USP30

Review article in high impact journal outlines the evidence that neurodegenerative diseases –including Parkinson's, Alzheimer's, ALS and Huntington's – can be addressed by boosting mitophagy, the quality control system cells use to remove dysfunctional mitochondria Strong evidence has emerged that deficient mitophagy is an underlying cause of neurodegenerative disease Momentum is building, with the first selective mitophagy enhancers aimed at modifying the course of neurodegenerative diseases entering clinical trials in the last 12 months CAMBRIDGE, England, Jan. 15, 2025 /PRNewswire/ -- Mission Therapeutics ("Mission"), a clinical-stage biotech company developing first-in-class therapeutics targeting mitophagy, today announces the publication of a review article titled Targeting mitophagy in neurodegenerative diseases in the journal Nature Reviews Drug Discovery. The peer-reviewed article can be viewed here. It outlines the progress scientists have made in identifying that mitochondrial dysfunction is a hallmark of neurodegenerative disease; how their understanding of the molecular pathways that underpin the mitophagy process has advanced; and the subsequent development of two molecular approaches – USP30 inhibition and PINK1 activation – which are now being tested in early-stage clinical trials. Dr Paul Thompson, Chief Scientific Officer at Mission Therapeutics, said: "Fresh scientific approaches are needed if we as a society are to address the growing burden of neurodegenerative diseases, which are becoming ever more common as populations age. This timely review outlines the significant potential that enhancing mitophagy has in tackling a wide range of neurodegenerative diseases including Parkinson's, Alzheimer's, amyotrophic lateral sclerosis (ALS) and Huntington's." Dr Laura Parton, Senior Director at Mission Therapeutics, said: "We now have a deep understanding of how the build-up of dysfunctional mitochondria can contribute to neurodegenerative diseases – and how we can go about addressing this problem with selective mitophagy enhancers, particularly those focussing on the USP30/PINK1/Parkin mitophagy pathway. After more than 30 years of research, the area is now coming to fruition, with three such drugs entering clinical trials in the last 12 months." The review was written by a team of renowned mitophagy experts from across industry and academia, including Mission scientists Dr Paul Thompson and Dr Laura Parton; Professor Miratul Muqit and Odetta Antico of Dundee University; and Dr Nicholas T. Hertz, co-founder of Mitokinin LLC. Mission Therapeutics is a global leader in discovering and developing innovative therapeutics that promote mitophagy, the quality control process cells use to remove dysfunctional mitochondria, thereby safeguarding their health and function. Effective mitophagy is particularly important for the ongoing health of neurons as, unlike most cells, they do not self-renew throughout an individual's lifetime. About Mission Therapeutics Mission Therapeutics is a world leader in discovering and developing novel therapeutics which promote the removal of dysfunctional mitochondria, promoting cell health and function. Mitochondria are energy producing organelles which require lifetime quality control through a ubiquitin-mediated clearance mechanism known as mitophagy. In certain situations, such as cellular stress, cell injury, and/or defects of the mitophagy process, the mitochondria can become dysfunctional and damaging to the cell, leading to reduced energy production, oxidative stress, inflammation and potentially cell death. Dysfunctional mitochondria are significant drivers of disease pathophysiology in acute kidney injury (AKI), Parkinson's disease (PD), heart failure, Duchenne's Muscular Dystrophy, IPF, mitochondrial diseases and Alzheimer's. USP30 is a deubiquitylating enzyme that constantly removes ubiquitin from mitochondria, providing a potential brake on clearance of dysfunctional mitochondria. Mission is currently developing two small molecule drugs, MTX652 (peripheral) and MTX325 (targeting the CNS) which, through inhibition of the mitochondrial DUB enzyme USP30, will promote clearance of dysfunctional mitochondria – consequently improving overall cellular health. Mission's USP30 inhibitors MTX652 and MTX325 could potentially be used to treat any disease or condition driven by mitochondrial dysfunction. Mission is backed by blue chip investors including Pfizer Venture Investments, Sofinnova Partners, Roche Venture Fund, SR One, IP Group and Rosetta Capital. SOURCE Mission Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

