PINK1

The new research reveals how a protein in brain cells may drive Parkinson's onset -- and offers a possible explanation for why Parkinson's is much more common in men. Scientists at La Jolla Institute for Immunology (LJI) have found a potential new target for treating Parkinson's disease. Their new research reveals how a protein in brain cells may drive Parkinson's onset -- and offers a possible explanation for why Parkinson's is much more common in men. In recent years, LJI scientists have found increasing evidence that autoimmunity plays a role in the onset of Parkinson's disease. Their recent study in The Journal of Clinical Investigation shows that PINK1 appears to mark some brain cells for immune cell attack. "This research allows us to better understand the role of the immune system in Parkinson's disease," says LJI Professor Alessandro Sette, Dr.Biol.Sci., senior author of the recent study. PINK1 means no harm. The protein actually helps brain cells regulate their mitochondria -- the cellular structures that provide energy for a cell. The researchers found that some people with Parkinson's disease have T cells that mistakenly see PINK1 as a red flag. These T cells may target brain cells that express PINK1, contributing to inflammation and brain cell death. The new research may help explain why Parkinson's disease is around twice as common in men versus women. The LJI team found that men with Parkinson's disease had a 6-fold increase in PINK1-specific T cells, compared with healthy male study participants. Women with Parkinson's disease showed only a 0.7-fold increase in PINK1-specific T cells, compared with healthy female study participants. "The sex-based differences in T cell responses were very, very striking," says Sette. "This immune response may be a component of why we see a sex difference in Parkinson's disease." These PINK1-targeting T cells may also prove valuable as a biomarker of Parkinson's disease, allowing for earlier diagnosis in patients at-risk of developing the neurodegenerative disease, says Cecilia Lindstam Arlehamn, P.h.D., who co-led the research at LJI. Studying T cell responses to PINK1 may also guide the development of new Parkinson's disease therapeutics. "We could potentially develop therapies to block these T cells, now that we know why the cells are targeting in the brain," says Lindstam Arlehamn. PINK1 is not the only important T cell target, or "antigen," in patients with Parkinson's disease. Previous research led by Sette and Lindestam Arlehamn showed that many Parkinson's disease patients have T cells that target a protein called alpha-synuclein. This T cell response was linked to inflammation in the brain and the onset of Parkinson's disease. But not all Parkinson's patients show this T cell response to alpha-synuclein, so LJI researchers expanded their hunt for additional antigens that might trigger harmful autoreactive T cell responses in people with Parkinson's disease. The new research suggests PINK1 is one such antigen, but the researchers aren't stopping there. Sette says scientists are just starting to get a full picture of how Parkinson's begins. "We need to expand to perform more global analysis of the disease progression and sex differences -- considering all the different antigens, disease severities, and time since disease onset," says Sette.

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

Initial data from largest international Parkinson’s disease patient cohort shows approximately 90% of these genetically confirmed patients had variants in the LRRK2 or GBA1 genes, making these individuals potential candidates to be included in gene-targeted trialsThe Rostock International Parkinson's Disease (ROPAD) Study aims to characterize the genetics of Parkinson’s disease (PD) to establish a better understanding of disease progression, diagnosis, and treatment for patients CAMBRIDGE, Mass. and ROSTOCK, Germany and BERLIN, Aug. 01, 2024 (GLOBE NEWSWIRE) -- Centogene N.V. (Nasdaq: CNTG), the essential life science partner for data-driven answers in rare and neurodegenerative diseases, today announced data from the Company’s Rostock International Parkinson's Disease (ROPAD) Study revealing the genetic factors and prevalence of Parkinson’s disease (PD). The findings from this landmark study indicate that approximately 15% of PD-related cases are tied to genetic variants, with the majority being linked to LRRK2 and GBA1. The data was published in Brain in a paper titled, “Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease study.” “Over the past five years, CENTOGENE and our more than 100 study sites around the world have worked together to diagnose Parkinson’s patients and accelerate treatment options,” said Prof. Peter Bauer, Chief Medical and Genomic Officer at CENTOGENE. “Our collaborative work clearly shows how significant of a role genetics plays in Parkinson’s disease and underscores the need to integrate genetic testing in routine care of these patients. This will not only enable access to potentially available treatments, but will de-risk and accelerate the development of gene-specific therapies – driving the future of Parkinson’s disease patient care.” The research investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap from over 12,500 patients from 16 countries who have been enrolled in CENTOGENE’s ROPAD Study. In more than 1,800 participants, a PD-relevant genetic test (PDGT) provided a positive result. This included variants linked to the LRRK2 and GBA1 genes, as well as PRKN, SNCA, and PINK1, or a combination of genetic findings in multiple genes. In the emerging era of gene-targeted PD clinical trials, the Company’s findings that approximately 15% of patients harbor potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. By capturing such genetic data, this also allows for differential genetic counselling across the spectrum of different ages at onset and family histories. The Company recently launched a ROPAD Consortium to continue driving PD research and treatment through collaborative efforts. The ROPAD Consortium will build on the vast network of neurologists, existing partnerships with non-profit organizations, and the largest genetic testing program for PD patients worldwide to streamline access to critical data, drive impactful research, and improve the potential for advancing treatment options. To find out more, email: contact.pharma@centogene.com About ROPAD The Rostock International Parkinson's Disease (ROPAD) Study is a global epidemiological study focusing on the role of genetics in Parkinson’s disease (PD). The major goal of the study is to characterize the genetics of PD to establish a better understanding of the disease etiology, diagnosis, and severity. CENTOGENE utilizes CentoCard®, the Company’s proprietary, CE-marked Dried Blood Spot (DBS) collection kit in combination with state-of-the-art sequencing technologies to screen for mutations in LRRK2 and other PD-associated genes. To date, over 18,000 participants from around the world have been tested over a five-year period. About CENTOGENE CENTOGENE’s mission is to provide data-driven, life-changing answers to patients, physicians, and pharma companies for rare and neurodegenerative diseases. We integrate multiomic technologies with the CENTOGENE Biodatabank – providing dimensional analysis to guide the next generation of precision medicine. Our unique approach enables rapid and reliable diagnosis for patients, supports a more precise physician understanding of disease states, and accelerates and de-risks targeted pharma drug discovery, development, and commercialization. Since our founding in 2006, CENTOGENE has been offering rapid and reliable diagnosis – building a network of approximately 30,000 active physicians. Our ISO, CAP, and CLIA certified multiomic reference laboratories in Germany utilize Phenomic, Genomic, Transcriptomic, Epigenomic, Proteomic, and Metabolomic datasets. This data is captured in our CENTOGENE Biodatabank, with over 850,000 patients represented from over 120 highly diverse countries, over 70% of whom are of non-European descent. To date, the CENTOGENE Biodatabank has contributed to generating novel insights for more than 300 peer-reviewed publications. By translating our data and expertise into tangible insights, we have supported over 50 collaborations with pharma partners. Together, we accelerate and de-risk drug discovery, development, and commercialization in target and drug screening, clinical development, market access and expansion, as well as offering CENTOGENE Biodata Licenses and Insight Reports to enable a world healed of all rare and neurodegenerative diseases. To discover more about our products, pipeline, and patient-driven purpose, visit www.centogene.com and follow us on LinkedIn. Contacts:Melissa HallCENTOGENECorporate Communications Press@centogene.com Lennart StreibelCENTOGENEInvestor Relations IR@centogene.com