Antitumor drug against parkinsonism and dementia
During a small Phase I clinical trial, specialists from Georgetown University Medical Center demonstrated the ability of a drug approved by the U.S. Food and Drug Administration (FDA) as a means for the treatment of chronic myeloid leukemia, to improve cognitive performance, as well as motor and non-motor disorders (for example, constipation) of the body functions of patients with Parkinson's disease and dementia with Lewy bodies. Moreover, the drug known as nilotinib (tasigna, TM Novartis) provided significant and promising changes in the levels of toxic proteins associated with disease progression (biomarkers).
During a 6-month clinical trial with an increase in the dose of nilotinib (from 150 to 300 mg per day), all patients who completed the study (11 out of 12) experienced improvement. At the same time, significant improvements in clinical indicators were observed in 10 patients. Patients also had positive changes in the concentration of biomarkers of Parkinson's disease in the cerebrospinal fluid: alpha-synuclein, beta-amyloid-40/42 and dopamine. In addition, significant changes in the total levels of Tau and p-Tau proteins were recorded. Earlier studies have shown that the levels of alpha-synuclein and beta-amyloid-40/42 in the cerebrospinal fluid decrease as Parkinson's disease worsens, while the levels of Tau and p-Tau proteins increase with the manifestation of dementia.
The researchers believe that the observed changes indicate that the brain is being cleansed of toxic proteins under the action of the drug. However, they note that the results should be interpreted with great caution, since there was no control group in the study and the effectiveness of nilotinib was not compared with the effectiveness of placebo or other drugs.
In any case, while taking nilotinib, most patients experienced an increase in dopamine production, which caused the need to reduce doses and completely discontinue the use of dopamine-boosting drugs such as L-dopa. After discontinuation of nilotinib, the decline in cognitive and motor functions intensified, despite the resumption of L-dopa therapy.
The main purpose of the study was to assess the safety of the drug. The tested dosages of nilotinib were significantly lower than the doses used in cancer therapy (up to 800 mg per day), were well tolerated and did not cause serious side effects.
In addition, the authors found that nilotinib penetrates the blood-brain barrier in larger quantities than dopamine-containing drugs.
At the same time, the visible to the naked eye effect of the drug on cognitive and motor functions in many cases was the most impressive. One of the previously wheelchair-bound patients started walking again, and the other three, who had previously lost the ability to talk, were able to maintain a dialogue. At the same time, patients with earlier stages of the disease and with diagnosed dementia with Lewy bodies, often described as a combination of Parkinson's disease and Alzheimer's disease, responded better to therapy.
The researchers are currently planning a larger clinical trial involving patients with Parkinson's disease and other neurodegenerative diseases such as Alzheimer's disease.
The results of the work were presented at the 45th Annual Congress of the Society of Neuroscientists of the USA, held on October 17-21, 2015 in Chicago.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru
22.10.2015