Georgetown researchers flag success of pilot Parkinson's drug study

Could a leukemia drug already in use prove effective in treating Parkinson's disease? Researchers at Georgetown University Medical Center say they've gathered some early clinical data from a tiny, single-arm study involving Novartis' ($NVS) Tasigna (nilotinib) that suggest the answer may well be yes.

Charbel Moussa, who directs Georgetown's Laboratory of Dementia and Parkinsonism, says he scoured the pharmacopeia to find a drug that could penetrate the blood-brain barrier and trigger a neuronal cleanup that clears toxic intracellular proteins before settling on Tasigna.

"When used in higher doses for CML, nilotinib forces cancer cells into autophagy--a biological process that leads to the death of tumor cells," Moussa said in a release. "The dose used in CML treatment is significantly higher than what we used in our Parkinson's study. It appears that in smaller doses once a day, nilotinib turns on autophagy for about four to eight hours--long enough to clean out the cells without causing cell death. Then proteins that build up again will be cleared when the drug is given again the next day."

The tiny study enrolled only 12 patients, 11 of whom completed the trial. Ten of the patients experienced what Moussa calls a meaningful clinical response. Several of the patients experienced what the investigators described as dramatic improvements in "cognition, motor skills and non-motor function improvement (such as constipation)." That includes several patients who could once again talk and one who walked again.

"Study participants with earlier stage disease responded best, as did those diagnosed with Lewy body dementia, often described as a combination of Parkinson's and Alzheimer's diseases," said Fernando Pagan, who helms the Movement Disorders Program at MedStar Georgetown University Hospital, in the release.

The researchers also reported success in hitting cerebrospinal fluid biomarkers of Parkinson's--alpha-synuclein (α-synuclein), amyloid beta-40/42 (Abeta-40/42) and dopamime--with statistically significant changes in total Tau and p-Tau. "Prior studies show that α-synuclein and Abeta 40/42 in CSF are decreased as Parkinson's worsens, while Tau and p-Tau are increased in CSF with the onset of dementia."

There are some important caveats to keep in mind, in addition to the extremely small number of patients in this pilot study. One of the most important, which the researchers freely acknowledge, is that there was no control arm to compare patients not taking Tasigna. But the researchers say that there's good reason to believe they are onto something.

"To my knowledge, this study represents the first time a therapy appears to reverse--to a greater or lesser degree depending on stage of disease--cognitive and motor decline in patients with these neurodegenerative disorders," Pagan added. "But it is critical to conduct larger and more comprehensive studies before determining the drug's true impact."

Moussa also used a lower, 300-mg dose for his study, which he plans to follow up on soon in an expanded trial that he would like to start next year.

- here's the release