molecules of the month

Context. Branaplam (Novartis Institutes for Biomedical Research) is an oral brain-penetrant splicing modulator, originally developed as a small molecule splicing modulator for spinal muscular atrophy (SMA). It turns out to also lower huntingtin levels and is being developed (with Fast Track Designation) for patients with Huntington’s Disease which is driven by mutant huntingtin prion. It is expected that treatments that reduce levels of the toxic mutant huntingtin protein (mHTT) in the brain will slow progression of the disease. Current treatments only target symptoms of the disease, while the more effective therapeutic modalities such as antisense oligonucleotides and RNAis which focus on lowering mHTT levels require delivery techniques that are not ideal in clinical settings. These challenges make an agent such…