Design Therapeutics is Biotechnology company developing DT-216, which is a potential treatment for Friedreich’s ataxia (FA).
FA is caused by a change to the frataxin gene. Genes are made up of the A, T, G and C building blocks. People with FA have a high number of GAA repeats in their frataxin gene, compared to people that do not have FA. DT-216 is a GeneTAC™ molecule which targets the GAA repeats, restoring the function of the gene. The frataxin gene is used to create a message called frataxin messenger RNA (or mRNA). They hope that DT-216 will therefore increase the amount of frataxin mRNA in people with FA.
Results of the Phase 1 trial
Design Therapeutics recently reported initial results from their Phase 1 clinical trial of DT-216 in people with FA. The results showed that DT-216 was well tolerated (meaning there were no serious adverse reactions), and did increase the amount of frataxin mRNA in muscle samples taken from people with FA that had received the treatment.
The trial, which took place in the US, enrolled 29 adults with FA, and they received either placebo (no treatment), or 100mg, 200mg or 300mg of DT-216.
In their press release, Design Therapeutics state that these results support the continued development of DT-216. However, they are concerned that higher doses could lead to worsening of injection site thrombophlebitis (inflammation at the injection site). They have therefore decided to shift focus to developing an improved formulation. They hope that this will enable them to give higher doses and chronic administration, without worsening of the injection site thrombophlebitis. They will conduct nonclinical studies on the new formulation, and hope to begin a Phase 1 trial to test the new formulation in people with FA in the second half of 2024.
We previously reported on the results of the first part of this trial, in which people with FA received placebo or a single dose of DT-216. Read more here.
Observational Biomarker Study
In parallel to the Phase 1 study, they conducted an observational study to evaluate FA biomarkers. Biomarkers are a measure of the progression of FA, and can be used to evaluate whether a treatment is successful in a clinical trial. Good biomarkers are crucial for the success of clinical trials.
In the observational study, they measured the amount of frataxin mRNA and frataxin protein in blood and skeletal muscle samples from people with FA, FA carriers, and people that do not have FA. They found that frataxin mRNA levels were different in muscle samples from people with FA, FA carriers and people that do not have FA. They believe this supports the use of muscle frataxin mRNA as a biomarker for FA.
Read the full press release here.