RAB32

Rostock International Parkinson's Disease (ROPAD) Study demonstrates a significant link between the RAB32 gene variant and Parkinson's disease, further supporting recent findingsData from over subcohort of 3,350 patients shows that the RAB32 mutation is over 100 times more prevalent in Parkinson's patients than in the general population CAMBRIDGE, Mass. and ROSTOCK, Germany and BERLIN, Sept. 25, 2024 (GLOBE NEWSWIRE) -- Centogene N.V., 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), further supporting the association of a RAB32 gene mutation with Parkinson's disease (PD). The study, published in The Lancet Neurology, builds on research from Emil K. Gustavsson and colleagues, who previously identified the RAB32 c.213C>G (p.Ser71Arg; dbSNP rs200251693) variant as a novel monogenic cause of PD. In the ROPAD Study, Whole Genome Sequencing (WGS) data from 3,354 PD patients revealed that nine patients from Germany, Italy, Spain, and Türkiye carried the RAB32 c.213C>G mutation. This proportion of variant-positives — 0.3% of the cohort — is significantly higher than the 0.002% found in general population databases such as the Genome Aggregation Database. "Over the past five years, CENTOGENE, alongside over 100 study sites globally, have partnered to diagnose Parkinson's patients and advance treatment options," said Prof. Peter Bauer, Chief Medical and Genomic Officer at CENTOGENE. “Building on the initial insights from Gustavsson and colleagues, we were able to dive into our ROPAD cohort to develop a deeper understanding of RAB32 c.213C>G as a cause for Parkinson’s and shed light on the way to a potential cure. These types of game-changing insights are what we are striving for every day.” Key Findings: Nine ROPAD participants (0.3% of the cohort) were heterozygous for the RAB32 c.213C>G mutation, supporting the mutation's causal role in Parkinson’s diseaseAge at onset in mutation-positives and mutation-negatives did not differ, while gender proportions and certain clinical characteristics didThe RAB32 Ser71Arg-associated haplotype was as in the Gustavsson et al. study, supportive of a single founder mutational event These findings underscore the importance of RAB32 as an important cause of Parkinson's disease. “Our collaborative efforts have highlighted the critical impact of genetics on Parkinson’s disease and emphasize the importance of incorporating genetic testing into the standard care of these patients,” said Christian Beetz, Senior Director Genomic Innovation at CENTOGENE. “This will not only open doors to potential treatments, but also expedite and mitigate risks in the development of gene-targeted therapies – shaping the future of Parkinson’s care.” “The study results are a perfect reflection of the significance of data and collaboration in establishing a deep disease understanding,” adds Krishna Kumar Kandaswamy, Vice President of R&D Bioinformatics at CENTOGENE. “By assembling the world's largest genetic Parkinson’s disease cohort, we have gained unprecedented insights that will fuel further research, clinical development, and ultimately, improved patient outcomes.” 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 all known 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

Research finds an overlap in the mechanism of hair color determination and bone resorption, which is associated with bone related diseases like osteoporosis. The findings revealed that proteins named Rab32 and Rab38 play pivotal roles in bone resorption in osteoclast, cell specialized in the process. These proteins are also crucial for pigmentation of hair and skins. Bone is maintained via delicate balance between formation and resorption, and its imbalance leads to bone related diseases like osteoporosis rheumatism and periodontitis. In studies published in scientific journals J Biol Chem and Cell Struct Funct, researchers led by Osaka University revealed proteins named Rab32 and Rab38 play pivotal roles in bone resorption in osteoclast, cell specialized in the process. These proteins are also crucial for pigmentation of hair and skins. Bone is resorbed by specialized cell called osteoclast, and several substances are secreted out to the pits where osteoclast attaches to bones and resorption occurs, like acids (H+) and degrading enzymes (TRAP, CatK). Rab is a group of small proteins that regulate the logistics between diverse compartments inside the cells called organelle. Over 50 Rab proteins are known in mammalian cells including human and mouse, and they are thought to be specifically involved in the traffic between each specific organelle, thereby reliable logistics between them are guaranteed. "Despite osteoclast should employ Rab dependent traffic, which Rabs are involved had been scarcely understood" says lead author of the first paper, Kazuya Noda. "To better understand the molecular mechanisms of osteoclast function, we first screened Rab proteins especially induced during osteoclast formation in mouse." Rab38 was found to be elevated during differentiation into osteoclast. Importantly, Rab38 has closely resembled partner Rab32, and both of them are known to be important for determination of hair color, by regulating the logistics to melanosome, an organelle specialized for color pigmentation in skin and hair forming cells. In the second paper, lead author Kanako Tokuda constructed mouse deleted of both Rab32 and Rab38 from whole body, namely double knock out mouse. As expected, double knock out mouse shows beige-like hair color and red eyes, while wild type mouse has black hair and eyes. Interestingly, double knock out mouse shows increased bone density and as the age progress, the spine becomes more bent especially in male mouse. "We also showed bone resorption by osteoclast is defected in doble knock mouse" says co-senior author of the second paper, Shiou-ling Lu. "We revealed Rab32 and Rab38 engaged organelle, LRO, is important for bone resorption by osteoclast." Significantly, bone related diseases like osteoporosis, rheumatism and periodontitis are associated hyper activation of bone resorption by osteoclast. "Therefore, understanding the underlying mechanism of bone resorption facilitated by Rab32 and Rab38 will provide us useful information regarding potential treatment target for these diseases" says senior author of the two papers, Takeshi NODA.