Researchers at the University of British Colombia have developed a test that allows physicians to measure the effectiveness of gene silencing therapy for Huntington’s disease. The test will also support the first human clinical trial involving a drug that targets the genetic basis of the disease.

Huntington’s Disease And Huntingtin

Huntington’s is a genetic disease, usually manifesting in later years of life. It targets the brain and symptoms gradually become worse, causing coordination and movement impairment, mental problems and psychiatric issues.

The genetic mutation causing Huntington’s results in the production of a toxic mutant protein called huntingtin that causes progressive brain cell injury. Reducing the levels of huntingtin in the brain could possibly delay or prevent the onset of the disease. Several therapies based on this idea have already given promising results in animal models of Huntington’s disease, and human trials are now being considered.

The New Test Measures Effectiveness Of Treatment For Huntington’s

The research team found that levels of huntingtin in brain cells could be accurately calculated via cerebrospinal fluid collected via spinal tap. This ultrasensitive test was able to detect even minute amounts of the mutant protein, and could also trace changes in its levels in the brain over time, especially in response to new therapies.

The test was developed by Amber Southwell, Michael Hayden, and Blair Leavitt from UBC’s Centre for Molecular Medicine and Therapeutics and the Centre for Huntington Disease, along with colleagues from Mayo Clinic. A recent study published in Scientific Reports features the breakthrough.

The gene silencing therapy currently under investigation by UBC researchers aims to lower the levels of huntingtin in the brain. Leavitt stated that with the help of the devised test, many promising gene silencing therapies could not be tested for their effectiveness and could make it through to clinical trials.

A New Clinical Trial Underway

The findings have enabled Leavitt and team to initiate a clinical trial of a ‘huntingtin gene-silencing therapy’ at the Centre for Huntington Disease at the Djavad Mowafaghian, Centre for Brain Health. This new trial will investigate the efficacy of the novel treatment strategy, and is in the process of screening potential candidates. It will be the first study to evaluate the effectiveness of a drug targeting mutant huntingtin in humans.