Leukemia drug may benefit, Parkinson’s, Alzheimer’s disease patients
Robin Wulffson, MD
A drug that is currently used to treat leukemia has been found to slow the production of toxic proteins in the brain. These proteins have been linked to Parkinson’s disease, Alzheimer’s disease, and other forms of dementia. Researchers affiliated with Georgetown University in Washington, DC published their findings on May 10 in the journal Human Molecular Genetics.
The investigators treated mice with small doses of the drug nilotinib, which is used to treat chronic myelogenous leukemia; they found that it eliminated abnormal protein build-up in their brains. They focused on the alpha-Synuclein and tau proteins, which have been implicated in the development of Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Huntington’s disease, Lewy body dementia, and other neurodegenerative conditions. In these diseases, these proteins accumulate in brain cells and destroy them. Nilitonib works by removing these toxic proteins from brain cells.
When they began their research, the investigators were not sure whether nilitonib coldcross the blood-brain barrier. The blood–brain barrier is a separation of circulating blood from the brain extracellular fluid in the brain and spinal cord. It restricts the passage of microscopic objects such as bacteria and large molecules, while allowing the passage of small molecules such as oxygen and carbon dioxide as well as hormones and glucose. However, they found that it could pass this barrier; thus, the same form of the drug used to treat leukemia patients could be used to treat patients with neurodegenerative diseases. The only difference was that they used much lower doses of nilotinib than the amount used to treat leukemia. They estimated that humans would only need 1% of the dose typically used in chemotherapy to see neurological benefits. This finding is likely to decrease the already minimal side-effects of nilotinib, such as dizziness.
Mice treated with nilotinib experienced an improvement in cognitive (thinking) and motor functions (muscle control). In addition, they also lived longer compared to mice treated with a placebo. Thus, the investigators are optimistic that the drug will quickly enter phase two clinical trials, provided they are able to secure funding. They note that the drug is also FDA-approved to treat leukemia; it is well tolerated in humans and toxicity studies have been done. This situation is likely to speed up the approval process.
The researchers are particularly anxious to use nilotinib to treat Lewy body dementia, which is a condition in which patients develop Alzheimer’s and Parkinson’s simultaneously. Currently, there is no treatment for the disorder. Although exploring this drug as a treatment for Lewy body dementia will be the researcher’s main priority going into clinical trials, they hope to expand to clinical trials on Parkinson’s and Alzheimer’s patients as well.