Dr. Ira Shoulson, the founder of the Huntington Study Group, passed away on May 12th of 2024 at 78 years old. Dr. Shoulson was a husband, father of two, grandfather of two, and mentor, collaborator and friend to countless in the HD community and beyond.
Gene-Hunter
Dr. Ray Dorsey, Robi Blumenstein, and Dr. Karen Anderson were among the many who have been enriched by Dr. Shoulson’s life, and they each spoke about him at the November 2024 HSG meeting in Cincinnati.
Dr. Dorsey explained that Dr. Shoulson was a young neurologist who had just completed a fellowship at the NIH with Dr. Tom Chase, when he became interested in HD.
“He had great organizational skills and a burning desire to reduce the burden of Huntington’s disease and other neurological disorders,” he said.
Dr. Dorsey related how the indomitable Nancy Wexler, whose mother had died from Huntington’s disease, set out to identify the genetic cause of HD in 1979. To help her, she recruited Dr. Shoulson, as well as physicians Dr. Anne Young and Dr. Jack Penney, to join her on trips to remote villages in Venezuela where HD cases were highly concentrated.
Together, they would transform the course of HD research.
“For over a decade of many harrowing trips, Nancy, Anne and Dr. Shoulson listened to and examined countless individuals,” Dr. Dorsey said. “They created family trees that covered walls and collected thousands of blood samples, which they sent back to Boston for evaluation.”
In 1983, the team discovered the genetic marker for the disease, and ten years later, the huntingtin gene itself.
“This seemingly impossible task made headline news, transformed the field, set the stage for the Human Genome Project, and opened the door to the genetics era in which we live today,” Dr. Dorsey said.
With the cause in hand, Ira turned his eyes toward new treatments.
Leader and Mentor in Care and Research
Dr. Shoulson spent decades of his career working at the University of Rochester Medical Center (URMC), from which he received his medical degree and training in neurology. There, he was the inaugural Louis C. Lasagna Professor of Experimental Therapeutics.
He then headed to Georgetown University, where he directed the Program for Regulatory Science and Medicine, before returning to URMC in 2018 as professor of neurology and the Center for Health & Technology.
He also served as associate editor of JAMA Neurology, an elected member of the National Academy of Medicine and as a member of the National Institute of Neurological Disorders and Stroke Council and of the American Society for Experimental Neurotherapeutics.
In 2017, he founded Grey Matter Technologies, a company with the goal of improving communication, clinical care, and research in HD.
He was also devoted to treatments for Parkinson’s disease, founding the Parkinson Study Group in 1985, later being awarded the Robert A. Pritzker Prize from the Michael J. Fox Foundation.
In 1993, his work in Huntington’s disease led to the creation of an organization that would prove pivotal in enabling HD research progress.
“He knew that to evaluate therapies for HD, there needed to be a network of investigators, so in 1993, Ira and Jack Penney formed the Huntington Study Group,” Dr. Dorsey said.
Shortly after that, he established the Unified Huntington’s Disease Rating Scale, UHDRS®, as a standard to measure symptoms.
Undaunted Investigator
On the therapeutic front, his HSG team worked tirelessly to find treatments.
“No one tried harder or failed more to develop therapies for HD than Ira,” Dr. Dorsey said. He investigated countless therapies, including the GABAergic imidazole-4-acetic acid in 1975, muscimol in 1978, baclofen in 1989, fluoxetine in 1997, ethyl-EPA in 2008, minocycline in 2010, and coenzyme Q10 in 2017. None of these ultimately met with success.”
“However, for Ira, failure was only a prerequisite for success. At last, success came through his work with URMC colleague Dr. Fred Marshall and other TETRA-HD investigators and coordinators. In 2008, the FDA approved tetrabenazine as the first treatment for Huntington’s disease. Additional VMAT2 inhibitors would follow,” Dr. Dorsey said.
