Educational guide

Huntington's Disease Drug Reduces Levels of Abnormal Protein in Patients

Despite it’s well known genetic underpinnings, there are currently no drugs to treat the underlying cause of Huntington’s disease (HD). However, a new study reports promising results for a new HD drug that has been found to be safe and lowers the levels of the

Written by Peptide Therapy Guide Editorial TeamPublished September 9, 2026

For education only

This guide cannot diagnose a condition or recommend a personal treatment plan. Discuss medical questions with a qualified professional.

“This is a tremendously exciting and promising result for patients and families affected by this devastating genetic brain disorder,” said Blair Leavitt, MD, professor in the department of medical genetics & medicine, division of neurology at the University of British Columbia. “For the first time, we have evidence that a treatment can not only decrease levels of the toxic disease-causing protein in patients, but that it is also safe and very well tolerated.”

The work is published in the New England Journal of Medicine, in a paper titled, “Targeting Huntingtin Expression in Patients with Huntington’s Disease.”

The experimental drug developed by Ionis Pharmaceuticals and Roche was tested in a randomized, double-blind, multiple-ascending-dose, Phase I–IIa trial involving adults with early Huntington’s disease. The trial enrolled 46 patients with early Huntington’s disease at nine study centers in Canada, the United Kingdom, and Germany. Of the 46 patients, 34 were randomized to receive the drug and 12 were randomized to receive placebo. Each participant received four doses of the drug and all study participants completed the study and have continued to receive the active drug in an on-going open-label study. The drug was administered monthly to patients via an injection directly into the cerebrospinal fluid.

The trial has demonstrated for the first time that the drug, successfully lowered levels of the mutant huntingtin protein—the toxic protein that causes Huntington’s disease—in the central nervous system of patients. While such reductions aren’t guaranteed to yield clinical benefits, the study is the first time that a targeted huntingtin-lowering agent has been shown to lower mutant protein levels.

The researchers, led by Sarah Tabrizi, MB, ChB, PhD, director of the Huntington Disease Centre at University College London, found that the drug produced significant decreases in the levels of mutant huntingtin protein in the patients’ cerebrospinal fluid. None of the patients experienced any serious adverse reactions, suggesting that the treatment is safe and well tolerated by patients.

Huntington’s disease is a fatal genetic neurological disease. It usually develops in adulthood and causes abnormal involuntary movements, psychiatric symptoms, and dementia. To date, no effective treatments have been proven to slow down progression of this disorder. Huntington’s disease is caused by a single known genetic mutation, and each child of a carrier of the mutation has a 50% chance of inheriting the disease.

The drug is currently being evaluated in a large Phase III multi-center clinical trial being performed at the Centre for Huntington Disease at UBC and other centers around the world. This study is designed to determine whether the treatment slows or halts the progression of disease symptoms.

Connected reading

Helpful context for this guide

Source-derived material selected through this article’s indexed topics.

Related questions

01How stable is the antibody?

A crucial question often addressed during preclinical development focuses on the in vivo stability of therapeutic antibodies. Increasing the half-life of a therapeutic antibody has several benefits ranging from higher treatment efficacy to increased advantages for the patients who will have a fewer number of therapy sessions and a reduced cost. Given these compelling benefits, following the identification of therapeutic antibodies with the desired specificity, developers usually subject them to a refinement step to increase their stability. This process is often hindered by the lack of reliable experimental tools to predict the half-life of antibodies in patients. The major hurdle of using mouse models to predict antibody stability in the serum lies in the way immunoglobulin proteins are processed by the organism. In mammals, most proteins circulating in the serum undergo constant uptake by endothelial cells and are routed through the endosomes to the lysosomal compartment for degradation. In the endosomes, immunoglobulin G (IgG) proteins are recognized and bound by a transmembrane protein, called the neonatal Fc receptor (FcRn), which mediates their recycling to the plasma membrane and subsequent release back into the serum. As a result, the half-life of IgGs are significantly extended by this mechanism. Since most therapeutic antibodies belong to the IgG class, this recycling system is very relevant for their relative stability in the body. Remarkably, the relative affinity between IgGs and FcRn is extremely disparate between different species, with the mouse receptor showing a much higher affinity than its human counterpart.

Source: www.genengnews.com ↗

02Undruggable or unscreenable?

Another obstacle to discovering new PPI inhibitors is the lack of libraries designed to hunt for them, points out Philippe Roche, PhD, senior scientist at the Integrative Structural and Chemical Biology team at the Cancer Research Center of Marseilles, France. “If you screen PPIs using libraries that were designed for kinases or GPCRs, that’s why you don’t get a lot of good results,” he says. To that end, his group began assembling a library focused on orthosteric inhibitors of PPIs. The result was 2P2Idb, a hand-curated, structural database cataloguing orthosteric inhibitors of PPIs for which the interface had been 3D characterized. From analyzing these known PPI inhibitors, and what structures they had in common, Roche and his colleagues developed a model to predict whether compounds would likely inhibit PPIs. Using this method, 2P2Idb creates an enriched screening library that dramatically increases the hit rate compared to standard libraries. Having proven their success with a small library of 1600 compounds, they are in the process of expanding the library to 10,000 compounds. Once that’s published, “the idea is to make this library available to labs around the world,” Roche says. “We will provide the library free of charge for people to be able to screen PPI targets.”

Source: www.genengnews.com ↗

About the author

Peptide Therapy Guide Editorial Team

Editorial team for Peptide Therapy Guide.

View all articles →

Related questions

Peptide Therapy Guide Editorial Team

Potential Leukemia Drug Target Found in Epigenetic Protein

Protein Interactions May Now Be Defined in a Quick and Efficient Manner

Mosquitoes Sense Bed Net Insecticides through Their Legs

Cancer Drug Discovery’s “RASzle-Dazzle”