Two recent Huntington’s disease research announcements
Skyhawk Therapeutics
Skyhawk Therapeutics Announces positive first interim results in patients from its Phase 1 Clinical Trial of SKY-0515. SKY-0515 is an oral small molecule designed to reduce the production of both huntingtin (HTT) and PMS1 proteins - two key drivers of the underlying disease process in Huntington’s disease.
In September, they announced that researchers had tested two dose levels of Skyhawk’s drug SKY-0515, an oral RNA modulator. Ten patients who took the 9mg dose saw a 62% reduction of the mutant huntingtin (mHTT) protein in their blood levels, while another 10 who received 3mg saw mHTT levels decline by 29%. Skyhawk measured the reductions after 84 days of treatment.
Professor Ed Wild said:
"SKY-0515 is reducing mHTT protein to the most impressive extent we've seen so far in patients, and crucially the clinical and biomarker data show no safety concerns so far at any dose tested," said Ed Wild, Professor of Neurology at University College London. "It is great that we are seeing substantial PMS1 reduction as well, which should be a potent combination for treating Huntington's disease via two of its core pathogenic mechanisms. This is what success looks like at the 3-month timepoint, setting the stage for meaningful impact for people living with HD across the world – for whom an orally administered huntingtin-lowering treatment such as SKY-0515 would be truly transformative."
About the Huntington’s CAG repeats
SKY-0515 targets production of two key proteins. As described by Steve Bryson, PhD, in the Huntington’s disease news:
“Huntington’s is caused by excessive repeats of a sequence of three DNA building blocks - CAG - in the HTT gene. Too many CAG repeats leads to the production of an abnormally long version of the huntingtin (HTT) protein, which is thought to form toxic clumps in nerve cells. The repeats can progressively lengthen over time, a process called somatic CAG repeat expansion, with longer repeats associated with earlier onset and more severe disease. This may explain why most people with Huntington’s, who are born with HTT defects, don’t develop symptoms until well into adulthood. Recent studies suggest a DNA-repair protein called PMS1 contributes to Huntington’s by promoting somatic CAG repeat expansion. Deleting the gene that encodes PMS1 from a Huntington’s mouse model prevented further CAG expansion and the formation of the mutant HTT clumps.”
LoQus23 Therapeutics Ltd
LoQus23 Therapeutics Ltd (“LoQus23”), a UK based biotechnology company investigating small molecule drugs that could stop the pathogenic triplet expansion that is the cause and driver of Huntington’s disease. LQT-23, a drug which has groundbreaking potential to slow or stop the progression of Huntington’s.
LoQus23 has confirmed that it is moving forward with a new research drug, called LQT-23, which is being developed specifically for Huntington’s disease. This trial is taking another disease-modifying approach to Huntington’s disease rather than symptom management.
As stated in the press release
“LoQus23 is focused on using a structure-based approach to design small molecule drugs, which can offer more convenient administration than other approaches. Oral small molecule drugs have a strong track record in treating complex brain diseases and provide greater convenience for patients compared with other advanced treatment modalities.”
The company plans to continue pre-clinical research through 2026 and hopes to apply for permission to begin human clinical trials later this year. As with all research, this will depend on regulatory approval.
This is another step in continued progress and investment in Huntington’s disease research.
Both these companies were mentioned in Ed Wild's talk 'The Beginning of the End?' Now available to watch