Later, Dr. Shoulson served as principal investigator of two landmark NIH clinical trials — Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) and Prospective Huntington At Risk Observational Study (PHAROS) — and led or helped lead more than 35 other multi-center clinical research studies. Ultimately, he was instrumental in the development of 10 new drugs for neurological disorders — seven for Parkinson disease, two for Huntington’s disease, and one for attention deficit disorder.
His efforts on the legislative front included helping Congresswoman Louise Slaughter pass the Genetic Information Nondiscrimination Act in 2008, prohibiting discrimination in employment and health insurance based on family history and genetic information.
Robi Blumenstein, president of CHDI Management, met Dr. Shoulson in 2002, as Robi began a 22-year tenure with CHDI. He recounts the volume of work that had Dr. Shoulson’s stamp on it even in the early 2000s.
“Just in 2003 alone, Ira’s accomplishments read like a lifetime achievement award: founding the Huntington Project, the SET-HD project, leading trials for Novartis and Amarin drugs, and computerization of the Clinical Trial Coordination Center, to name just a few.”
An Advocate for Patient Connection
While leading efforts in research, advocacy and organizational infrastructure, and mentoring scores of junior researchers and clinicians, he also cared for thousands
of patients in clinic, evaluating and finding best treatments for each, and always modeling empathy and respect.
Dr. Anderson recalls, “Ira once told me that when he was seeing patients, he liked to do a blood pressure measurement on each person himself, because touching them during the exam was such an intimate way to make a connection with someone.”
Robi remembers how Dr. Shoulson helped ensure that the HD scientific community forged bonds with patients.
“Among the things I learned from Ira was the importance of understanding clinical research as an interaction among clinicians/scientists and people with HD. He said, ‘We are not doing trials merely for the sake of doing trials; we are not getting drugs approved so we can say we got drugs approved. This idea that treatments must make a real difference requires engagement with the people being treated and their families.’ That was a guiding principle of Ira’s career down to the very end,” Robi said.
Dr. Shoulson described his last 10–15 years of work as his “second act,” where he focused on regulatory science and patient-reported outcomes. He never faltered in conceiving of new ideas for improving these landscapes or training those in the pipeline.
Dr. Anderson described his persuasive “way” with people as he continued to grow the individuals who would continue his mission.
“Ira was a fantastic mentor and sponsor to so many of us, in the sense that he actively looked for opportunities to pass along to us. By his own admission, he loved starting things, and brought this infectious energy to every opportunity,” she said.
“I know many of us had the experience of the gravelly-voiced phone call with an ‘offer we could not refuse’ on Ira’s latest project, or one he heard about. He was quite the salesman, but in many ways, his greatest talent was selling to all of us the idea that one could have a career in clinical research in a rare disease.”
Despite his presumptions that you would buy into his plans, Dr. Anderson says he was consistently kind, respectful and empathetic with everyone his life touched. He was patient with the most junior of people within the HD community who sought his advice, and interested in advancing their careers.
An Inspiration for Generations to Come
Dr. Shoulson’s accomplishments would not have had the great impact they did had it not been for these personal characteristics, as expressed in these final thoughts at the HSG meeting.
“I have seen such outpouring of sadness, but also gratitude from all the HD families Ira knew during his long career. So many patients and care-partners have told me how Ira encouraged them, supported them and, above all, listened to them,” Dr. Anderson said.
“A colleague described his mission in this way: ‘Ira’s embrace of new ideas and his organizational skills took neurology from a field characterized by therapeutic nihilism to one bristling with new therapies’,” Robi said.
“Despite Ira’s leadership, Anne’s genius, and Nancy’s passion, Huntington’s disease remains. Ira would take enormous delight in those who help end this terrible disease through prevention, treatment or cure, but he leaves behind unfinished business,” Dr. Dorsey said.
“That work is now left to a new generation of investigators and leaders, to coordinators and clinicians, to scientists and executives, to rising stars and unsung heroes, to advocates and families, and to dedicated individuals here and around the world who seek and will find treatments that change the course of HD for all and for all time.”