PTC Therapeutics: avviata la sperimentazione della molecola PTC518 per il trattamento della malattia di Huntington

PTC Therapeutics has started in-human Huntington’s disease trial with PTC518


In an official statement of 17 November 2020, PTC Therapeutics announced the initiation of a Phase 1 clinical trial to evaluate PTC518 in healthy volunteers. The Phase 1 study includes both single and multiple ascending dosing regimens that will help establish the safety, pharmacology, and dose selection for the Phase 2 study.

In PTC’s trial, two different dosing regimens will be tested: single and multiple ascending dosing. In the single ascending regimen, participants will only receive one dose of the drug candidate. In the multiple ascending regimen, each participant will receive multiple doses. 

Data from the Phase 1 study are expected to be available in the first half of 2021.

PTC518 is an orally bioavailable molecule with broad central nervous system and systemic distribution. Like all ASOs, it is designed to target Huntingtin protein expression with high selectivity and specificity. PTC518 has favorable pharmaceutical properties and in animal studies, has been found to lower the level of the disease-causing huntingtin protein. This lowering has also been found to be dose-dependent: the higher dose of PTC518, the greater lowering of huntingtin.  

The PTC518 molecule would act on the mRNA splicing mechanism by specifically reducing the expression of the huntingtin protein. Splicing is a biological phenomenon that aims to clean up a gene from the less functional parts. During splicing, introns (non-coding regions) are removed and exons (coding regions) are joined together, leading to the synthesis of alternate proteins that play an important role in the human physiology and disease. Through a splicing mechanism, PTC518 inserts a stretch of synthetic DNA between the exons to facilitate the degradation of the mRNA. 

The researchers believe that even a non selective reduction of the mutated protein, represents a potential benefit the disease’s treatment. Huntingtin mRNA and protein levels will be measured to gain early proof of splicing mechanism in humans as was done in the risdiplam SMA development program. 

Stuart W. Peltz, Ph.D., Chief Executive Officer, PTC Therapeutics, recently stated that the launch of a trial with a small therapeutic molecule through a convenient oral administration, has the potential to change the treatment landscape for Huntington's disease. 

"The effect of an oral ASO therapy that acts also on the expression of the huntingtin protein in the periphery and not only within the nervous system, represents a great opportunity for the treatment of HD, subject to compliance with the criteria of prudence in the interest of the patients’ community” - stated Ferdinando Squitieri, LIRH Foundation Scientific Director and Head of the Huntington Unit at IRCCS Casa Sollievo della Sofferenza and CSS-Mendel.

Read the official Press Release