A new drug candidate designed to slow the progression of prion disease is entering a phase 1 clinical trial, which will evaluate the potential medicine for safety and tolerability. Prion diseases are a class of neurodegenerative disorders caused by the accumulation of misfolded prion protein (PrP) in the brain. There are currently no cures, and the disease is fatal within months or years after symptoms begin.
The new drug candidate, developed by Broad Institute and University of Massachusetts Chan Medical School scientists, is a small interfering RNA (siRNA) that binds and snips RNA molecules encoding the prion protein, reducing the amount of the disease-causing protein in the brain. Previous research in animals has shown that lowering prion protein levels can delay onset and slow down the disease. The trial, called PrP-targeting siRNA Safety & Mechanism Study (PRiSM), is enrolling patients exhibiting symptoms of the disease.
The drug candidate is a divalent siRNA: two identical siRNAs that are linked together and designed to distribute more broadly in the brain than single siRNAs. The divalent siRNA was developed at the UMass Chan Medical School by Anastasia Khvorova and her lab. Khvorova, Minikel, and Sonia Vallabh, codirector of Broad’s Prion Therapeutic Science program, have been working together since 2019 on developing an siRNA-based drug to target prion protein mRNA. Vallabh and Minikel, who are wife and husband, have dedicated their lives to creating a cure or treatment for prion disease, after learning in 2011 that Vallabh has the genetic mutation that causes the disease.
In March 2025, the U.S. Food and Drug Administration (FDA) cleared the team’s Investigational New Drug (IND) application to start a clinical trial on this drug candidate — a document that is usually kept private by drug companies. However, Minikel and Vallabh published their IND filing publicly, and have committed to sharing new insights openly. This green light from the FDA — a significant step in the drug development process — follows promising animal data from the Minikel/Vallabh lab. The scientists showed that a divalent siRNA lowered prion protein in mice by 49 percent and resulted in a 64 percent increase in survival time with a single dose after symptom onset. The study is published in Nucleic Acids Research. The clinical trial is being supported by Neuro NEXT, or Network for Excellence in Neuroscience Clinical Trials, a program of the National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health. Neuro NEXT provides both funding as well as infrastructure to run the trial, including trial sites, a clinical coordinating center housed at Mass General Hospital’s Neurology Department, and a data and statistics center at the University of Iowa.
Source: Hacker News · Summarized by HeadlinesBriefing