Huntington's disease drug clears initial hurdles - raising hopes

By Dr. Ananya Mandal, MDDec 11 2017

Huntington’s disease is a genetic disorder that affects the brain progressively and has no known cure till date. In a breakthrough, the first drug that can target and reduce the cause behind this dreaded disease has been found to be effective, safe and well tolerated in a human clinical trial that was conducted by UCL scientists.

The protein associated with the disease is called huntingtin protein and this drug successfully lowered the levels of this protein and reduced the harm caused to the nervous system.

The new drug IONIS-HTTRx has been in the pipeline for over ten years now being tried on laboratory animals and in the labs. This was the first human trial that was conducted with the new drug. The trial began in the last months of 2015 and was led by Professor Sarah Tabrizi UCL Institute of Neurology, Director of the UCL Huntington’s Disease Centre and IONIS-HTTRx Global Chief Investigator. It was supported by Ionis Pharmaceuticals.

The trial involved 46 patients with early Huntington’s disease in 9 different study centres spanning across United Kingdom, Germany and Canada making it a multi-centric trial. These patients were divided into two groups – one to receive the test drug and the other to receive placebo. The patients were given four doses of the new drug or placebo that was injected into the spinal fluid of the patient so that it reached the brain.

As the trial progressed, this dose was raised to change the design into an ascending dose trial design. At every step patient safety and well being was assessed along with the effectiveness of the drug.

At the end of the trail this week, the researchers announced that the drug was deemed safe and well tolerated among the human participants. According to Professor Tabrizi, “The results of this trial are of ground-breaking importance for Huntington’s disease patients and families. For the first time a drug has lowered the level of the toxic disease-causing protein in the nervous system, and the drug was safe and well-tolerated. The key now is to move quickly to a larger trial to test whether the drug slows disease progression.”

The trial was to assess the safety as well as a the effectiveness of the new drug. Huntingtin protein levels are markers of this disease. The team used an ultra sensitive assay to measure the concentrations of the protein in the patient’s spinal fluid both before and after treatment. They found that IONIS-HTTRx­ could successfully lower the levels of the mutant huntingtin.

With this significant success, Ionis’ partner, Roche now would license IONIS-HTTRx and take further responsibility for the development, regulatory approval and final marketing of the drug. Ionis has announced that all the patients who were part of this pilot trial would not be part of an extension of the trial to receive IONIS-HTTRx.

The results of the present trial are being prepared to be presented at scientific meetings and published in scientific journals. The study was supported by The National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre

Huntington’s disease typically starts in the 30s or 50s and worsens with time. If one parent has this disease, the chances of the child getting it are 50 percent. At present around 10,000 people in UK and 30,000 people in America are living with Huntington’s disease. There is a problem at the genetic level especially at the huntingtin gene that codes for the huntingtin protein. This huntingtin protein is necessary for the normal development of the brain cells.

Reference: https://www.ucl.ac.uk/news/news-articles/1217/111217-huntingtons-disease-protein