Investigators found that the use of the leukemia drug nilotinib in mice specially bred to over express alpha-synuclein and tau was successful in eliminating the abnormal accumulations of these proteins. They also found that cognition (thinking) as well as movement and functional skills were also greatly improved by the use of this drug in these mice. And the mice actually lived longer than the untreated mice. Alpha-synuclein and tau proteins are the main causes of Lewy Body dementia in Parkinson’s and other neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s and Huntington’s. It is an excess of these abnormal proteins that cause brain cells to deteriorate and be destroyed.
The investigators in this group had been searching to find a drug that could cross the blood-brain barrier in order to destroy cancerous tumor cells in the brain. Nilotinib was one drug that had that ability. When used in much higher concentrations to treat chronic myelogenous leukemia, the drug forces cancer cells to turn on themselves and totally self destruct. The researchers reasoned that very small doses might be sufficient to rid brain cells of only the malfunctioning proteins. Nothing like this had ever been done before.
The research group from Georgetown University is led by senior researcher Charbel E-H Moussa, M.B., Ph.D. He says “This drug, in very low doses, turns on the garbage disposal machinery inside neurons to clear toxic proteins from the cell.” Dr. Moussa also said “We successfully tested this for several disease models that have an accumulation of intracellular protein. It gets rid of alpha synuclein and tau in a number of movement disorders, such as Parkinson’s disease as well as Lew body dementia.” Dr. Moussa feels that for this treatment to be most effective, it would need to be used early in the neurodegenerative disease.
He is currently planning a phase II clinical trial in patients who have already been diagnosed with alpha synuclein inclusions such as Lewy Body dementia and Parkinson’s. He notes that the drug already had FDA approval for leukemia and it is well tolerated in humans. Hopefully, this will help to this clinical trial sooner rather than later. The researchers are very optimistic and eager to proceed with this trial.