Progress on Parkinson’s
By Alexis Stefano, Behavioral Neuroscience, 2017
At first glance, Parkinson’s disease and Chronic Myelogenous leukemia (CML) seem to have nothing in common. One is a neurodegenerative disease that causes a patient to experience tremors and loss of cognitive function, while the other is a slow moving blood and bone cancer. Parkinson’s causes a loss of cells, specifically dopamine neurons, and CML causes a proliferation of malformed white blood cells. Upon closer examination, however, it is easy to see the similarities between these two diseases. Both diseases are most commonly found in patients older than 60. Both result from various genetic mutations that can lead to a buildup of proteins, due to a malfunctioning version of the enzyme tyrosine kinase. Tyrosine kinase plays many roles in the cell, and mainly acts as an “on/off” switch for regulating cell functions.
The difference between diseases is the way dopamine neurons react to the actions of tyrosine kinase, compared to myeloid stem cells. Myeloid stem cells are the precursors to white blood cells (specifically granulocytes), red blood cells, and platelets. When these kinds of stem cells have too much tyrosine kinase activity, more of them become granulocytes than normal. However, these extra granulocytes are abnormal and take up the place of healthy white blood cells in the blood, causing susceptibility to infection and anemia. On the other hand, tyrosine kinase activity in dopamine neurons causes buildup of proteins, known as parkin substrates. This buildup of proteins in the cell leads to oxidative stress and cell death. In some ways, the differences between these two diseases are also their similarities. Because the root cause of these malfunctions lead back to the same protein, it is possible that targeted therapies may work for both disorders.
This was exactly the thinking of the scientists who decided to test the efficacy of the CML drug Nilotinib on Parkinson’s disease. Nilotinib is a drug that inhibits the gene coding for the malfunctioning tyrosine kinase. It was previously used as a targeted treatment for CML patients. Luckily, Nilotinib was known to be able to cross the blood brain barrier, and would be able to reach the dying dopamine neurons in Parkinson’s patients. Scientists who completed a pre-clinical trial found that Nilotinib was effective in reducing the activation of the gene for tyrosine kinase and reducing the parkin substrates that were clogging up the dopamine neurons in an animal model of Parkinson’s disease. This created a protective effect that prevented the progression of neuronal cell death and could potentially prevent the progression of Parkinson’s disease.
In a recent clinical trial of Nilotinib as a treatment for Parkinson’s disease, all 11 patients who completed the trial had extreme improvements in function. The results of the trial were reported at the annual meeting of the Society for Neuroscience in October. According to the report, the drug improved cognitive test scores, allowed patients to feed themselves, and also allowed them to stop using walkers. Three patients regained the ability to speak. There was a significant decrease in tremors and freezing behavior in the patients. Further tests on the patients revealed evidence that the remaining dopamine neurons in their brains were functioning better.
This allowed the patients to be on lower doses of their regular medications, which help reduce the symptoms of Parkinson’s disease. Although this seems like an amazing victory, more clinical studies must be done to confirm the results before Nilotinib can become widely prescribed for Parkinson’s patients. The clinical study that just completed did not include any patients taking a placebo, and therefore cannot officially confirm that the improvements were due to the drug itself and not a placebo effect. Another caveat of the Nilotinib progress is that it is extremely expensive. Leukemia patients currently taking Nilotinib pay thousands of dollars a month for their treatments.