Your HTT gene encodes for the production of huntingtin, a protein that helps your neurons (nerve cells in your brain) function correctly. When mutations happen in this gene, the protein becomes abnormal. This mutated protein forms long, toxic strands that bind to neurons and cause them to die. Unfortunately, when people develop this condition – called Huntington’s disease – there are no cures and no way to reverse the damage. More research has been looking into reducing mutant huntingtin levels in the body to see whether that could slow or even reverse disease progression.
PTC Therapeutics, a global biopharmaceutical company, recently shared an update on the Phase 2 PIVOT-HD trial which is assessing the impact of PTC518 on Huntington’s disease. PTC518 is an oral small-molecule treatment that can penetrate the blood-brain barrier (BBB); it is designed to reduce mutant huntingtin levels. In the first portion of the trial, the research team has explored the drug’s safety, efficacy, pharmacokinetics, and pharmacodynamics. The second portion of the study, which will take place later this year, will include a dose-escalation and dose-exploration portion. The company plans to evaluate both 5mg and 10mg PTC518, though they are also considered testing a third dose.
Interim data from the first part of the trial showed that PTC518 reduced mutant huntingtin levels by an average of 30% at the higher dose. Data reaffirms that PTC518 can cross the BBB, allowing for more targeted and sustained treatment. Additionally, the drug was found to be well-tolerated with minimal or no serious side effects.
Additional Information on Huntington’s Disease (HD)
In most cases, Huntington’s disease is considered adult-onset. It often manifests when people are in their 30s or 40s. After symptoms appear, the typical lifespan is 10-15 years. However, in rarer cases, this progressive neurodegenerative disease can occur in younger people. This form is called juvenile-onset and it is considered more aggressive than the adult-onset form. An estimated 3-7 out of every 100,000 people have Huntington’s disease.
This condition can cause startling and extreme transformations. Continuing research and advancing education is crucial to change the prognosis.
Symptoms of Huntington’s disease include changes in mood, behavior, or personality; anxiety, depression, and impulsivity; involuntary twitching or writhing movements; difficulty speaking and swallowing; poor balance and coordination; forgetfulness; poor decision-making; difficulty retaining new information; an abnormal gait; muscle stiffness or rigidity; and weight loss.
While there are a few therapies designed to reduce chorea (involuntary movements), and other symptoms can be managed with various medication, there are no disease-specific cures.
