Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a fatal motor neuron disease that causes people to gradually lose control of their muscles. There is no cure, and current treatments focus on reducing symptoms and providing supportive care. Reporting June 1 in the journal Cell Stem Cell, researchers from Japan show in an early clinical trial that the Parkinson’s disease drug ropinirole is safe to use in ALS patients and delayed disease progression by 27.9 weeks on average.
Some patients were more responsive to ropinirole treatment than others, and the researchers were able to predict clinical responsiveness in vitro using motor neurons derived from patient stem cells.
To test ropinirole’s safety and effectiveness in patients with sporadic (i.e., non-familial) ALS, the team recruited 20 patients receiving care at Keio University Hospital in Japan. None of the patients carried genes predisposing to the disease, and, on average, they had been living with ALS for 20 months.
To determine whether the drug was effective at slowing the progression of ALS, the team monitored a variety of different measures throughout the trial and for 4 weeks after treatment concluded.
These included changes in the patients’ self-reported physical activity and ability to eat and drink independently, activity data from wearable devices, and physician-measured changes in mobility, muscle strength, and lung function.
Patients who received ropinirole during both phases of the trial were more physically active than patients in the placebo group. They also showed slower rates of decline in mobility, muscle strength, and lung function, and they were more likely to survive.
The benefits of ropinirole relative to the placebo became increasingly pronounced as the trial progressed. However, placebo group patients who began taking ropinirole halfway through the trial did not experience these improvements, which suggests that ropinirole treatment may only be useful if treatment is started earlier and administered over a longer duration.
Next, the researchers investigated the mechanisms behind ropinirole’s effects and looked for molecular markers of the disease. To do this, they generated induced pluripotent stem cells from the patients’ blood and grew these cells into motor neurons in the lab. Compared to healthy motor neurons, they found that motor neurons from ALS patients showed distinct differences in structure, gene expression, and metabolite concentrations, but ropinirole treatment reduced these differences.
The researchers say that this suggests that this method — of growing and testing motor neurons from patient-derived induced pluripotent stem cells — could be used clinically to predict how effective the drug would be for a given patient.
It’s unclear why some patients are more responsive to ropinirole than others, but the researchers think that it’s probably due to genetic differences that they hope to pinpoint in future studies.
Satoru Morimoto, Shinichi Takahashi, Daisuke Ito, Yugaku Daté, Kensuke Okada, Chris Kato, Shiho Nakamura, Fumiko Ozawa, Chai Muh Chyi, Ayumi Nishiyama, Naoki Suzuki, Koki Fujimori, Tosho Kondo, Masaki Takao, Miwa Hirai, Yasuaki Kabe, Makoto Suematsu, Masahiro Jinzaki, Masashi Aoki, Yuto Fujiki, Yasunori Sato, Norihiro Suzuki, Jin Nakahara, Hideyuki Okano. Phase 1/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery. Cell Stem Cell, 2023; 30 (6): 766 DOI: 10.1016/j.stem.2023.04.017
Cell Press. (2023, June 2). Parkinson’s disease drug ropinirole safely slowed the progression of ALS for over 6 months in a clinical trial. ScienceDaily. Retrieved June 2, 2023 from www.sciencedaily.com/releases/2023/06/230602115106.htm
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