underwritten by Regeneron. The volume of patients and unification of Mount Sinais operations make the enrollment goal possible, says Charney. His fellow co-director, Nadkarni, says enrollment is going slowly for a purpose.

We want to make sure systems are good to go, he tells Pharm Exec, and that safeguards are working, like ensuring patients are not duplicated in the system. The platform, he notes, meets all NIH and Department of Defense security standards.

Partnering with Regeneron, says Charney, was key to getting the project off the ground. There is no other way to sequence the genome of one million people, he adds. Regeneron, notes Nadkarni, will sequence the DNA samples, and then return the patient data.

At Northwell, Brennan said that as each trial request comes in, the team is looking at whether an embedded study can work. Of the 2,000 trials in motion, 5% to 8% are designed as a hybrid approach. Despite all the talk about embedded, i.e., point of care, few are being run that way.

But, she adds, We dont want to go back to the former ways and traditional methods of running a trial. When we saw how to pivot in COVID, we were able to [be flexible].

Christine Bahls is a freelance writer for medical, clinical trials, and pharma information.

Excerpt from:
'Record' Gains in Bringing Research Closer to the Patient - Applied Clinical Trials Online

EMERYVILLE, Calif.--(BUSINESS WIRE)--Metagenomi, a gene editing company with a versatile portfolio of next-generation CRISPR gene editing tools, today announced its participation in the following investor and industry conferences:

Citis 17th Annual BioPharma ConferenceCompany Panel titled Private Co-Panel: Genetic Medicine on September 7, 4:20 - 5:05 p.m. EDT11 meetings with institutional investorsParticipants: Brian C. Thomas, Ph.D., CEO and founder, and Simon Harnest, CIO, SVP Strategy

Wells Fargo Healthcare ConferenceCorporate presentation with Q&A on September 9, 10:25 - 10:55 a.m. EDT11 meetings with institutional investorsParticipants: Brian C. Thomas, Ph.D., CEO and founder, and Simon Harnest, CIO, SVP Strategy

Bairds 2022 Global Healthcare ConferenceCorporate presentation with Q&A on September 13, 9:40 - 10:10 a.m. EDTParticipant: Simon Harnest, CIO, SVP Strategy

GENedges GEN The State of Biotech Virtual SummitPre-recorded presentation, September 21-22Participant: Brian C. Thomas, Ph.D., CEO and founder

Jefferies Cell and Genetic Medicine SummitCorporate presentation with Q&A on September 3011 meetings with institutional investorsParticipant: Simon Harnest, CIO, SVP Strategy

About Metagenomi

Metagenomi is a gene editing company committed to developing potentially curative therapeutics by leveraging a proprietary toolbox of next-generation gene editing systems to accurately edit DNA where current technologies cannot. Our metagenomics-powered discovery platform and analytical expertise reveal novel cellular machinery sourced from otherwise unknown organisms. We adapt and forge these naturally evolved systems into powerful gene editing systems that are ultra-small, extremely efficient, highly specific and have a decreased risk of immune response. These systems fuel our pipeline of novel medicines and can be leveraged by partners. Our goal is to revolutionize gene editing for the benefit of patients around the world. For more information, please visit https://metagenomi.co/.

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Metagenomi Announces Participation in September Investor and Industry Conferences - Business Wire

Sarepta Therapeutics, Inc.

CAMBRIDGE, Mass., Sept. 06, 2022 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has removed the clinical hold on SRP-5051 (vesleteplirsen), the Companys investigational, next-generation peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) to treat patients with Duchenne muscular dystrophy who are amenable to exon 51 skipping. After discussions with FDA and as part of the lift, Sarepta will adjust the global trial protocol to include expandedmonitoringof urine biomarkers.

The hold in Part B of Study 5051-201, also known as MOMENTUM, followed a serious adverse event of hypomagnesemia. Information was provided by the Company to FDA to assess the adequacy of the risk mitigation and safety monitoring plan.

