Cancer Drug Shows Evidence of Safety for Parkinson’s

July 11, 2016

By PDF

Nilotinib, a drug already approved for treatment of leukemia and with potential for treating Parkinson’s disease (PD) may be safe to use experimentally in PD, according to the results of a small, phase 1 clinical trial. The study appears in the July 11 online edition of the Journal of Parkinson’s Disease.

Nilotinib is drug that is already approved by the US Food and Drug Administration (FDA) as a potent treatment for certain types of blood cancers. In laboratory studies, nilotinib has been shown to have the potential to alter the course of Parkinson’s in animals, making it a candidate for clinical trials.

In this trial, researchers led by Charbel Moussa, M.D., Ph.D., at Georgetown University Medical Center in Washington, D.C., aimed to primarily test the safety of nilotinib for people with PD. Initially, 30 people were screened for the trial but 18 were turned away due to pre-existing cardiovascular issues which made the drug unsafe for them. Of the 12 eligible study participants, seven had PD and five had been diagnosed with the parkinsonism known as dementia with Lewy bodies(DLB). All participants had moderate to severe movement symptoms, ranging from three to five on the Hoehn and Yahr scale, and cognitive impairment.

Participants took nilotinib for six months at much lower doses than those prescribed for cancer — five took 150 mg/day and seven took 300 mg/day. Scientists looked for biochemical markers of the drug’s effects in participants’ cerebrospinal fluid (fluid surrounding the brain) and evaluated participants’ movement and cognitive symptoms throughout the study. All participants were aware that they received the drug. No placebo was tested for comparison.

Results

• Nilotinib appears to be generally safe at low doses for people with advanced PD when taken for six months. However, one participant withdrew because of a heart attack, a known potential side effect of the drug.
• Nilotinib crosses the blood-brain barrier, meaning that it can be taken in a pill or capsule form and still reach the brain cells affected by PD.
• Analysis of participants’ cerebrospinal fluid suggested that nilotinib may have similar symptomatic, anti-PD effects in people as it did when studied in animals (for example, an increase in brain dopamine levels) but not consistently with dose. This produced side-effects that led to some participants lowering their daily dose of anti-PD medications.
• Not all study participants showed improvement in the severity of movement symptoms, but seven of the 12 did show some benefit. When all study participants were considered, the average improvement was between three to four points on a commonly used rating scale (approximately an eight percent improvement), while a five point change is generally viewed as the minimal improvement to make a difference in PD.
• Of those participants who saw beneficial changes in their PD, most saw them very soon after starting nilotinib. Typically, this indicates the drug has potential for easing symptoms (not for reversing the disease).
• Participants’ cognitive symptoms, as tested by the MMSE (Mini Mental State Exam), improved by 3.5-3.8 points in average while they were taking nilotinib, but returned to baseline after they stopped taking the medication. 
• Three months after participants stopped taking nilotinib, their movement and cognitive symptoms returned to the same levels or worse levels than those measured before the start of the clinical trial.

What Does It Mean?

In Parkinson's disease, there is an urgent need to find medications to ease cognitive symptoms and to slow or stop the disease. Since drug development and clinical trials are costly, one approach to finding new treatments more quickly is testing FDA-approved medications for other conditions to see if they also benefit people with PD. In these cases, the FDA requires rigorous studies and solid scientific evidence. With nilotinib, initial lab research seems promising, but work needs to be done to prove that it’s safe and effective in PD.

This study provides a starting basis for moving the research forward.

The primary aim of the study was to test whether nilotinib was safe to use in people with PD. While the findings show that the drug was tolerable and moderately safe; the authors also report at least one major complication of treatment, heart attack, in one of the twelve participants.

While the study was not designed to test efficacy of the drug in treating PD, the authors report initial, enticing results such as short-term improvement of motor and cognitive symptoms. Future studies should focus on a more rigorous approach with a careful eye towards proving safety and effectiveness.

• First, a significantly larger number of people with PD and DLB should be tested to better understand the drug’s safety and its effects.
• Second, scientists should randomly assign participants taking either the active drug or one that appears identical but is actually a placebo (not containing the active drug).
• Third, both the researcher and the research subject must be “blinded” to the drug or placebo assignment, meaning, neither group would know who was treated with the active drug and who was treated with a sugar pill. There is ample evidence that encouraging results in uncontrolled studies (no placebo group) may not be confirmed in larger careful controlled studies (those with a placebo group) and this would rule out this possibility.
• Lastly, the therapy should be studied for a longer duration of time. Not only is PD a chronic disease that requires long-term treatment, it is also a disease that most scientists believe would take months or years (not weeks) to slow or reverse, given the changes that occur in the brain. Thus we need to understand how the drug works over a longer period of time to see whether it’s an option in PD.

Hopefully, given that the drug is already approved by the FDA for cancer, these studies can take place promptly. It is important to note that nilotinib carries a FDA-mandated boxed warning for cardiac side effects that include sudden death. Indeed, 18 of 30 potential participants could not enter the trial because of existing cardiac conditions and one participant suffered a heart attack that may have been related to nilotinib usage.

"Overall, people with Parkinson’s and doctors alike should be excited about this novel treatment strategy, but should reserve judgement on this particular potential agent until more rigorous testing can be done," added Kathleen M. Shannon, M.D., Chair of the PDF Medical Policy Committee and Chair of Neurology at the University of Wisconsin School of Medicine and Public Health.

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