Oxford-based SynaptixBio has announced the selection of its lead drug candidate, SB H-19642, for clinical development targeting H-ABC, the most severe form of TUBB4A-related leukodystrophy. The antisense oligonucleotide (ASO) represents a potential breakthrough for patients with this rare, deadly, and currently incurable genetic disorder.
ASO Mechanism Shows Promise in Preclinical Studies
SB H-19642 is an antisense oligonucleotide, a short strand of synthetic DNA designed to silence mutated genes by preventing them from producing toxic proteins. Dan Williams PhD, CEO at SynaptixBio, described the milestone as "hugely significant," expressing confidence that the candidate drug will deliver positive impacts similar to ASOs approved for other degenerative diseases such as Duchenne muscular dystrophy.
Animal testing has demonstrated encouraging results, with dangerous proteins produced by the single-gene mutation that causes H-ABC showing significantly reduced prevalence following treatment. "This means disease progression could be completely halted, and there is some evidence of symptoms being reversed," Williams stated.
The company has collaborated with global drug researcher Evotec to identify, develop, and qualify the ASO candidate. Initial testing indicates the drug is safe and stable, with demonstrated effectiveness in reducing toxic protein volumes arising from the mutated gene.
Advantages Over Gene Editing Approaches
ASOs offer several benefits compared to gene editing technologies, including high targeting specificity, fewer side effects, and broad applicability. Most significantly, ASOs are non-permanent interventions that can be discontinued if dangerous side effects emerge.
"Perhaps most importantly, ASOs target the molecular causes of disease, rather than just treating the symptoms. This makes them potentially game changing," Williams noted. The therapeutic approach involves short synthetic strands of DNA or RNA that bind to mRNA from target mutated genes, preventing translation into dangerous proteins.
Growing Market and Regulatory Success
The ASO therapy market is experiencing dramatic growth, valued at $4.4 billion in 2023 and projected to reach $19.7 billion by 2032, representing an 18% compound annual growth rate according to Global Market Insights. Key drivers include increasing prevalence of neurodegenerative and genetic disorders, growing research investments in gene expression and delivery technologies, and expanding regulatory approvals for antisense therapeutics.
ASOs have already received approval for SOD1-dependent ALS (Motor Neuron Disease) and are currently in trials for Alzheimer's disease at University College London Hospital, where they have demonstrated promising results. The technology is also being investigated for Parkinson's disease and other neurodegenerative conditions.
Funding and Clinical Development Plans
SynaptixBio recently secured a £2 million BioMedical Catalyst grant from Innovate UK to support first-in-human clinical trials of its H-ABC therapeutic. This funding follows an earlier grant received in November 2023 from Innovate UK to expand the company's rare disease therapy research.
The company emphasized the importance of early disease identification, with Williams noting that the H-ABC Foundation has been instrumental in raising awareness about the devastating impacts of this condition. "It is particularly important that such rare diseases are identified as early as possible; delayed and misdiagnoses can lead to years of unnecessary suffering," he stated.
Patient advocacy groups have played a crucial role in increasing awareness of genetic disorders that ASOs can address, effectively campaigning to educate the public, medical community, and governments about the nature and impacts of these conditions.
