In a research it was shown that the Nilotinib he had been able to halt motor and non-motor (cognition and quality of life) decline in the long term. New research has identified vascular defects as the basis for the progression of Parkinson’s disease: to declare it were the scientists of the Georgetown University Medical Center.
There new discovery was explained in an article published in the scientific journal Neurology Genetics.
Nilotinib: Here’s what research confirms
Researchers claim that the Their discovery suggests that blood vessel walls called the blood brain barrier, which normally act as a crucial filter to protect the brain from toxins and to allow nutrients to pass through to nourish it, are not functioning properly in some Parkinson’s patients. because it manifests vascular defects: it prevents toxins from leaving the brain and inhibits the entry of nutrients such as glucose. Perhaps even more damaging, the dysfunctional barrier allows the body’s inflammatory cells and molecules to enter and damage the brain.
The research, the first longitudinal study to use such advanced genomics, now provides scientists with a new target for therapeutic intervention in Parkinson’s disease, said the study’s senior author. Charbel Moussa, MBBS, Ph.D., Director of Translational Neurotherapy at the Medical Center.
The new discovery comes from the second part of a Phase II clinical trial that featured the Next-generation whole genome sequencing of cerebrosponal fluid of 75 Parkinson’s patients, before and after treatment with a repurposed leukemia drug, nilotinib, or a placebo.
The research developed over a period of 27 months: the initial study was double-blind and patients were randomized to receive placebo or 150 mg or 300 mg of nilotinib for 12 months. The patients had severe Parkinson’s. All participants were treated with optimal standards of care, and many (30%) had also used the most sophisticated treatments possible, such as deep brain stimulation.
The second part of the study used an adaptive design and all participants had a 3-month drug withdrawal period before re-randomization to 150 mg or 300 mg for an additional 12 months. After 27 months, nilotinib was found to be safe and patients who received nilotinib showed a dose-dependent increase in dopamine, the chemical lost due to neuronal destruction.
“It appeared that nilotinib arrested motor and non-motor decline in patients taking the higher dose of 300 mg “, says Moussa. The clinical results of this study were published on Movement Disorders in March 2021.
The current part of the study, just published, looked at patients’ cerebrospinal fluid using theepigenomics, which is a systematic analysis of the global state of gene expression, in correlation with ongoing clinical findings. The new analysis helps explain the clinical findings.
Nilotinib inactivated a protein (DDR1) that was disrupting the blood brain barrier’s ability to function properly due to vascular defects. When DDR1 was inhibited, normal transport of molecules in and out of the brain filter was resumed, and inflammation decreased to the point that dopamine, the neurotransmitter depleted by the disease process, was again produced.
Moussa and his team have worked extensively on the effects nilotinib (Tasigna) can have on neurodegeneration, including Alzheimer’s disease and Parkinson’s disease. The drug was approved in 2007 for chronic myeloid leukemia (CML), but Moussa argued that its mechanism of action may help the brain destroy toxins that develop in the brains of patients with neurodegenerative disorders.
“Not only does nilotinib activate the system brain waste disposal to eliminate bad toxic proteins, but it also appears repair the blood brain barrier to allow these toxic wastes to leave the brain and allow nutrients to enter “explains Moussa.
“Parkinson’s disease is generally thought to involve mitochondrial or energy deficits that can be caused by environmental toxins or the buildup of toxic proteins; it has never been identified as a vascular disease, ”continued the scientist.
“To our knowledge, 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 “concluded Moussa. “Much work remains to be done, but just knowing that a patient’s cerebral vascular system is playing a significant role in disease progression is a very promising finding.“.
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