In their research with HD mouse models, they found promising molecules called “splice modulators”, which have proven to reduce huntingtin. Following the testing of its molecules in mice, PTC Therapeutics moved on to develop a safety trial for the huntingtin lowering drug PTC-518.  The Phase 1 trial for PTC-518 began in late 2020 and was conducted in a limited group of people without HD to establish the safety of the drug and the adequate dose range to be used in subsequent phases of the trial. Besides proving that the drug was safe to be administered in humans, the Phase 1 results showed that PTC-518 reduced the huntingtin protein by 30% to 50% depending on the dose administered and was also able to cross the blood-brain barrier and reach the target cells. 

With these encouraging results, PTC Therapeutics has launched PIVOT-HD, a Phase 2 trial, in April 2022. The trial is designed to enroll 162 HD participants and will run in the USA, Australia, UK, France, Germany and The Netherlands. This phase 2 trial aims to “confirm the dose-dependent lowering of huntingtin protein that was demonstrated in our Phase 1 clinical study and gain insight to biomarker data that could provide meaningful evidence of treatment effect”, explains the CEO of PTC Therapeutics, Stuart W. Peltz, in their press release. 

The trial is divided in two parts: first, researchers will evaluate the PTC-518 pharmacodynamics (i.e., the action of the drug on the organism) for 12 weeks; then, researchers will evaluate the impact of PTC-518  on specific HD biomarkers for nine months. So far, the drug has been well tolerated and has shown no adverse effects. Additionally,  PTC-518 has shown higher accumulation in the brain compared to the rest of the body, which is very interesting since the brain is the main target for HD treatment.

In fact, while confronted with several news about HD trial setbacks, the Moving Forward team is really interested in following the journey of this orally administered drug and its promising results. Across the world, HD families should not lose their hope but rather encourage each other and express their gratitude to the heroes involved in the relentless HD research process.

We know that the search for an effective treatment for Huntington’s disease is a long-distance race and that families and patients have already covered many miles. Despite the fatigue, we must stick together, support each other and be hopeful with the tireless work being done by the scientific community to bring us closer to the finish line. The efforts and commitment of HD families and HD investigators in research will never be overestimated.

You can read more about PIVOT-HD here: