There’s no disguising the fact that once-promising drugs for treating Alzheimer’s and other forms of dementia, which together affect 5 million people in the U.S., have fizzled pretty dismally in recent months. According to MSN Money, 150 different companies are working on Alzheimer’s drugs, and recent disappointments in several of the drugs’ efficacy have some companies beginning to wonder if the research is cost-effective (the article goes on to outline some of the bigger clinical trial failures in the last couple of years). A new study from Georgetown University Medical Center, however, offers an interesting approach to dementia treatment: It uses low does of a cancer drug to induce the aberrant brain cells to devour their own insides, thereby preventing the gunky plaques and tangles of dementia from aggregating.
The team, led by Charbel E-H Moussa, wanted to determine whether a drug that forces cancerous cells to self-destruct by destroying their own organelles might do the same in a slightly different type of scenario – dementia. The first challenge was to find a cancer drug that crosses the blood-brain-barrier, a requisite, of course, for applying it to the malfunctioning neurons in dementia. They found that nilotinib and bosutinib, both used to treat forms of leukemia, fit the bill.
The team used a mouse model, in which the brain develops a buildup of a protein called alpha-Synuclein, which is found in a number of neurodegenerative diseases. “We successfully tested [nilotinib] for several diseases models that have an accumulation of intracellular protein,” Moussa says. “It gets rid of alpha synuclein and tau in a number of movement disorders, such as Parkinson’s disease as well as Lewy body dementia.”
They found that administering 1 milligram of the drug to the animals every other day cleared out the debris from their brains, and led to improvements in movement and overall functionality, compared to control mice who did not receive the treatment.
“This drug, in very low doses, turns on the garbage disposal machinery inside neurons to clear toxic proteins from the cell,” said E-H Moussa. “By clearing intracellular proteins, the drug prevents their accumulation in pathological inclusions called Lewy bodies and/or tangles, and also prevents amyloid secretion into the extracellular space between neurons, so proteins do not form toxic clumps or plaques in the brain.” Though there are still many details that are poorly understood in dementia, it seems that the accumulation of various proteins inside the cell, as well as their clearance or expulsion to the outside of the cell, both play a role in the progression of dementia.
If effective, the researchers say, the drug/s could help treat the brain pathology associated with neurodegenerative diseases including Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), frontotemporal degeneration (FTD), Huntington disease, and Lewy body dementia (LBD).
Plans are currently underway for phase II clinical trials, for use in people with Lewy body dementia, Parkinson’s disease, progressive supranuclear palsy (PSP) and multiple system atrophy (MSA).
The researchers are hopeful. Says Moussa,”No one has tried anything like this before.”