We would like to thank FDA for working closely with us to expeditiously resolve this clinical hold. We will implement the changes in the protocol to resume dosing in the U.S. as quickly as possible, said Louise Rodino-Klapac, Ph.D., executive vice president and chief scientific officer, Sarepta Therapeutics. Our monitoring plan is designed to mitigate the risks of hypomagnesemia. MOMENTUM has continued enrolling participants outside the U.S., and we remain on track to complete enrollment by the end of 2022. Sarepta is committed to the SRP-5051 program and excited about the PPMO platform as a next-generation exon-skipping approach for the treatment of Duchenne.

About SRP-5051 (vesleteplirsen) SRP-5051 is an investigational agent using Sareptas PPMO chemistry and exon-skipping technology to skip exon 51 of the dystrophin gene. SRP-5051 is designed to bind to exon 51 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for production of an internally shortened, functional dystrophin protein. PPMO is Sareptas next-generation chemistry platform designed around a proprietary cell-penetrating peptide conjugated to the PMO backbone, with the goal of increasing tissue penetration, increasing exon skipping, and significantly increasing dystrophin production. Around 13% of DMD patients have mutations that make them amenable to skipping exon 51. If successful, the PPMO offers the potential for improved efficacy and less frequent dosing for patients.

Story continues

About MOMENTUM (Study SRP-5051-201) MOMENTUM is a Phase 2, multi-arm, ascending dose trial of SRP-5051, infused monthly and will assess dystrophin protein levels in skeletal muscle tissue following SRP-5051 treatment. The trial will enroll up to 60 participants, both ambulant and non-ambulant, between the ages of 7 to 21 at sites in the U.S., Canada, and the European Union. The trial will also assess safety and tolerability.

In 2021, the Company announced results from Part A of MOMENTUM showing that after 12 weeks, 30 mg/kg of SRP-5051 dosed monthly resulted in 18 times the exon skipping and eight times the dystrophin production as eteplirsen, dosed weekly for 24 weeks. Reversible hypomagnesemia was identified in patients taking SRP-5051. The protocol for Part B of MOMENTUM includes magnesium supplementation and monitoring of magnesium levels.

More information can be found on http://www.clinicaltrials.gov.

About Sarepta TherapeuticsSarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophies (LGMDs), and we currently have more than 40 programs in various stages of development. Our vast pipeline is driven by our multi-platform Precision Genetic Medicine Engine in gene therapy, RNA, and gene editing. For more information, please visitwww.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.

Internet Posting of InformationWe routinely post information that may be important to investors in the 'For Investors' section of our website atwww.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Forward-Looking StatementsThis press release contains "forward-looking statements." Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "possible" and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements regarding adjustments to our global trial protocol for SRP-5051; the potential benefits of PPMO and SRP-5051; our approach to monitoring and managing hypomagnesemia; and our expected timelines, plans, and milestones, including completing enrollment of Part B of MOMENTUM by the end of 2022, and resuming screening and dosing in the U.S. as quickly as possible.

These forward-looking statements involve risks and uncertainties, many of which are beyond our control. Known risk factors include, among others: success in preclinical studies and clinical trials, especially if based on a small patient sample, does not ensure that later clinical trials will be successful, and may not be consistent with the final data set and analysis thereof or result in a safe or effective treatment benefit; different methodologies, assumptions and applications we utilize to assess particular safety or efficacy parameters may yield different statistical results, and even if we believe the data collected from clinical trials of our product candidates are positive, these data may not be sufficient to support approval by the FDA or foreign regulatory authorities; we may not be able to execute on our business plans and goals, including meeting our expected or planned regulatory milestones and timelines, clinical development plans, and bringing our product candidates to market, due to a variety of reasons, some of which may be outside of our control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, regulatory, court or agency decisions, such as decisions by the United States Patent and Trademark Office with respect to patents that cover our product candidates and the ongoing COVID-19 pandemic; and those risks identified under the heading Risk Factors in Sareptas most recent Annual Report on Form 10-K for the year ended December 31, 2021, and most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by the Company, which you are encouraged to review.

Any of the foregoing risks could materially and adversely affect the Companys business, results of operations and the trading price of Sareptas common stock. For a detailed description of risks and uncertainties Sarepta faces, you are encouraged to review the SEC filings made by Sarepta. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. Sarepta does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof.

Source: Sarepta Therapeutics, Inc.

