Research & Discovery

December 14, 2017 | Christopher DeFrancesco '95 (CLAS) - UConn Health

UConn Health Huntington’s Disease Expert Optimistic About New Drug

The director of the state's only Huntington's disease program explains why a recent clinical trial is encouraging news in the effort to treat Huntington's disease.

MRI brain scan (Getty Images)

Dr. Glenn Konopaske, director, UConn Health Huntington’s Disease Program (Photo by Janine Gelineau)

A recent study out of the U.K. is giving hope in the search for a breakthrough treatment of Huntington’s disease. Huntington’s disease is an inherited progressive brain disorder that affects 30,000 people in the U.S. by impacting emotional control, cognitive ability and movement. It has no cure and is eventually fatal. Though not involved in the British trial, Dr. Glenn Konopaske, director of UConn Health’s Huntington’s Disease Program, has been following the research closely, and shares his observations with UConn Today.

What did this trial find?

This was an early-phase clinical trial (Phase 1/2a) that focused mainly on safety. It was done on a relatively small number of patients with Huntington’s disease (HD), a progressive, fatal, neurodegenerative disorder that typically affects adults starting in their 30s or 40s. The treatment, called “IONIS-HTTRx,” involves an antisense oligonucleotide (ASO), or synthetic strand of DNA, that blocks the brain’s ability to make huntingtin protein, which is mutated in HD. The mutated huntingtin protein leads to cell death in the brain producing symptoms. By lowering the amount of mutated protein this treatment could halt or dramatically slow down the progression of the disease. In the study, the treatment was found to be safe and it reduced the amount of mutant huntingtin protein in a dose-dependent fashion, meaning that patients who got a higher dose of ASO had a greater reduction in mutated protein.

Why is this trial encouraging?

This is the first intervention that is showing real promise to slow or even halt the progression of HD. IONIS pharmaceuticals also developed an ASO that was recently FDA-approved for spinal muscular atrophy (SMA). In fact, it was so effective the trial was cut short. Thus we know this technology is safe in humans and can work.

HD is caused by a single gene mutation. The gene was discovered in 1993 and the HD community has waited a long time for a treatment that actually affects the natural history of the disorder. At lot can go wrong between now and FDA approval, but we are cautiously optimistic that IONIS-HTTRx might be such a treatment.

What did the study not tell us?

Unfortunately, the study wasn’t long enough to demonstrate whether lowering the amount of mutated protein had clinical benefit. But the good news is, earlier studies in animals suggests that it likely will.

What are the current options for treating Huntington’s disease?

All of the current treatment options for HD address only symptoms. There are two FDA-approved drugs for HD, but they only treat chorea, or abnormal involuntary movement. There is no currently approved treatment that will slow down or halt the progression of HD.

Tell us about UConn Health’s Huntington’s Disease Program.

We are the only HD program in the state of Connecticut. We’re located on the third floor (east) of the Outpatient Pavilion and provide multidisciplinary care to patients with HD. In addition, we are active in research and education.

We are currently a site for Enroll-HD, which is an international, longitudinal, observational study on HD. It is designed to study the natural history of HD and more importantly to develop metrics to be used to assess the effectiveness of potential treatments such as IONIS-HTTRx. When IONIS-HTTRx enters Phase 3 clinical trials, as we anticipate it will, we intend on trying to become a study site.

Note: More information about the Enroll-HD trial is available by calling 860.679.4441.