Category Archives: Gene Medicine

Should you find a link that does not work within any Guidance document, Rule or other document posted on the FDA Web site, please try searching for the document using the document title. If you need further assistance, please go to Contact FDA.

Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products; Draft Guidance for Industry3/2022

Human Gene Therapy Products Incorporating Human Genome Editing; Draft Guidance for Industry3/2022

Policy for Certain REMS Requirements During the Tocilizumab Shortage Related to the COVID-19 Public Health Emergency; Guidance for Industry and Health Care Professionals12/2021

Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations; Guidance for Industry9/2021

Studying Multiple Versions of a Cellular or Gene Therapy Product in an Early-Phase Clinical Trial; Draft Guidance for Industry9/2021

Manufacturing Considerations for Licensed and Investigational Cellular and Gene Therapy Products During COVID-19 Public Health Emergency; Guidance for Industry1/2021

Human Gene Therapy for Neurodegenerative Diseases; Draft Guidance for Industry1/2021

Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs); Guidance for Industry1/2020

Long Term Follow-up After Administration of Human Gene Therapy Products; Guidance for Industry1/2020

Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up; Guidance for Industry1/2020

Human Gene Therapy for Hemophilia; Guidance for Industry1/2020

Human Gene Therapy for Rare Diseases; Guidance for Industry1/2020

Human Gene Therapy for Retinal Disorders; Guidance for Industry1/2020

Evaluation of Devices Used with Regenerative Medicine Advanced Therapies;Guidance for Industry2/2019

Expedited Programs for Regenerative Medicine Therapies for Serious Conditions;Guidance for Industry2/2019

Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use; Guidance for Industry and Food and Drug Administration StaffUpdated: 12/2017

Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception; Guidance for Industry11/2017

Deviation Reporting for Human Cells, Tissues, and Cellular and Tissue-Based Products Regulated Solely Under Section 361 of the Public Health Service Act and 21 CFR Part 1271; Guidance for Industry9/2017

Recommendations for Microbial Vectors Used for Gene Therapy; Guidance for Industry9/2016

Design and Analysis of Shedding Studies for Virus or Bacteria-Based Gene Therapy and Oncolytic Products; Guidance for Industry8/2015

Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Guidance for Industry6/2015

Determining the Need for and Content of Environmental Assessments for Gene Therapies, Vectored Vaccines, and Related Recombinant Viral or Microbial Products; Guidance for Industry3/2015

Guidance for Industry: BLA for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System3/2014. (This guidance finalizes the draft guidance of the same title dated June 2013.)

IND Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System - Guidance for Industry and FDA Staff3/2014. (This guidance finalizes the draft guidance of the same title dated June 2013.)

Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products(This guidance finalizes the draft guidance entitled Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products dated November 2012) 11/2013

Guidance for Industry: Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee Cartilage12/2011. (This guidance finalizes the draft guidance of the same title dated July 2007.)

Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines10/2011. (This guidance finalizes the draft guidance of the same title dated September 2009.)

Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products1/2011. (This guidance finalizes the draft document of the same name, dated October 2008.)

Guidance for Industry: Cellular Therapy for Cardiac Disease(This guidance finalizes the draft guidance entitled Guidance for Industry: Somatic Cell Therapy for Cardiac Disease dated March 2009 (April 2, 2009, 74 FR 14992). 10/2010.

Guidance for Industry: Considerations for Allogeneic Pancreatic Islet Cell Products9/2009

Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs)4/2008

Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products; Guidance for Industry8/2007

Guidance for Industry: Guidance for Human Somatic Cell Therapy and Gene Therapy3/1998

12/10/2021

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Cellular & Gene Therapy Guidances | FDA

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The National Institute on Deafness and Other Communication Disorders (NIDCD) has awarded Xue Zhong Liu, M.D., Ph.D., Marian and Walter Hotchkiss Endowed Chair in Otolaryngology at the University of Miami Miller School of Medicine, a five-year, $3.5 million R01 research grant to develop a precision medicine approach to treat hearing loss (HL) in Usher syndrome (USH).

There is no cure for USH, and current treatments inadequately address this inherited condition that can cause not only HL but also vision loss.

Todays treatment for Usher syndrome is limited to cochlear implants or hearing aids, which help to address the hearing loss, but there is no biological treatment for HL and the blindness. There is an unmet need to develop alternative treatment options, Dr. Liu said.

The NIH grant will fund Miller School research aimed at developing and testing novel therapy approaches with gene editing. Gene editing is a group of technologies that allow scientists to change an organism's DNA. CRISPR-Cas9 is a popular gene editing technology developed to treat genetic disorders.