Investor Contact: Ian Estepan, 617-274-4052iestepan@sarepta.com

Media Contact: Tracy Sorrentino, 617-301-8566tsorrentino@sarepta.com

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Sarepta Therapeutics Announces That FDA has Lifted its Clinical Hold on SRP-5051 for the Treatment of Duchenne Muscular Dystrophy - Yahoo Finance

Researchers have identified genetic signatures that may explain the ethnic differences in the severity of prostate cancer, particularly in sub-Saharan Africa.

In two studies published in Nature and Genome Medicine, researchers detailed how they used genetic sequencing of prostate cancer tumors from Australian, Brazilian, and South African donors to identify a new prostate cancer taxonomy and cancer drivers that not only distinguish patients by genetic ancestry, but also predict which cancers are likely to become life-threatening.

Our understanding of prostate cancer has been severely limited by a research focus on Western populations, said senior author Vanessa Hayes, genomicist and Petre Chair of Prostate Cancer Research at the University of Sydneys Charles Perkins Centre and Faculty of Medicine and Health in Australia. Being of African descent, or from Africa, more than doubles a mans risk for lethal prostate cancer. While genomics holds a critical key to unravelling contributing genetic and non-genetic factors, data for Africa has till now, been lacking.

In the Nature study, the researchers used whole-genome sequencing of treatment-nave prostate cancer samples from 183 ancestrally and globally distinct patients. They generated a large cancer genomics resource for sub-Saharan Africa, identifying around 2 million somatic variants.

We found Africans to be impacted by a greater number and spectrum of acquired (including cancer driver) genetic alterations, with significant implications for ancestral consideration when managing and treating prostate cancer, said Hayes.

Among the significant findings were elevated tumor mutational burden, increased percentage of genome alteration, a greater number of predicted damaging mutations, and a higher total of mutational signatures. Additionally, they identified driver genes NCOA2, STK19, DDX11L1, PCAT1 and SETBP1.

In the Genome Medicine study, the researchers used whole genome sequencing and best practice workflows to analyze structural variations for 180 prostate tumors derived from 115 African, 61 European, and four ancestrally admixed patients.

In African-derived tumors there was a 1.6- to 2.5-fold increase in duplication events. African-derived tumors were also twofold more likely to present with a hyper-SV subtype.

Through African inclusion, we have made the first steps not only towards globalizing precision medicine but ultimately to reducing the impact of prostate cancer mortality across rural Africa, explains University of Pretorias Professor Riana Bornman, an international expert in mens health and clinical lead for the Southern African Prostate Cancer Study in South Africa.

References

Study reveals aggressive prostate cancer linked to ancestral heritage

African-specific molecular taxonomy of prostate cancer

Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers

See the article here:
Studies Reveal Aggressive Prostate Cancer Linked to Ancestral Heritage - DocWire News

Manufacturing partner, Lonza, has today (September 6) announced a collaboration with Touchlight, a biotech company that works with enzymatic DNA production enabling genetic medicine.

Through this collaboration, Lonza says it will have the ability to expand it end-to-end offering for mRNA manufacturing with an additional source of DNA raw material. This material comes from Touchlights doggybone DNA (dbDNA). Touchlight says it will be able to widen the channels making it easier for customers to get to the dbDNA technology.

The company developed thesynthetic DNA vector, known as doggybone -named after its schematic structure DNA or dbDNA and enzymatic manufacturing process, which they say enables them to produce DNA at unprecedented speed, scale and purity.

Lonzas customers will be able to access the enzymatic DNA technology; a linear, covalently closed DNA vector, produced using an enzymatic manufacturing process which enables GMP production.

Access to this technology, the companies say, will expand the options for Lonzas customers beyond the traditional method of working with plasmid DNA (pDNA), while continuing to benefit from the Lonzas integrated mRNA manufacturing offering.

Andr Goerke, vice president, business unit head mRNA, Lonza, said: The strategic collaboration with Touchlight enables Lonza to further enhance its position as a global leader in mRNA manufacturing.

We can now provide our customers with a strong foundation to deliver an end-to-end offering that includes access to a novel synthetic DNA technology. Such an integrated solution can prove beneficial in speeding up time to market, which is critical in the fast-paced industry of mRNA manufacturing.