DOYLESTOWN, Pa., Sept. 4, 2024 /PRNewswire/ -- Mid-Atlantic BioTherapeutics (MABT) and Accelero Biostructures (Accelero) are pleased to announce a research collaboration to identify novel USP30 inhibitors targeting neurological disorders and other important medical indications. Accelero will use its novel and proprietary ABS-OneStepSM platform based on high-throughput protein X-ray crystallography-based fragment screening as the hit generation engine for drug discovery coupled with machine learning/artificial intelligence (ML/AI)-based computational chemistry. MABT will perform all preclinical testing and will also assume advanced development of the resulting compounds. MABT CEO David Horn, M.D. commented that "USP30 is an exciting, emerging target that, once effectively modulated, may have a meaningful clinical impact on several neurological disorders like Alzheimer's and Parkinson's Diseases, as well as a range of other medical targets. We are looking forward to working with the Accelero team to rapidly discover novel compounds using their powerful ABS-OneStep platform." "Our partnership with MABT further validates the promise of our ABS-OneStep platform to discover novel chemical matter that targets promising proteins like USP30," said Debanu Das, Ph.D., Accelero Co-Founder and CEO. "The ABS-OneStep platform has been successfully utilized on multiple diverse protein targets, and we are confident the platform will identify new molecules against USP30." About USP30 USP30 is a deubiquitinating enzyme (DUB) that plays a crucial role in regulating cellular processes, particularly those related to mitochondria. USP30 regulates mitophagy, a process where damaged mitochondria are selectively removed from cells. This process is essential for maintaining cellular health and preventing oxidative stress. Mounting evidence has shown that USP30 may play an important role in various neurological diseases. About MABT Mid-Atlantic BioTherapeutics (MABT) was founded in 2011 with the mission of combating some of the world's worst diseases like rabies encephalitis, Alzheimer's and Parkinson's Disease and other severe neurological disorders. We have received Orphan Drug Designation for our lead rabies program and are developing novel treatments for a range of other neurological disorders. Fundamentally, we are opportunistic in our evaluation of new strategies and approaches that address a significant medical need and commercial market. About Accelero Accelero Biostructures was founded in 2015 to capitalize on over 20 years of structural genomics and structural biology expertise developing and deploying high-throughput protein X-ray crystallography. ABS-ServicesSM provides a unified pipeline of protein X-ray crystallography solutions aimed at the pharmaceutical and biotechnology industries to support structure-based drug discovery and protein engineering. ABS-OneStepSM is the next-generation platform for hit generation in early drug discovery to develop novel therapeutics using a fragment-based drug discovery (FBDD) approach. Fragment library screening with ABS-OneStepSM resolves key bottlenecks in conventional FBDD approaches. ABS-OneStepSM provides an extremely sensitive, efficient, experimental, single-step approach for determining fragment hits and their 3D structures using high-throughput protein X-ray crystallography. Disclaimer Development of the ABS-OneStepSM platform for high-throughput protein X-ray crystallography-based fragment screening has been supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under Award Number R43TR001736, and the National Institute of General Medical Sciences of the NIH under Award Number R44GM132796, to Accelero Biostructures Inc. SOURCE Mid-Atlantic BioTherapeutics, Inc.

Investment will support investigation of Mission's small molecule drug MTX325 in patients with early-stage Parkinson's disease Marks latest step in Mission's relationship with The Michael J. Fox Foundation (MJFF), after MJFF awarded Mission preclinical research grants in 2017 and 2021, and first with Parkinson's UK Comes as promising early data from healthy volunteers show MTX325 has a good safety profile, pharmacokinetics and CNS penetration CAMBRIDGE, England, July 2, 2024 /PRNewswire/ -- Mission Therapeutics ("Mission" or the "Company"), a clinical-stage biotech developing first-in-class therapeutics targeting mitophagy, has been awarded $5.2 million from The Michael J. Fox Foundation for Parkinson's Research (MJFF) and Parkinson's UK. The funding will help advance Mission's potential disease-modifying treatment for Parkinson's, MTX325. MTX325 is a potent, selective, small molecule brain-penetrant USP30 inhibitor, which is designed to protect dopamine-producing neurons by improving mitochondrial quality and function. The funding will support a 28-day dosing of MTX325 in patients with early-stage Parkinson's disease (PD), as part of Mission's ongoing MTX325 Phase I program. Patient dosing is expected to start early in 2025. The aims are to understand MTX325's safety, tolerability, pharmacokinetic profile and CNS penetration in PD patients, as well as observing effects on relevant mechanisms and disease biology biomarkers. Mission started its multi-part, adaptive Phase I first-in-human clinical trial of MTX325 in March, beginning with a single ascending dose stage in healthy volunteers. Initial investigations of MTX325's CNS penetration ability in these healthy volunteers have yielded positive results. The multiple ascending dose stage of the study was initiated last month (June). Anker Lundemose, Chief Executive Officer, Mission Therapeutics, said: "This significant grant, from two of the world's leading Parkinson's disease organisations, underlines the huge potential of MTX325 as a disease-modifying treatment for this terrible neurodegenerative illness. It also represents a major endorsement of our mitophagy strategy in human diseases including PD." Dr Paul Thompson, Chief Scientific Officer, Mission Therapeutics, said: "We have already made excellent progress in healthy volunteers with preliminary data from the ongoing clinical trial showing that