The Miller School is one of a select few sites in the world conducting research to apply CRISPR/Cas9 gene editing for HL including Usher syndrome, said Dr. Liu, who also is vicechair of the Department of Otolaryngology and professor of otolaryngology, human genetics, biochemistry, and pediatrics at the Miller School.

Gene- and cell-based therapies using genome editing offer the promise of treatment for a variety of inherited disorders but have not been used successfully for human hereditary HL, including Usher syndrome.

Dr. Liu, along with his collaborator Dr. Zheng-Yi Chen from the Massachusetts Eye and Ear Infirmary, Department of Otolaryngology, Harvard Medical School, aim to pave the way for the development of gene therapy approaches that would address HL Usher syndrome patients hearing.

We will use CRISPR/Cas9 to correct mutations in three different Usher genes shown in our preliminary data to cause most inherited hearing loss in USH, he said. This will involve strategies to rescue hearing in transgenic USH mouse models and developing CRISPR/Cas9 editing strategies to disrupt USH mutations, using human inner ear organoids derived from patient-induced pluripotent stem cells.

The NIH-funded study could lead to patient-specific treatment, based on a patients USH genetic mutations. In the meantime, Dr. Liu has developed a collaborating program with the University of Miami Ear Institute and Bascom Palmer Eye Institute to provide better care for people with Usher syndrome.

Recent breakthroughs in genetic screening, gene- or cell-based therapeutics, and gene editing for the inner ear can lead to novel therapies for multiple classes of hereditary hearing loss. We are excited as this is the first gene therapy NIH grant using CRISPR/Cas9 at UM for common sensory disorders, said Fred Telischi, M.D., M.E.E., chair of otolaryngology, professor of neurological surgery and biomedical engineering, and the James R. Chandler Chair in Otolaryngology.

This grant was awarded by the NIDCD as part of its high-impact program to help meet an unmet patient need, Dr. Liu said. Our aim is to lay the foundation for moving genome editing approaches closer to clinical trials on humans with Usher syndrome, which accounts for about 50% of all hereditary deaf-blindness cases, including in children.

The Genetic Hearing Loss Clinic at University of Miami Ear Institute is a multi-disciplinary program that provides diagnostic, molecular testing, genetic counseling, and intervention options for patients and families who are dealing with various types of HL.

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NIH Funds Miller School Researchers Novel Work to Develop Gene Therapy for Hearing Loss-related Usher... - InventUM | University of Miami Miller...

In a clinical trial, the first patient has received a single dose of a new human immunodeficiency virus (HIV) gene editing therapy, researchers at the Lewis Katz School of Medicine at Temple University and Excision BioTherapeutics, Inc have reported.

In a collaborative effort, the researchers are currently running aphase 1/2 clinical trial to evaluate the safety and efficacy of their therapy, calledEBT-101, which is based on gene editing technology known as CRISPR.

Nearly 40 million people worldwide suffer from the effects of HIV, and more than 40 years after the discovery of HIV/AIDS, there still are no curative treatments, said Professor Kamel Khalili, who helped lead the trial, in a statement.

EBT-101 can potentially address long-standing unmet needs of individuals living with HIV/AIDS by removing viral DNA from their cells, thereby eradicating infection.

When HIV infects, it takes long-term hold and hides from the immune system in cells, compromising the patient's immunity over time and eventually leading to the development of AIDS the progressive failure of a patient's immune system. There is currently no cure for HIV, but various treatments and medications can help manage the infection and slow or prevent the progression of the disease.

The therapy currently being trialed, which uses CRISPR gene editing to removeHIV viral DNA from infected cells, is a major step towardfinding a therapeutic cure.

We are well-positioned to collect key data that will enable our efforts to translate the success this approach has shown in animal models to human clinical trial participants, Khalili added. We look forward to investigating this hypothesis through the EBT-101 clinical program and are pleased that the EBT-101 Phase 1/2 trial is proceeding as planned.

The first patient to receive a single dose of EBT-101 in the current trial is currently under medical supervision and will soon be assessed to see if there is any viral rebound and whether the single curative treatment worked as planned. This will be a deciding factor in whether or not the patient is able to stop their current antiretroviral therapy in the future.