DNA serves as the starting template for the production of mRNA. Through an enzymatic in vitro transcription process, this DNA sequence is then transcribed into a single-stranded RNA molecule, which is then processed into mRNA. Current mRNA-based therapeutics in development include vaccines for infectious diseases and immuno-oncology.

Karen Fallen, CEO, Touchlight DNA services, added: We are delighted to provide Touchlight customers the benefits of an end-to-end mRNA offering through our collaboration with Lonza. Lonza is the leading CDMO in mRNA manufacturing and has an established, global mRNA manufacturing network. The alliance allows both companies to innovate and to extend their offering on a global level.

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Lonza and Touchlight collaboration will expands customer's access to DNA - Labiotech.eu

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Eight months after falling ill with covid-19, the 73-year-old woman couldnt remember what her husband had told her a few hours before. She would forget to remove laundry from the dryer at the end of the cycle. She would turn on the tap at a sink and walk away.

Before covid, the woman had been doing bookkeeping for a local business. Now, she couldnt add single-digit numbers in her head.

Was it the earliest stage of dementia, unmasked by covid? No. When a therapist assessed the womans cognition, her scores were normal.

What was going on? Like many people whove contracted covid, this woman was having difficulty sustaining attention, organizing activities, and multitasking. She complained of brain fog. She didnt feel like herself.

But this patient was lucky. Jill Jonas, an occupational therapist associated with the Washington University School of Medicine in St. Louis who described her to me, has been providing cognitive rehabilitation to the patient, and she is getting better.

Cognitive rehabilitation is therapy for people whose brains have been injured by concussions, traumatic accidents, strokes, or neurodegenerative conditions such as Parkinsons disease. Its a suite of interventions designed to help people recover from brain injuries, if possible, and adapt to ongoing cognitive impairment. Services are typically provided by speech and occupational therapists, neuropsychologists, and neurorehabilitation experts.

In a recent development, some medical centers are offering cognitive rehabilitation to patients with long covid (symptoms that persist several months or longer after an infection that cant be explained by other medical conditions). According to the Centers for Disease Control and Prevention, about 1 in 4 older adults who survive covid have at least one persistent symptom.

Experts are enthusiastic about cognitive rehabilitations potential. Anecdotally, were seeing a good number of people [with long covid] make significant gains with the right kinds of interventions, said Monique Tremaine, director of neuropsychology and cognitive rehabilitation at Hackensack Meridian Healths JFK Johnson Rehabilitation Institute in New Jersey.

Among the post-covid cognitive complaints being addressed are problems with attention, language, information processing, memory, and visual-spatial orientation. A recent review in JAMA Psychiatry found that up to 47% of patients hospitalized in intensive care with covid developed problems of this sort. Meanwhile, a new review in Nature Medicine found that brain fog was 37% more likely in nonhospitalized covid survivors than in comparable peers who had no known covid infections.

Also, theres emerging evidence that seniors are more likely to experience cognitive challenges post-covid than younger people a vulnerability attributed, in part, to older adults propensity to have other medical conditions. Cognitive challenges arise because of small blood clots, chronic inflammation, abnormal immune responses, brain injuries such as strokes and hemorrhages, viral persistence, and neurodegeneration triggered by covid.

Getting help starts with an assessment by a rehabilitation professional to pinpoint cognitive tasks that need attention and determine the severity of a persons difficulties. One person may need help finding words while speaking, for instance, while another may need help with planning and yet another may not be processing information efficiently. Several deficits may be present at the same time.

Next comes an effort to understand how patients cognitive issues affect their daily lives. Among the questions that therapists will ask, according to Jason Smith, a rehabilitation psychologist at the University of Texas Southwestern Medical Center in Dallas: Is this [deficit] showing up at work? At home? Somewhere else? Which activities are being affected? Whats most important to you and what do you want to work on?

To try to restore brain circuits that have been damaged, patients may be prescribed a series of repetitive exercises. If attention is the issue, for instance, a therapist might tap a finger on the table once or twice and ask a patient to do the same, repeating it multiple times. This type of intervention is known as restorative cognitive rehabilitation.

