In a new study from Georgetown University, researchers found what appears to be a big vascular defect in patients with moderately severe Parkinson’s disease.
The finding could help explain an earlier outcome of the same study, in which the drug nilotinib was able to halt motor and non-motor (cognition and quality of life) decline in the long term.
The finding suggests that blood vessel walls called the blood-brain barrier, which normally acts as a crucial filter to protect the brain against toxins as well as allow passage of nutrients to nourish it, doesn’t work correctly in some Parkinson’s patients.
It prohibits toxins from leaving the brain and inhibits nutrients such as glucose from entering.
Perhaps even more damaging, the dysfunctional barrier allows inflammatory cells and molecules from the body to enter and damage the brain.
The new discovery comes from the second part of a clinical trial that featured next-generation whole-genome sequencing of the cerebrospinal fluid of 75 Parkinson’s patients, before and after treatment with a repurposed leukemia drug, nilotinib, or a placebo.
Nilotinib was found to be safe, and patients who received nilotinib showed a dose-dependent increase of dopamine, the chemical lost as a result of neuronal destruction.
The current study examined the cerebrospinal fluid of patients via epigenomics, which is a systematic analysis of the global state of gene expression, in correlation with continuing clinical outcomes. The new analysis helps explain the clinical findings.
The team has long been working on the effects that nilotinib (Tasigna) may have on neurodegeneration, including Alzheimer’s and Parkinson’s diseases.
The drug was approved in 2007 for chronic myelogenous leukemia (CML), but Moussa reasoned that its mechanism of action may help the brain destroy toxins that develop in the brains of patients with neurodegenerative disorders.
This is the first study to show that the body’s blood-brain barrier potentially offers a target for the treatment of Parkinson’s disease.
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The study is published in Neurology Genetics. One author of the study is Charbel Moussa, MBBS, Ph.D.
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