MTX325 has a good single dose safety profile, pharmacokinetics and CNS penetration. We look forward to starting the PD patient part of the trial in the new year, which this generous funding from MJFF and Parkinson's UK is helping to support." Katharina Klapper, director of clinical research at MJJF, said: "Mission Therapeutics has made great advances in the understanding of how mitochondrial health can play a pivotal role in the development of Parkinson's disease in recent years. We look forward to seeing the results of the MTX325 trial." Dr Arthur Roach, Director of the Parkinson's Virtual Biotech at Parkinson's UK, said: "We are delighted to be working with Mission Therapeutics to help fund this vital, UK-based clinical trial. Disease-modifying treatments are one of the great hopes of people with Parkinson's. We now know that mitochondria play a crucial role in the development of Parkinson's, so addressing mitochondrial problems could have far-reaching benefits for those living with the condition." Parkinson's is a neurodegenerative disease which affects around 10 million people globally. It is characterised by low levels of the neurotransmitter dopamine and there are currently no approved disease-modifying treatments for the condition. MTX325 protects dopamine-producing neurons by enhancing a cellular quality control process called mitophagy, in which faulty mitochondria are tagged and then removed. MTX325 does this by inhibiting USP30, a deubiquitylating enzyme (DUB) which impedes normal mitophagy. Last December scientists at Cambridge University, Harvard University and Mission Therapeutics published a key academic paper outlining preclinical research on USP30 and MTX325 in the journal Nature Communications. The paper detailed knockout mouse model data which, the authors said, provided strong experimental evidence supporting the thesis that MTX325 can modify the course of PD by targeting USP30. A growing body of scientific evidence has linked a build-up of dysfunctional mitochondria in cells to a range of diseases including Parkinson's, kidney disease, heart failure, idiopathic pulmonary fibrosis (IPF) and Duchenne's muscular dystrophy (DMD). About Mission Therapeutics Mission Therapeutics is a world leader in discovering and developing novel therapeutics which promote the removal of dysfunctional mitochondria, promoting cell health and function. Mitochondria are energy producing organelles which require lifetime quality control through a ubiquitin-mediated clearance mechanism known as mitophagy. In certain situations, such as cellular stress, cell injury, and/or defects of the mitophagy process, the mitochondria can become dysfunctional and damaging to the cell, leading to reduced energy production, oxidative stress, inflammation and potentially cell death. Dysfunctional mitochondria are significant drivers of disease pathophysiology in acute kidney injury (AKI), Parkinson's disease (PD), heart failure, Duchenne's Muscular Dystrophy, IPF, mitochondrial diseases and Alzheimer's. USP30 is a deubiquitylating enzyme that constantly removes ubiquitin from mitochondria, providing a potential brake on clearance of dysfunctional mitochondria. Mission is currently developing two small molecule drugs, MTX652 (peripheral) and MTX325 (targeting the CNS) which, through inhibition of the mitochondrial DUB enzyme USP30, will promote clearance of dysfunctional mitochondria – consequently improving overall cellular health. Mission's USP30 inhibitors MTX652 and MTX325 could potentially be used to treat any disease or condition driven by mitochondrial dysfunction. Mission is backed by blue chip investors including Pfizer Venture Investments, Sofinnova Partners, Roche Venture Fund, SR One, IP Group and Rosetta Capital. About MTX325 and USP30 MTX325 is a potent selective central nervous system-penetrant compound designed to improve mitochondrial quality and function by enhancing mitophagy. MTX325 inhibits USP30, a deubiquitylating enzyme localised to mitochondria which is a negative regulator of mitophagy. Data from an in vivo model of Parkinson's, where USP30 was deleted through gene knockout, validate USP30 as a potential target in PD. Researchers found MTX325 produced a similar effect to gene knockout of USP30 in the same PD mouse model, further validating the approach of USP30 inhibition in PD. See the paper in Nature Communications here: About Parkinson's UK and the Parkinson's Virtual Biotech We are Parkinson's UK. Here for everyone affected by the condition. Funding research into the most promising treatments, taking us closer to a cure every day. Fighting for fair treatment and better services. In 2017, we founded the Parkinson's Virtual Biotech. A groundbreaking global movement to deliver life-changing new treatments in years not decades. It uses cutting edge biological and chemical research to come up with new treatments. Driven by people with Parkinson's, not profit, it adapts successful methods from the biotech and business worlds to deliver new treatments faster. The Parkinson's Virtual Biotech is now an international programme in partnership with the Parkinson's Foundation. We believe we'll get a cure faster by collaborating, not competing. The innovative approach is working. The next treatment is closer than ever. Further information, advice and support is available on our website, SOURCE Mission Therapeutics