It isnt easy because its so monotonous and someone can easily lose attentional focus, said Joe Giacino, a professor of physical medicine and rehabilitation at Harvard Medical School. But its a kind of muscle building for the brain.

A therapist might then ask the patient to do two things at once: repeat the tapping task while answering questions about their personal background, for instance. Now the brain has to split attention a much more demanding task and youre building connections where they can be built, Giacino continued.

To address impairments that interfere with peoples daily lives, a therapist will work on practical strategies with patients. Examples include making lists, setting alarms or reminders, breaking down tasks into steps, balancing activity with rest, figuring out how to conserve energy, and learning how to slow down and assess what needs to be done before taking action.

A growing body of evidence shows that older adults can learn to use these strategies and that it does, in fact, enhance their everyday life, said Alyssa Lanzi, a research assistant professor who studies cognitive rehabilitation at the University of Delaware.

Along the way, patients and therapists discuss what worked well and what didnt, and practice useful skills, such as using calendars or notebooks as memory aids.

As patients become more aware of where difficulties occur and why, they can prepare for them and they start seeing improvement, said Lyana Kardanova Frantz, a speech therapist at Johns Hopkins University. A lot of my patients say, I had no idea this [kind of therapy] could be so helpful.

Johns Hopkins has been conducting neuropsychiatric exams on patients who come to its post-covid clinic. About 67% have mild to moderate cognitive dysfunction at least three months after being infected, said Dr. Alba Miranda Azola, co-director of Johns Hopkins Post-Acute COVID-19 Team. When cognitive rehabilitation is recommended, patients usually meet with therapists once or twice a week for two to three months.

Before this kind of therapy can be tried, other problems may need to be addressed. We want to make sure that people are sleeping enough, maintaining their nutrition and hydration, and getting physical exercise that maintains blood flow and oxygenation to the brain, Frantz said. All of those impact our cognitive function and communication.

Depression and anxiety common companions for people who are seriously ill or disabled also need attention. A lot of times when people are struggling to manage deficits, theyre focusing on what they were able to do in the past and really mourning that loss of efficiency, Tremaine said. Theres a large psychological component as well that needs to be managed.

Medicare usually covers cognitive rehabilitation (patients may need to contribute a copayment), but Medicare Advantage plans may differ in the type and length of therapy theyll approve and how much theyll reimburse providers an issue that can affect access to care.

Still, Tremaine noted, not a lot of people know about cognitive rehabilitation or understand what it does, and it remains underutilized. She and other experts dont recommend digital brain-training programs marketed to consumers as a substitute for practitioner-led cognitive rehabilitation because of the lack of individualized assessment, feedback, and coaching.

Also, experts warn, while cognitive rehabilitation can help people with mild cognitive impairment, its not appropriate for people who have advanced dementia.

If youre noticing cognitive changes of concern, ask for a referral from your primary care physician to an occupational or speech therapist, said Erin Foster, an associate professor of occupational therapy, neurology, and psychiatry at Washington University School of Medicine in St. Louis. Be sure to ask therapists if they have experience addressing memory and thinking issues in daily life, she recommended.

If theres a medical center in your area with a rehabilitation department, get in touch with them and ask for a referral to cognitive rehabilitation, said Smith, of UT Southwestern Medical Center. The professional discipline that helps the most with cognitive rehabilitation is going to be rehabilitation medicine.

Judith Graham, a contributing columnist, writes the Navigating Aging column for KHN. She has covered health care for more than 30 years. Find Judith on Twitter @judith_graham

This story was produced byKHN, which publishesCalifornia Healthline, an editorially independent service of theCalifornia Health Care Foundation.

KHN(Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs atKFF(Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation. Find KHN on Twitter@KHNews

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Elderly are more affected by COVID brain fog, but 'cognitive rehab' could be an effective treatment - Genetic Literacy Project

An Inserm team at the Lille Neuroscience & Cognition laboratory (Inserm/Universit de Lille, Lille University Hospital) has joined forces with its counterparts at Lausanne University Hospital (CHUV) to test the efficacy of GnRH injection therapy in order to improve the cognitive functions of a small group of patients with Down syndrome. First the scientists revealed a dysfunction of the GnRH neurons in an animal model of Down syndrome and its impacts on the cognitive function impairment associated with the condition. Then a pilot study testing GnRH pulsatile injection therapy was conducted in seven patients. The results were promising : the therapy led to improved cognitive function and brain connectivity. This study has been published in Science.