The official start of the Phase 1/2 clinical trials for EBT-101 brings us one extremely significant step closer to creating a potential cure for HIV/AIDS, said Dr Amy J. Goldberg, Interim Dean of the Katz School of Medicine. This amazing milestone speaks to the exceptional research acumen and scientific knowledge of Drs. Khalili and Burdo and their teams outstanding members of the Temple family.

For further details, you can view the clinical trial information at ClinicalTrials and follow its progress.

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CRISPR-Based HIV Gene Therapy Administered To First Human Patient - IFLScience

CAMBRIDGE, Mass., Sept. 21, 2022 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) today announced that The New England Journal of Medicine(NEJM) has published detailed results from the Phase 3 VALOR study and the combined analysis of VALOR and its open label extension (OLE) study evaluating tofersen for the treatment of superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS). There is currently no treatment targeted for SOD1-ALS.

I see three key take home points from these data.First, tofersen clearly leads to lowering of SOD1 protein, as would be expected.Second there is substantial lowering of neurofilament levels, which I interpret as potentially slowing the underlying disease process. And third, there is a meaningful clinical benefit when looking at the later time points in the open label extension, said Timothy Miller, M.D., Ph.D., principal investigator of VALOR and ALS Center co-Director at Washington University School of Medicine, St. Louis. We are grateful to the dedication from participants, their families, and the sites for taking part in this important study.

Data from the combined analysis were previously presented at the European Network to Cure ALS (ENCALS) annual meeting and included within Biogens New Drug Application for tofersen that was recently accepted for priority review by the U.S. Food and Drug Administration. The application was given a Prescription Drug User Fee Act action date of January 25, 2023.

The ALS community has been actively pursuing new medicines for decades. To have data like these published in NEJM gives us energy and hope. We are now seeing in the data what we suspected about tofersen for a long time that it has the potential to make a clinical difference for people living with SOD1-ALS, said Merit Cudkowicz, M.D., co-principal investigator of the VALOR trial and co-founder of the Northeast ALS Consortium, Director of the Healey & AMG Center for ALS and Chair of Neurology at Massachusetts General Hospital and the Julieanne Dorn Professor of Neurology at Harvard Medical School. The lowering of neurofilament, a marker of axonal injury and neurodegeneration along with the clinical data, highlights the potential of tofersen.

About VALOR and the OLEVALOR was a six-month Phase 3, randomized, double-blind, placebo-controlled study to evaluate the effects of tofersen 100 mg in adults with ALS associated with a SOD1 mutation. In total, 108 participants were randomized in VALOR (n=72 to tofersen 100 mg and n=36 to placebo). Of these participants, 95 enrolled in the ongoing OLE. At the time of the analysis all participants had an opportunity for at least 12 months of follow-up, with a median exposure to tofersen of approximately 20 months (range: 1 34 months).

The primary endpoint of VALOR was change from baseline to week 28 in ALS Functional Rating Scale-Revised (ALSFRS-R) total score. Secondary endpoints included changes in total cerebrospinal fluid SOD1 protein concentration, plasma neurofilament light chain (NfL), slow vital capacity and handheld dynamometry in 16 muscles.

As previously reported in October 2021, VALOR did not meet the primary endpoint. However, trends of reduced disease progression across multiple secondary and exploratory endpoints were observed. The combined VALOR and OLE 12-month data, in which the clinical analyses adjusted for neurofilament levels as a marker of the disease progression rate at baseline, showed sustained reductions in SOD1 protein (a marker of target engagement) and neurofilament (a marker of neurodegeneration) and slowed decline in clinical function, respiratory function, strength, and quality of life with earlier initiation of tofersen.

In the 12-month data, the most common adverse events (AEs) in participants receiving tofersen in VALOR and the OLE study were procedural pain, headache, pain in the arms or legs, falls, and back pain. Most AEs in both VALOR and the OLE were mild to moderate in severity. Serious neurologic events including myelitis, chemical or aseptic meningitis, radiculitis, increased intracranial pressure and papilledema, were reported in 6.7 percent of participants receiving tofersen in VALOR and its OLE.

About TofersenTofersen is an antisense drug being evaluated for the potential treatment of SOD1-ALS. Tofersen binds and degrades SOD1 mRNA to reduce synthesis of SOD1 protein production. In addition to the ongoing open label extension of VALOR, tofersen is being studied in the Phase 3 ATLAS study designed to evaluate whether tofersen can delay clinical onset when initiated in presymptomatic individuals with a SOD1 genetic mutation and biomarker evidence of disease activity. Biogen licensed tofersen from Ionis Pharmaceuticals, Inc. under a collaborative development and license agreement.

