ReviR Therapeutics, a biotech company focused on developing innovative treatments for neurogenetic diseases, announced  that it has been awarded a $4.6M grant from the California Institute for Regenerative Medicine (CIRM), and has recently reached a key program milestone, having identified a lead compound that meets key development criteria. This funding will further support the advancement of ReviR Therapeutics' HTT-PMS1 genetic medicine program, whereby a small molecule selectively reduces the mRNA of two genes implicated in both the cause and progression of Huntington's disease (HD). ReviR's novel VoyageR technology platform and scientific approach signify a potential paradigm shift in the treatment of neurodegenerative diseases, providing a more accessible treatment option. The development of this therapeutic asset will pave the way for similar therapies targeting other genetic disorders.

The CIRM grant is awarded through a competitive peer-review process, highlighting the strength of ReviR Therapeutics' research and its potential impact on Huntington's disease. The funding will support the development of a transformative therapy that employs a dual-mechanism approach to combat HD by targeting both mutant huntingtin protein (mHTT) and the protein mismatch repair enzyme PMS1. By selectively degrading the mRNA of two of the most critical drivers of Huntington's pathology, the therapy not only reduces the toxic protein aggregates associated with the disease but also curtails the somatic CAG repeat expansion in HD patients, potentially altering the long-term course of the disease. The CIRM grant will enable ReviR Therapeutics to further develop their preclinical candidate through rigorous preclinical studies and into clinical trials, with an initial goal to ensure that the therapy is both effective in reducing disease progression and amenable to routine clinical use.

Huntington's disease is a neurodegenerative disorder caused by an abnormal expansion of CAG trinucleotide repeats in the huntingtin (HTT) gene. Individuals with HD have more than 36 CAG repeats in the HTT gene, resulting in the production of mutant huntingtin protein, which leads to the synthesis of mutant huntingtin protein (mHTT) with an expanded polyglutamine tract. This aberrant protein undergoes misfolding and aggregation within neurons, disrupting various cellular functions. Recent research has revealed^[1] that while the CAG length is fixed at birth, the repeats can further expand over time within certain brain cells. Once these expansions exceed a critical threshold (~150 CAG repeats), they cause neuronal death, leading to the development of HD symptoms. 

Paul R. August, PhD, Chief Scientific Officer at ReviR Therapeutics, commented on the grant's significance: "This CIRM grant is a cornerstone for our targeted approach in treating Huntington's disease. By leveraging our proprietary RNA-targeting technology and our platform VoyageR, this molecule is poised to revolutionize how we treat HD - offering not just symptomatic relief but a potential disease-modifying therapy, filling an unmet medical need. The ability to deliver this therapy orally would mark a significant breakthrough, enhancing HD patient compliance and quality of life."

"We are grateful to CIRM for validating our scientific approach and funding the development of this life-changing therapy for HD patients and other neurodegenerative diseases," said Peng Yue, PhD, co-founder and CEO of ReviR Therapeutics. "This grant will help us advance our dual HTT-PMS1 program toward clinical trials, potentially transforming the treatment landscape for Huntington's disease patients."