Down syndrome, also known as trisomy 21, affects around one in 800 births and results in a variety of clinical manifestations, including decline in cognitive capacity. With age, 77% of people with the condition experience symptoms similar to those of Alzheimer's disease. Gradual loss of the ability to smell, typical of neurodegenerative diseases, is also commonly encountered from the prepubertal period, with potential sexual maturation deficits occurring in men.

GnRH-secreting neuron dysfunction identified in Down syndrome

Recent discoveries have suggested that the neurons expressing gonadotropin-releasing hormone (GnRH) - which is known for regulating reproduction via the hypothalamus - could also act on other brain regions with a potential role in other functions, such as cognition.

With this idea in mind, the Lille Neuroscience & Cognition laboratory team led by Inserm Research Director Vincent Prvot studied the mechanism which regulates GnRH in mouse models of Down syndrome.

The laboratory demonstrated that five strands of microRNA regulating the production of this hormone - which are found on chromosome 21 are dysfunctional. This supernumerary chromosome then leads to abnormalities in the neurons that secrete GnRH. These findings were confirmed at both genetic and cellular levels. The Inserm scientists were able to demonstrate that the progressive cognitive and olfactory deficiencies seen in the mice were closely linked to dysfunctional GnRH secretion.

Restoring GnRH production to restore cognitive function

The Inserm scientists were then able to demonstrate that restoring physiological GnRH system function restores cognitive and olfactory functions in trisomic mice.

These findings in mice were discussed with Nelly Pitteloud, professor at the Faculty of Biology and Medicine of the University of Lausanne and head of the Endocrinology, Diabetology, and Metabolism Department at CHUV. Her research focuses on congenital GnRH deficiency, a rare disease which manifests by the absence of spontaneous puberty. These patients are given pulsatile GnRH therapy in order to reproduce the natural pulsatile rhythm of this hormones secretion, in order to induce puberty.

The researchers therefore decided to test the efficacy of pulsatile GnRH therapy on cognitive and olfactory deficits in trisomic mice, following a protocol identical to that used in humans. After 15 days, the team was able to demonstrate the restoration of olfactory and cognitive functions in mice.

Pulsatile GnRH therapy improves cognitive function and neural connectivity in a small patient group

The next stage for the scientists and doctors involved a pilot clinical trial in patients to evaluate the effects of this treatment. Seven men with Down syndrome, between 20 and 50years of age, received one subcutaneous dose of GnRH every two hours for 6months via a pump placed on the arm. Cognition and olfactory tests as well as MRI exams were performed before and after the treatment.

From the clinical viewpoint, cognitive performance increased in 6 of the 7 patients with better three-dimensional representation, better understanding of instructions, improved reasoning, attention, and episodic memory. However, the treatment had no impact on the ability to smell. These measures to improve cognitive functions were confirmed by brain imaging conducted by the CHUV Department of Clinical Neurosciences, which revealed a significant increase in functional connectivity.

These data suggest that the treatment acts on the brain by strengthening the communication between certain regions of the cortex."Maintaining the GnRH system appears to play a key role in brain maturation and cognitive functions," explains Prvot. "In Down syndrome, pulsatile GnRH therapy is looking promising, especially as it is an existing treatment with no significant side effects," adds Pitteloud.

These promising findings now justify the launch of a larger study with the inclusion of women to confirm the efficacy of this treatment in people with Down syndrome, but also for other neurodegenerative conditions such as Alzheimer's disease.

