The symptoms of H-ABC and multiple sclerosis are similar. Unlike neurodegenerative autoimmune diseases, the underlying myelin atrophy of the brain in H-ABC leukodystrophy is hereditary. Defects in the TUBB4A gene slow myelin production, and impaired signal transmission due to defects in the Nebens sheath leads to movement disorders similar to MS. In 2022, a UK-based company acquired worldwide rights from Children’s Hospital of Philadelphia (CHOP) in Cincinnati to an antisense nucleotide (ASO) that inhibits the activity of the TUBB4A gene.
At the end of July, SynaptixBio announced a collaboration with drug discovery specialist Evotec SE, initiated in April 2022, with the aim of expanding its pipeline with additional drug candidates for the treatment of H-ABC.
In addition to the ASO, the patent, granted to discoverer Adeline Vanderbur in 2022, also prescribes an shRNA and an RNA guide strand for CRISPR editing to target the activity of the most common p.Asp.249Asn (D249N mutation) in the TUBB4A gene. However, the collaborative drug discovery is initially focused on other ASO candidates. The aim is to prepare the first clinical trials in humans for the ASO candidate developed at CHOP. SynaptixBio also received a £490,000 grant from UK Innovate last year for the development of a second candidate for a less common TUBB4A mutation. In addition, the Food and Drug Administration granted orphan drug status to an ASO candidate for the treatment of another TUBB4A leukodystrophy (isolated hypomyelination). The virtual company relies on research service providers and CDMOs for drug development.