About Amyotrophic Lateral Sclerosis and SOD1-ALSAmyotrophic lateral sclerosis (ALS) is a rare, progressive and fatal neurodegenerative disease that results in the loss of motor neurons in the brain and the spinal cord that are responsible for controlling voluntary muscle movement. People with ALS experience muscle weakness and atrophy, causing them to lose independence as they steadily lose the ability to move, speak, eat, and eventually breathe. Average life expectancy for people with ALS is three to five years from time of symptom onset.1

Multiple genes have been implicated in ALS. Genetic testing helps determine if a persons ALS is associated with a genetic mutation, even in individuals without a family history of the disease. Currently, there are no genetically targeted treatment options for ALS. Mutations in the SOD1 gene are responsible for approximately 2 percent of the estimated 168,000 people who have ALS globally (SOD1-ALS).2Life expectancy in SOD1-ALS varies widely with some patients surviving less than a year.3

Biogens Continuous Commitment to ALSFor over a decade, Biogen has been committed to advancing ALS research to provide a deeper understanding of all forms of the disease. The company has continued to invest in and pioneer research despite making the difficult decision to discontinue a late-stage ALS asset in 2013. Biogen has applied important learnings to its portfolio of assets for genetic and other forms of ALS, with the goal of increasing the probability of bringing a potential therapy to patients in need. These applied learnings include evaluating genetically validated targets in defined patient populations, pursuing the most appropriate modality for each target and employing sensitive clinical endpoints. Today, the company has a pipeline of investigational drugs being evaluated in ALS, including tofersen and BIIB105.

About BiogenAs pioneers in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases as well as related therapeutic adjacencies. One of the worlds first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has a leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, and developed the first and only approved treatment to address a defining pathology of Alzheimers disease. Biogen is also commercializing biosimilars and focusing on advancing one of the industrys most diversified pipelines in neuroscience that will transform the standard of care for patients in several areas of high unmet need.

In 2020, Biogen launched a bold 20-year, $250 million initiative to address the deeply interrelated issues of climate, health, and equity. Healthy Climate, Healthy Lives aims to eliminate fossil fuels across the companys operations, build collaborations with renowned institutions to advance the science to improve human health outcomes, and support underserved communities.

We routinely post information that may be important to investors on our website atwww.biogen.com.Follow us on social media-Twitter,LinkedIn,Facebook,YouTube.

Biogen Safe HarborThis news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including statements about results from the Phase 3 VALOR study of tofersen or its OLE; the potential clinical effects of tofersen; the potential benefits, safety and efficacy of tofersen; the clinical development program for tofersen; the potential approval of tofersen; the identification and treatment of ALS; our research and development program for the treatment of ALS; the potential of our commercial business and pipeline programs, including tofersen; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be accompanied by words such as aim, anticipate, believe, could, estimate, expect, forecast, intend, may, plan, potential, possible, will, would and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk and only a small number of research and development programs result in commercialization of a product. Results in early stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements or the scientific data presented.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation, uncertainty of success in the development and potential commercialization of tofersen; the risk that we may not fully enroll our clinical trials or enrollment will take longer than expected; unexpected concerns may arise from additional data, analysis or results obtained during our clinical trials; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of our drug candidates, including tofersen; the occurrence of adverse safety events; the risks of unexpected hurdles, costs or delays; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; and the direct and indirect impacts of the ongoing COVID-19 pandemic on our business, results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this news release.

We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

References:

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The New England Journal of Medicine Publishes Pivotal Tofersen Data that Show Benefits in Rare, Genetic Form of ALS - GlobeNewswire

Mitochondria are structures within the cell that convert energy from food into energy the cell can use. Each cell contains hundreds to thousands of mitochondria. Although most DNA is found inside the cells nucleus, mitochondria also contain a small amount of DNA, known as mitochondrial DNA.

In the early 2000s, researchers realized that short sections of mitochondrial DNA encode small (less than 100 amino acids long), biologically active proteins, now referred to as mitochondrial microproteins. The first mitochondrial microprotein to be discovered was called humanin.

There is growing evidence that humanin and other similar mitochondrial microproteins play a role in several age-related conditions, including Alzheimers disease.

Alzheimers disease is the most common type of dementia, characterized by progressive mental deterioration. According to the CDC, as many as 5.8 million Americans were living with Alzheimers disease in 2020.

The Cohen Laboratory at the University of Southern California (USC), one of the three laboratories that independently discovered humanin in 2003, has discovered a new microprotein connected to the risk of Alzheimers disease.

