One former ASU professor and his colleagues are tackling the effects of Alzheimer's disease with an anti-cancer drug and over $4 million in research grants.
Boris DeCourt, a former assistant research professor at the ASU-Banner Neurodegenerative Disease Research Center, is looking to tackle the disease by utilizing the cancer drug lenalidomide to reduce inflammation in the brain. He is currently working at the Cleveland Clinic Nevada.
Alzheimer’s is a degenerative disease of the brain that affects 5.7 million Americans, according to the Alzheimer’s Association, and while there is no discovered cure, researchers are hard at work to find one.
The initial idea sprung more than 10 years ago when DeCourt worked at the Banner Sun Health Research Institute. DeCourt said that during the course of Alzheimer’s, one's brain will experience inflammation.
According to the Alzheimer’s Drug Discovery Foundation, inflammation of the brain is a common occurrence in patients with Alzheimer’s, but the role it plays in the progression of the disease is unknown.
“The question that we asked is 'How can we can decrease inflammation in the brain for these patients?'” he said. “A lot of different drugs have been checked and looked at, and we know, for example, aspirin or Tylenol doesn't work enough for Alzheimer's.”
This led him to explore using thalidomide, an immunomodulatory agent used to treat blood cancers such as multiple myeloma. For a few years, he ran a clinical trial with the drug but found that patients weren’t responding well to it due to its toxicity, he said.
Instead, he looked at lenalidomide, which has a similar effect without the toxicity of thalidomide, which he said allows him to give his patients higher doses.
DeCourt currently has two trials for this test: one is funded by the National Institute of Health for $3.2 million, and the other, funded by $1.3 million from the ADDF, making for a combined 75 patients to undergo the trials.
Even though the trials are organized similarly, they focus on different aspects of Alzheimer's and are expected to last a total of 18 months, DeCourt said.
“The clinical trial from the NIH will be a lot more oriented toward cognitive improvement or lack of clinical decline to be more precise,” he said. “Whereas the clinical trial for the ADDF, we focus really much more on markers of inflammation.”
The NIH trial is in its early stages but was put on hold due to the government shutdown. DeCourt said the trial is in the process of randomizing which patients will receive a placebo and which will not. Additionally, he is awaiting the FDA’s approval of his particular use of lenalidomide.
DeCourt continues to work on the trial with several ASU colleagues, including bio-statistic expert Jeffrey Wilson, an associate professor in the department of economics and co-director of the biostatistics core in the NIH Center for Alzheimer's at ASU. The duo have worked together for over 10 years.
Wilson is in charge of reviewing the results and is also the only person aside from a patient’s pharmacist to know which patient has received a placebo.
“If I notice that a statistical difference between the placebo and those who got the treatment, then I would say that the treatment made a difference and we could then move to the other stages,” he said.
Diego Mastroeni, assistant research professor at the School of Life Sciences and the Biodesign Neurodegenerative Disease Research Center, said brain inflammation is also common in diseases such as Huntington’s disease, dementia and Parkinson’s disease.
He said that if lenalidomide works well in Alzheimer’s patients, it may have applications in other diseases.
Mastroeni, who is not working in this particular trial, said that in Alzheimer’s, plaque in the brain will activate the microglia, which are a group of cells that “clean all the garbage up in our brain."
“There's so much of this pathology that the cells become activated and in doing so they activate neighboring cells,” he said. “So all the cells are releasing inflammatory signals that something's going on, we're trying to clean things up, but there's just so much of it.”
In addition to his two clinical trials, DeCourt has a pre-clinical trial with ASU that involves testing lenalidomide on transgenic mice. If all goes well, DeCourt said that he will perform a larger test with 200 to 300 patients. If successful, he will go to the FDA to show the successes are reproducible.
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