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An expensive cancer drug may reverse late-stage Parkinson鈥檚 disease, enabling participants in a small clinical trial to speak and walk again for the first time in years. While there are several treatments for the symptoms of Parkinson鈥檚, if confirmed this would be the first time a drug has worked on the causes of the disease.

鈥淲e鈥檝e seen patients at end stages of the disease coming back to life,鈥� says of Georgetown University Medical Center in Washington DC, who led the trial.

The drug, called nilotinib, works by boosting the brain鈥檚 own 鈥済arbage disposal system鈥� to clear proteins that accumulate in the brains of people with Parkinson鈥檚 disease, says Moussa. These proteins are thought to trigger the death of brain cells that make molecules like dopamine that are needed for movement and other functions.

Nilotinib is already approved to treat cancer 鈥� it blocks a protein that drives chronic myeloid leukaemia. It also blocks another protein that interferes with lysosomes 鈥� cell structures that destroy harmful proteins. Moussa thinks that nilotinib can free up lysosomes to do a better job of clearing out proteins associated with Parkinson鈥檚 disease.

Fast improvement

Tests in animals showed promise, so Moussa, his colleague and their team set up a small trial of 12 volunteers with Parkinson鈥檚 disease or a similar condition called dementia with Lewy bodies. The trial was designed to test only the safety of the oral drug, which was given as a daily dose for six months.

Although all the volunteers were at an advanced stage of disease at the start of the trial, and three of them were unable to speak, all of them started to improve once they started taking the drug, some as little as three weeks later.

鈥淲e had people as stiff as a board at the start of the study who were walking around, sitting down and bending their legs by the end,鈥� says Moussa, 鈥淵ou could see the elation on their faces when they saw the improvement. There wasn鈥檛 a dry eye in the room.鈥�

鈥淭hey were brighter and more fluent in speech, and they had a lot more energy,鈥� says Pagan. All three of the participants who were unable to speak had begun talking again by the end of the trial. 鈥淚t was like an awakening for them,鈥� says Pagan.

New lease of life

Alan Hoffman, who first showed signs of Parkinson鈥檚 in 1997, says the nilotinib trial changed his life. As his disease worsened, he had many falls, needed his wife鈥檚 help to get out of bed and he considered taking his own life. While deep brain stimulation helped treat the rigidity of his body, it wasn鈥檛 a cure, so he enrolled in the nilotinib trial. Within a matter of weeks, he was able to make the bed, and read a book for the first time in years.

The drug was detectable in the cerebrospinal fluid of the participants, showing that it was making it through the blood-brain barrier and into the brain. The team also monitored the tau, amyloid beta, and alpha-synuclein proteins that accumulate as part of Parkinson鈥檚 disease, and found that the levels of these proteins either stabilised or fell in all participants. At the same time, dopamine levels increased. Those taking the highest dose of the drug showed the biggest changes.

Pagan presented the results at the meeting in Chicago on Saturday. By one measure, participants鈥� cognition improved by an average of around five points, on a scale of 30. While nilotinib causes unpleasant side effects in people who take high doses of it for leukaemia, much lower doses were used in this trial and the team saw no unwanted effects.

at Queensland University of Technology in Brisbane, Australia, says the results are striking. 鈥淭he new treatment certainly appears to alleviate symptoms of Parkinson鈥檚 as well as cause reduction in biomarkers associated with disease progression,鈥� he says.

Too good to be true?

The team thinks it is the first drug that can target the root cause of Parkinson鈥檚 disease and provide more than temporary relief. Other neurologists are excited by the results, but warn that no firm conclusions can be drawn until the drug has been tested in a larger trial with a placebo control.

鈥淚t seems too good to be true. I dearly hope I am wrong,鈥� says of Sandwell and West Birmingham Hospitals NHS Trust, UK.

鈥淚f it can really reverse Parkinson鈥檚, we鈥檇 have reached a major milestone, but I鈥檓 sceptical,鈥� says at King鈥檚 College London. 鈥淚 would say 鈥榳atch this space鈥�.鈥�

There have been false dawns for Parkinson鈥檚 before. A compound thought to encourage the growth of new brain cells 鈥� GDNF 鈥� received a lot of interest after promising animal experiments, and evidence suggesting it worked in a small number of people. However, no one has managed yet to replicate the effects in larger, placebo-controlled clinical trials.

The placebo effect can make a huge difference to symptoms of Parkinson鈥檚 disease, says , director of research at British charity Parkinson鈥檚 UK. 鈥淲e can鈥檛 yet say that patients will benefit.鈥�

Moussa鈥檚 team is now enrolling people with a range of disorders that involve accumulating brain proteins, including Alzheimer鈥檚 disease and amyotrophic lateral sclerosis, for a larger, placebo-controlled trial.

Expensive treatment

Sadly, the effect doesn鈥檛 last, and when the volunteers were taken off the drug at the end of the trial, they started to deteriorate again, says Moussa. Many have since tried to get hold of the drug themselves, but it costs a whopping $10,000 a month.

鈥淥ne woman sold her car to buy the drug for her husband,鈥� says Moussa. Pagan is in discussions with manufacturer Novartis, hoping that the participants can be offered continued treatment at a reduced cost on a compassionate basis, through a procedure the company already uses to . 鈥淲e鈥檝e been working on it for three months,鈥� says Pagan, 鈥渁nd hope to have an answer soon.鈥