14 Dec Genetic Test Can Predict Predisposition to Drug-Induced Brain Infection PML
MedicalResearch.com Interview with:
Dr. Eli Hatchwell, MA MB BChir (Cantab) DPhil (Oxon) BA (OU)
Chief Scientific Officer
Population Bio UK, Inc.
Begbroke Science Park Begbroke Hill
MedicalResearch.com: What is the background for this study?
Response: Progressive Multifocal Leukoencephalopathy (PML) is a devastating condition that is associated with a number of clinical situations, including treatment with a variety of drugs. Of these, the best known is natalizumab (Tysabri), which is a very successful drug in the treatment of MS (multiple sclerosis). Only a small proportion of patients treated with natalizumab develop PML and this has always been a mystery. The study was based on a hypothesis that some individuals have an underlying susceptibility to developing PML, based on the presence of variants in genes that are important in the immune system. The study identified several of these variants.
MedicalResearch.com: Where is the polyomavirus 2 found?
Response: The polyoma 2 virus (aka JCV) has an estimated worldwide prevalence of 40–70%. More recent studies in Asian populations showed even higher rates, ranging from 70- 80%. In the body, the virus is found particularly in the kidneys in a dormant state but in PML, it is found at high levels in the brain.
MedicalResearch.com: What are the main findings?
Response: The study describes four variants that may account for 11% of drug-induced PML. Individuals with one or more of these variants are predicted to be at significantly higher risk of Progressive Multifocal Leukoencephalopathy compared to those who test negative. These variants are in genes with known roles in not only the immune system but also viral defense.
MedicalResearch.com: What should readers take away from your report?
Response: For the first time, a specific test is available that predicts an individual’s risk of Progressive Multifocal Leukoencephalopathy. The test should be implemented clinically to inform physicians and their patients of their individual risk for PML. Those who test positive are advised to avoid drugs with especially high risks of PML (in particular, Tysabri).
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: The insights gleaned from this study pave the way for future studies to expand the number of genes/variants that are implicated in Progressive Multifocal Leukoencephalopathy risk. Further, some of the insights may suggest interventions that will help treat PML. We view our study as a demonstration of the power of precision medicine in relation to drug adverse events.
Disclosures: I am Chief Scientific Officer and co-founder of Population Bio.
Progressive Multifocal Leukoencephalopathy Genetic Risk Variants for Pharmacovigilance Immunosuppressant Therapies
Link to article: https://www.frontiersin.org/articles/10.3389/fneur.2022.1016377/full
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