Source

GnRH replacement rescues cognition in Down Syndrome

Maria Manfredi-Lozano1,2#, Valerie Leysen1,2#, Michela Adamo3,4#, Isabel Paiva5, Renaud Rovera6, Jean-Michel Pignat7, Fatima Ezzahra Timzoura1,2, Michael Candlish8,, Sabiha Eddarkaoui1, Samuel A. Malone1,2, Mauro S. B. Silva1,2, Sara Trova1,2, Monica Imbernon1,2, Laurine Decoster1,2, Ludovica Cotellessa1,2,Manuel Tena-Sempere9, Marc Claret10, Ariane Paoloni-Giacobino11, Damien Plassard12, Emmanuelle Paccou3, Nathalie Vionnet3, James Acierno3, Aleksandra Maleska Maceski13, Antoine Lutti14, Frank Pfrieger15, S. Rasika1,2, Federico Santoni4, Ulrich Boehm8, Philippe Ciofi16, Luc Bue1, Nasser Haddjeri6, Anne-Laurence Boutillier5, Jens Kuhle13, Andrea Messina3,4, Bogdan Draganski14,17, Paolo Giacobini1,2, Nelly Pitteloud3,4*, Vincent Prevot1,2 *

1 Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, UMR-S 1172, Labex DistAlz,Lille, France2 Laboratory of Development and Plasticity of the Neuroendocrine Brain, FHU 1000 days forhealth, EGID, Lille, France3 Department of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital,1011 Lausanne, Switzerland4 Faculty of Biology and Medicine, University of Lausanne, Lausanne 1005, Switzerland5 Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364, Universit deStrasbourg-CNRS, Strasbourg, France6 Univ. Lyon, Universit Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research InstituteU1208, Bron 69500, France7Department of Clinical Neurosciences, Neurorehabilitation Unit, University Hospital CHUV,Lausanne, Switzerland8 Experimental Pharmacology, Center for Molecular Signaling (PZMS), Saarland UniversitySchool of Medicine, 66421, Homburg, Germany9 Univ. Cordoba, IMIBC/HURS, CIBER Fisiopatologa de la Obesidad y Nutricin, Instituto deSalud Carlos III, Cordoba, Spain10 Neuronal Control of Metabolism Laboratory, Institut d'Investigacions Biomdiques August Pi iSunyer (IDIBAPS), 08036 Barcelona, Spain; Centro de Investigacin Biomdica en Red(CIBER) de Diabetes y Enfermedades Metablicas Asociadas (CIBERDEM), 08036 Barcelona,Spain11Department of Genetic Medicine, University Hospitals of Geneva, 4 rue Gabrielle-Perret-Gentil,1211, Genve, Switzerland12 CNRS UMR 7104, INSERM U1258, GenomEast Platform, Institut de Gntique et de BiologieMolculaire et Cellulaire (IGBMC), Universit de Strasbourg, Illkirch, France13 Neurologic Clinic and Polyclinic, MS Centre and Research Centre for Clinical Neuroimmunologyand Neuroscience Basel; University Hospital Basel, University of Basel, Basel Switzerland14 Laboratory for Research in Neuroimaging LREN, Centre for Research in Neurosciences,Department of Clinical Neurosciences, Lausanne University Hospital and University ofLausanne, Switzerland15 Centre National de la Recherche Scientifique, Universit de Strasbourg, Institut desNeurosciences Cellulaires et Intgratives, 67000 Strasbourg, France16 Univ. Bordeaux, Inserm, U1215, Neurocentre Magendie, Bordeaux, France17 Neurology Department, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig,Germany New address, Institute of Cell Biology and Neuroscience and Buchmann Institute for MolecularLife Sciences (BMLS), University of Frankfurt, Max-von-Laue-Str. 15, 60438, Frankfurt am

Main, Germany

# these authors contributed equally

* these authors contributed equally

Science, September 1, 2022

https://doi.org/10.1126/science.abq4515

Contact details

Vincent Prvot

Inserm Research Director

"Development and Plasticity of the Neuroendocrine Brain" team leader

Unit U1172 Lille Neuroscience & Cognition Lille, France

Email:vincent.prevot@inserm.fr

Telephone number provided upon request

Nelly Pitteloud

Professor at Universit de Lausanne

Head of Department, Endocrinology, Diabetology, and Metabolism, CHUV

Email: nelly.pitteloud@chuv.ch

Press contact

presse@inserm.fr

medias@chuv.ch

GnRH replacement rescues cognition in Down Syndrome

1-Sep-2022

Read more from the original source:
A therapy found to improve cognitive function in patients with Down syndrome - EurekAlert