A global clinical trial has commenced, marking a significant step forward in the quest to treat Huntington's disease, a debilitating and currently incurable genetic disorder. The trial focuses on ALN-HTT02, an investigational RNA interference (RNAi) therapeutic developed by Alnylam Pharmaceuticals in collaboration with Regeneron Pharmaceuticals. The first patient has already received the therapy at University College London Hospitals NHS Foundation Trust (UCLH).
The trial aims to recruit up to 54 participants who will receive either a single dose of ALN-HTT02 or a placebo. Those initially receiving the placebo will have the option to receive ALN-HTT02 at a later stage. The primary goal is to evaluate the safety and tolerability of ALN-HTT02 in humans, while also exploring its potential to modify the course of Huntington's disease.
Targeting the Root Cause
Huntington's disease is caused by a mutation in the huntingtin (HTT) gene, leading to the production of a toxic protein that accumulates in brain cells, causing damage and ultimately cell death. ALN-HTT02 is designed to specifically target a region of the HTT gene known as exon 1, which is believed to be a key driver of the disease's pathology. By reducing the production of the mutant huntingtin protein, the therapy aims to slow down or halt the progression of the disease.
Professor Sarah Tabrizi, director of the Huntington's Disease Centre in London and a consultant at UCLH, emphasized the importance of the trial, stating, "We are very excited about this trial as the drug, ALNHTT02, targets a specific region of the HTT gene called exon 1, which we now think is a key toxicity driver of the damage seen in Huntington's disease... Our end goal is to explore the potential of this medicine to slow disease progression and, in this first-in-human study, we are evaluating the safest ways to use ALN-HTT02."
Administration and Mechanism
ALN-HTT02 is administered via an injection into the cerebrospinal fluid surrounding the spinal cord, allowing it to reach the brain and target the HTT gene. As a small interfering RNA (siRNA) molecule, ALN-HTT02 works by selectively silencing the expression of the mutant HTT gene, thereby reducing the production of the harmful protein.
Huntington's Disease: A Devastating Condition
Huntington's disease affects an estimated 7,000 people in the UK. It is an inherited disorder, meaning that individuals with a parent carrying the faulty gene have a 50% chance of developing the condition. Symptoms typically manifest in adulthood and include memory problems, depression, movement difficulties, and impaired swallowing, speaking, and breathing. The disease is progressive and typically leads to death 10 to 30 years after the onset of symptoms.
Kevin Sloan, a vice president at Alnylam, expressed enthusiasm for the collaboration and the potential of ALN-HTT02, stating, "We're thrilled to be collaborating with established leaders in the space to advance an investigational RNAi therapeutic that we believe has the potential to alter the course of this devastating disease."
Charles Sabine, a journalist and global spokesman for Huntington's disease patients and families, highlighted the importance of patient participation in clinical trials, stating, "The science is now at a point that new therapies are being tested and giving us real hope for the future."
