Parkinson’s drug shown to slow ALS progression in clinical trial
An early clinical trial has shown that the Parkinson’s drug ropinirole is safe to use in patients with the fatal motor neurone disease amyotrophic lateral sclerosis, and delayed disease progression by an average of 27.9 weeks.
ALS causes people to gradually lose control of their muscles and while the disease can strike at any time of life, symptoms most commonly develop between the ages of 55 and 75. Men are more likely to develop ALS than women.
There is currently no cure for ALS – which is also known as Lou Gehrig’s disease – with available treatments focussing on reducing symptoms and providing supportive care.
Researchers at Keio University School of Medicine in Japan have reported their findings in the journal Cell Stem Cell.
Senior author and physiologist Hideyuki Okano of the Keio University School of Medicine in Tokyo, said: “ALS is totally incurable, and it’s a very difficult disease to treat.
“We previously identified ropinirole as a potential anti-ALS drug in vitro by iPSC (Induced pluripotent stem cells) drug discovery, and with this trial, we have shown that it is safe to use in ALS patients and that it potentially has some therapeutic effect, but to confirm its effectiveness we need more studies, and we are now planning a phase 3 trial for the near future.”
To test ropinirole’s safety and effectiveness in sufferers with sporadic (non-familial) ALS, the team recruited 20 patients receiving care at Keio University Hospital. None of the patients carried genes predisposing them to the disease, and, on average, they had been living with ALS for 20 months.
The trial was double blinded for the first 24 weeks, meaning that the patients and doctors did not know who was receiving ropinirole and who was being given a placebo.
Then, for the following 24 weeks, all patients who wished to continue were knowingly administered ropinirole.
Many patients dropped out along the way – partially due to the Covid-19 pandemic. This meant only seven out of 13 ropinirole-treated and one out of seven placebo-followed-by-ropinirole-treated patients were monitored for the full year.
However, no patients dropped out due to safety reasons.
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 four weeks after treatment finished. 
These included changes in the patients’ self-reported physical activity and ability to eat and drink independently, and data from wearable devices and physician-measured changes in mobility, muscle strength, and lung function.
First author Satoru Morimoto, a neurologist at the Keio University School of Medicine, said: “We found that ropinirole is safe and tolerable for ALS patients and shows therapeutic promise at helping them sustain daily activity and muscle strength.”
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. The researchers said it suggests that ropinirole treatment may only be useful if it’s started earlier and administered over a longer duration.
Dr Morimoto said: “We found a very striking correlation between a patient’s clinical response and the response of their motor neurons in vitro. Patients whose motor neurons responded robustly to ropinirole in vitro had a much slower clinical disease progression with ropinirole treatment, while suboptimal responders showed much more rapid disease progression despite taking ropinirole.”
It’s unclear why some patients are more responsive to ropinirole than others, but the researchers think this is probably due to genetic differences it’s hoped will be pinpointed in future studies.
The researchers findings have met with a mixed response from neurological experts and others working in the field of motor neurone disease.
Michael Swash, professor of Neurology at Barts and the London School of Medicine in the UK, said the Keio report was of interest. “There has long been an effort to find an ‘off the shelf medication’ applicable to ALS management. Ropinirole may be one such drug.
“But there needs to be a clearer understanding of its mechanism of action in order to apply such knowledge more widely. In addition, a larger study is required to understand who might benefit and what might be the limits of practical therapy in using ropinirole in ALS.
“More data on possible unwanted effects are also required. There are interesting parallels in proteinaceous accumulation in the neuronal cytosol between PD and ALS that should be explored.”
Dr Brian Dickie, director of research at the MND (Motor Neurone Disease) Association, added: “Whilst these results may be of some interest to the research community, the clinical trial is far too small and the findings too preliminary to draw any valid conclusions.”
