Vanda Pharmaceuticals recently announced a significant achievement: the FDA's approval of their Investigational New Drug (IND) application for evaluating VCA-894A in treating patients with Charcot-Marie-Tooth disease, axonal, type 2S (CMT2S). This rare subtype of Charcot-Marie-Tooth disease (CMT) is caused by cryptic splice site variants within the IGHMBP2 gene and currently lacks available treatment options.
CMT2S is characterized by slowly progressive distal muscle weakness and atrophy, typically appearing in a child's first decade of life, leading to decreased reflexes and sensory impairment. The overall prevalence of CMT is estimated at 1 in 2,500 individuals, with the CMT2S variant being even rarer at less than 1 in 1,000,000 worldwide.
This approval marks a significant step towards personalized medicine, offering hope for patients with CMT2S and genetic mutations. VCA-894A, a novel antisense oligonucleotide (ASO), targets a cryptic splice site variant within the IGHMBP2 gene, which is pivotal in the manifestation of CMT2S. ASOs, capable of modulating gene expression, hold promise for treating rare diseases by addressing specific genetic variants.
VCA-894A, a 2'-O-methoxyethyl (MOE) phosphorothioate oligonucleotide sodium salt, demonstrates targeted action against the cryptic splice site variant within IGHMBP2 associated with CMT2S. ASOs, with successful delivery to the central nervous system in various programs, offer potential in addressing neurodegenerative and neuromuscular disorders beyond CMT2S. This approval represents a significant advancement in the pursuit of personalized treatments tailored to genetic variants, particularly for rare diseases like CMT2S.