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Parkinson’s symptoms blocked in mice

By Tim Sandle     Jul 6, 2016 in Science
Scientists, blocking an enzyme, have been able to block the symptoms of Parkinson’s disease. This is not a cure, but it could be the basis for managed treatment program.
Parkinson’s disease is a degenerative disorder of the central nervous system mainly affecting the motor system. The first wave of symptoms includes shaking, rigidity, slowness of movement and difficulty with walking and gait. These symptoms are manifest progressively (that is, they get worse over time.) Following this, behavioural and cognitive problems can arise.
There is no known cause for Parkinson’s disease, although it is thought to be either genetic or due to toxins. Neither is there a cure. Most research efforts are focused on addressing the symptoms. This is the reason for the current research into enzyme blocking.
The enzyme that, when blocked, triggers the beneficial effect is called c-Abl. This was shown using laboratory mice in controlled experiments. The research team found that a drug, commonly used to treat leukemia, has the ability to inhibit the c-Abl enzyme. The drug is called nilotinib. The drug is a type of small-molecule tyrosine kinase inhibitor.
With the study, the scientists knocked out the gene for c-Abl in genetically engineered mice. The mice had been engineered to have Parkinson’s disease. When the gene was disabled, the symptoms reduced. In addition, when the activity of the enzyme was increased, the Parkinson’s like symptoms worsened. In a secondary experiment, when mice not engineered to have Parkinson’s disease also had an increase in the enzyme activity, they began to develop symptoms of the neurodegenerative disease. The totality of the research findings, therefore, points towards c-Abl.
Scientifically the reason for this is thought to be the association between c-Abl and a protein called α-synuclein, which is found in the brain. The clumping of α-synuclein is associated with Parkinon’s disease.
The results have only been confirmed using mice and considerably more research is required before human trials could take place. Here the results seen with the mice may not occur with human subjects (although the research team are hopeful.)
The study was carried out at the Johns Hopkins University School of Medicine and led by Dr.
Ted Dawson. Speaking with BioScience Technology, Dr. Dawson said: “We plan to look into whether α-synuclein with a phosphate group on the spot c-Abl targets could serve as a measure of Parkinson’s disease severity.”
Inspired by the news, Cure Parkinson's (@CureParkinsonsT) tweeted: "This already available c-Abl drug shows promise in treating the symptoms of #Parkinsons."
The research is published in The Journal of Clinical Investigation. The paper is titled “Activation of tyrosine kinase c-Abl contributes to α-synuclein–induced neurodegeneration.”
More about Parkinson's Disease, Neurodegenrative disease, Clinical trial
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