Their latest research, published in the journal of Molecular Psychiatry, revealed that a mutation in the newly discovered SHMOOSE microprotein is associated with a higher risk for Alzheimers disease across four cohorts. According to the researchers, nearly 1 in 4 individuals with European ancestry have the mutated version of the protein.

Dr. Pinchas Cohen, professor of gerontology, medicine, and biological sciences and senior author of the study, told Medical News Today:

The implications are not immediate, but we believe that [relatively soon], the SHMOOSE SNP [single nucleotide polymorphism] genetic variant that is found in over 20% of Europeans may guide both the classification of individuals that are at risk for Alzheimers that may benefit from certain preventive measures and also could inform the selection of medical interventions that will become available in the near future. A bit further ahead, SHMOOSE [protein] analogues may become available as therapeutics for individuals who carry the SNP and develop dementia, in a precision medicine approach.

Brendan Miller, Ph.D., first author of the study, studied mitochondrial DNA sequences from the Alzheimers Disease Neuroimaging Initiative (ADNI) database, searching for small variations in the genes called single nucleotide polymorphisms or SNPs. He found that a mutation in one particular mitochondrial SNP (rs2853499) was associated with a greater risk of Alzheimers disease and brain atrophy.

Dr. Miller and his colleagues then discovered that the mutated SNP causes a change in a mitochondrial microprotein, which they called SHMOOSE. The researchers used a technique called immunoprecipitation to isolate the SHMOOSE microprotein from the mitochondria of nerve cells.

When they analyzed this sample using mass spectrometry, they detected and identified two unique protein fragments from the SHMOOSE microprotein. The researchers reported that this is the first unique mass spectrometry-based detection of a mitochondrial-encoded microprotein to date.

Having identified a microprotein associated with a higher risk of Alzheimers disease, the researchers followed up on their discovery by carrying out studies in rats and cell culture experiments.

They found that the SHMOOSE microprotein accumulates in the mitochondria of neurons (nerve cells), where it binds to the inner mitochondrial membrane protein mitofilin. The SHMOOSE microprotein appears to act on the brain by influencing mitochondrial gene expression and boosting mitochondrial oxygen consumption. The researchers noted that mutated SHMOOSE microprotein was less effective at boosting oxygen consumption and impacted gene expression differently.

Dysregulated mitochondrial associated brain energetics is one of the multiple pathways thought to be important for Alzheimers disease, Andrew Saykin, PsyD, ABCN, Professor and Director of the Center for Neuroimaging and Indiana Alzheimers Disease Research Center, told MNT.

George Perry, Ph.D., Professor and Semmes Foundation Distinguished University Chair in Neurobiology at the University of Texas at San Antonio, told MNT that this study is very important as it links risk of [Alzheimers disease] to cellular metabolism. There are numerous cell biology and biochemical studies that highlight this [] and finding genetic data further support[s] this view.

Dr. Saykin observed that with further development and validation there could be implications of this and other microproteins for early detection, longitudinal monitoring, and potentially for therapeutic targeting.

MNT also discussed the studys findings with Tal Nuriel, Ph.D., Assistant Professor of Pathology and Cell Biology at Columbia University Irving Medical Center. Dr. Nuriel told MNT that most Alzheimers disease-related gene mutations discovered in the past are either very rare variants or common variants that confer a very small risk.

He said the mutation, or variant, in the SHMOOSE microprotein appears to confer a moderate risk for Alzheimers disease and is relatively common in the population and [this] alone makes it interesting.

Dr. Nuriel added that the fact that this is a microprotein that can theoretically be administered as a therapeutic agent is valuable. He cautioned that there will be a very long road ahead before any therapy derived from this microprotein could become a reality. Importantly, its unclear whether this SHMOOSE microprotein would enter the brain if given subcutaneously or intravenously. And if it doesnt enter the brain, this would greatly limit its ability to be used therapeutically.

When asked about the next step in the research following this discovery, Dr. Cohen told MNT, Our immediate plan is to treat mice that have been engineered to develop Alzheimers disease with SHMOOSE over several months and assess the improvement in their symptoms and performance. We will also work on developing longer acting analogues of the pep[t]ide.

The researchers noted in the study that SHMOOSE is yet another microprotein of a growing number that modify mitochondrial biology. According to a recent review, thousands of DNA sequences with microprotein-coding potential are currently unverified or functionally uncharacterized.

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Alzheimer's disease risk linked to newly discovered protein mutation - Medical News Today

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