Potential Treatment: CMT2S Caused By IGHMBP2 Cryptic Splice Site Variant With ASO Based Therapeutic

Monday, October 2nd at 12:30 pm US EDT.

VCA-894A is a novel antisense oligonucleotide (ASO) with a mechanism of action that specifically targets a cryptic splice site variant within immunoglobulin mu-binding protein 2 (IGHMBP2). Mutations within IGHMBP2 play a pivotal role in the manifestation of CMT2S, likely due to alpha-motor neuron loss, and consequently peripheral nervous system deterioration. ASOs have the capacity to modulate gene expression, allowing for the personalized treatment of rare diseases. CMT2S is a rare subtype of Charcot-Marie-Tooth disease (CMT), an inherited peripheral neuropathy for which there is no available treatment. The prevalence of CMT2S is estimated to be less than 1 in 1,000,000 worldwide. Onset of CMT2S begins in early childhood. CMT2S is characterized by slowly progressive distal muscle weakness and atrophy, affecting the upper and lower limbs in a child's first decade of life, leaving patients with decreased reflexes and sensory impairment.

Dr. Smieszek is the Head of Genetics at Vanda Pharmaceuticals.

Dr. Smieszek trained at the Institute for Computational Biology and has extensive experience in several aspects of human genetic studies including case control studies from clinical sequencing, whole genome explorative analyses, precision medicine based individualized studies and pharmacogenomics. Her research focuses on genetic architecture of numerous human disorders, with a strong emphasis on neuro-genetics of ASD, sleep and circadian clock genetics. She has been involved in numerous cutting-edge genome sequencing projects to decode the pathophysiology and biomarkers for better diagnostics and therapeutics.