Phase 1b Trial Will Test Nilotinib’s Safety, Tolerability in Huntington’s Patients

A Georgetown University Medical Center (GUMC) Phase 1b clinical trial is recruiting patients to test the safety and tolerability of a leukemia treatment called nilotinib in Huntington’s disease patients.

The research team plans to initially enroll 10 patients with early to moderate Huntington’s. Patients will receive 150mg of oral nilotinib for three months. The treatment’s effects on cognitive, motor and psychiatric symptoms will also be assessed.

Nilotinib is a tyrosine kinase inhibitor that blocks a protein called BCR-ABL, whose activity is uncontrolled in cancer, leading to cell proliferation. This protein is also implicated in oxidative stress — cellular damage that occurs as a consequence of high levels of oxidant molecules, such as free radicals or reactive oxygen species.

It is sold under the trade name Tasigna (by Novartis) in the U.S. and Europe for the treatment of chronic myeloid leukemia.

The trial will be led by Karen E. Anderson, MD, director of the Huntington’s Disease Care, Education and Research Center at GUMC. It will be partially funded by Cures Within Reach, a philanthropy that works to leverage the speed, safety and cost-effectiveness of repurposing research for quicker development of a wider range of therapeutic options.

For more information about the trial, contact Hope Heller by email or call 202-687-1366.

“Cures Within Reach is proud to support Dr. Anderson’s work, and other repurposing research clinical trials like hers,” Clare Thibodeaux, PhD, the philanthropy’s director of scientific affairs, said in a press release. “By catalyzing repurposing research, we have the potential to create treatments for the millions of patients suffering from an unsolved condition such as Huntington’s.”

Anderson said, “If a drug already approved for another condition is found to be safe and helps relieve symptoms of the disease, we can get a new treatment to patients and their families relatively quickly.

“This is a huge advantage in the world of drug development, where promising treatments often take years to even get into human studies after they are tested in animal models.”

Anderson cautioned that the Phase 1b study would be small and would be testing nilotinib’s safety in Huntington’s, not its efficacy. That would be the focus of larger trials in the future.

The study will be GUMC’s fourth clinical trial of nilotinib for a neurodegenerative disorder. Georgetown’s first study was a small Phase 1 trial (NCT02281474) in patients with Parkinson’s or dementia with Lewy bodies. It showed that 150  and 300  mg of the treatment candidate lowered the amount of a protein called alpha-synuclein — the main component of Parkinson’s characteristic Lewy bodies – improved patients’ motor and cognitive functions, and increased brain levels of dopamine, which are typically reduced in Parkinson’s disease.

Similar to Parkinson’s and dementia with Lewy bodies, patients with Huntington’s experience accumulation of toxic proteins, including huntingtin. However, their level of dopamine, a chemical with a key role in the control of motor function and behavior, is not significantly altered.

“Previous work with nilotinib has demonstrated that it may increase the level of dopamine, so establishing the safety of nilotinib in Huntington’s disease is important,” said Charbel Moussa, PhD, director of the Translational Neurotherapeutics Program at GUMC. “Side effects such as worsening motor and behavioral symptoms as a result of dopamine increase must be very carefully monitored.”

The team is recruiting participants for two placebo-controlled, double-blind Phase 2 trials on nilotinib – the multi-center NILO-PD study (NCT03205488) in Parkinson’s and a study in mild to moderate Alzheimer’s (NCT02947893).

Recent results of the NILO-PD trial in Parkinson’s were in line with the initial Phase 1 study, showing that treatment with nilotinib prevented the formation of toxic alpha-synuclein aggregates, and induced a rapid increase in the production and metabolism of dopamine.

Moussa is the inventor on a Georgetown-owned U.S. patent and on pending U.S. and foreign patent applications covering the use of nilotinib and other tyrosine kinase inhibitors for the treatment of neurodegenerative diseases.