In observance of Huntington’s disease (HD) awareness month in May, we turn our attention to a disorder that has been recognized since the Middle Ages and described in English in 1872. This autosomal dominantly inherited disease is named after the 22-year old physician, George Huntington. The genetic cause had been unknown until the Huntington’s Disease Collaborative Research Project identified the responsible gene in 1993.
We asked ANA member Samuel A. Frank, MD to share an update on the state of the disease and his own HD research. Dr. Frank is a movement disorder neurologist at Beth Israel Deaconess Medical Center (BIDMC), a teaching hospital for Harvard Medical School. He served as the principal investigator for a Huntington Study Group study and on the HSG executive committee. He was a member of the HDSA Board of Trustees and currently directs the HDSA Center of Excellence at BIDMC, and is the inpatient neurology consultant for the specialized HD service at Tewksbury Hospital.
Q. How are treatment options for Huntington’s disease different today from 10 years ago?
The first FDA-approved medications for chorea associated with HD was approved in 2008 and the second in 2017. While these medications are not disease modifying, they can improve some of the symptoms to help with safety and quality of life.
"The current era is the most hopeful and optimistic period in Huntington's disease history."
Q. What promising research is poised to change the standard of treatment for Huntington’s disease?
There are many approaches under study and in development at this time. The current era is the most hopeful and optimistic period in HD history. Based on our understanding of the genetics of HD as well as advancing technology, there are multiple approaches to study ways to lower mutant huntingtin, interfere with neuroinflammation using monoclonal antibodies, and continued development of potential symptomatic treatments.
Q. What work is your lab undertaking to move understanding or treatment for Huntington’s disease forward?
My work is entirely human-based. BIDMC participates in foundation and industry-sponsored research to better understand HD and to test potential new symptomatic and disease-modifying therapies.We have multiple ongoing projects which include:
- Enroll-HD is a worldwide observational study for patients with Huntington’s disease and their families. Comprising more than 20,000 people in total, the study is designed as a clinical research platform that will enable health care professionals, scientists, and families affected by this illness to work together toward an improved understanding of Huntington’s disease and aid in the development of new treatments.
- The SIGNAL Trial is a Phase 2 multi-center, randomized study being conducted at approximately 30 sites across the United States and Canada in collaboration with the Huntington Study Group. This trial is a new investigational approach to early treatment that employs an immunotherapy approach. This trial is for people with the Huntington’s gene mutation who either have early stages of disease or have subtle findings without a diagnosis of Huntington’s disease yet. This study has shown promise in slowing disease progression.
- Generation-HD1 is a new clinical study of Roche’s investigational therapy for Huntington’s disease, which began enrolling participants in early 2019. BIDMC is the only study site in New England, and one of 20 sites in the U.S. This study is evaluating the safety and efficacy of an Anti-Sense Oligonucleotide (ASO) therapy.
- Feasibility of Eye Movement Analysis in HD is funded through the Huntington Society of America Human Biology Projects pathway. Using available technologies, we are evaluating whether or not eye movements may be able to detect the onset and progression of HD through quantification of certain eye movements.
Q. How has the ANA supported your career or work in this area?
I have been a member since 2014, and the chair of my department is Annals of Neurology Editor Clifford Saper, so the ANA has certainly helped with my career through many department affiliations and collaborations.