Failed Alzheimer's Disease Drug Trial May Be Caused By A Second Underlying Disease

There have already been a number of drug trials intended to test drug to potentially cure Alzheimer's disease. However, until now, several drug trials have failed, and scientists may have recently found the reason for these failed trials. A study revealed that these failures can be traced back to patients having other underlying diseases.

Alzheimer's disease (AD) is the leading cause of dementia and many people use the two terms interchangeably. However, the inadequate blood flow to the brain due to microinfarcts, mini-strokes, or strokes is a hallmark sign of a disease called Vascular Cognitive Impairment and Dementia (VCID). VCID is the second most common cause of dementia, and the two are not mutually restricted, researchers found that at least 40-60 percent of Alzheimer's disease patients also have VCID.

According to UPI, a paper recently published in the Journal of Neuroscience by Donna Wilcock, Ph.D., of the University of Kentucky Sanders-Brown Center on Aging, reports that a specific form of immunotherapy targeted to Alzheimer's patients may be ineffective when that patient is also suffering from VCID.

"These findings are important in that they provide a possible explanation for why clinical trials of anti-Aβ immunotherapy for Alzheimer's disease have been historically unsuccessful," Wilcock said. "If up to 40 percent of people with Alzheimer's also have VCID, treatment candidates that target only the AD physiology won't be effective in those patients. It's like treating only half the disease," reported Medical Xpress. Reports also said that most researchers agree that brain plaques formation that contains amyloid β (Aβ) peptides is the first step in the development of AD, which has led to a race to identify and test different treatments that may lower the levels of these plaques.

Anti-Aβ immunotherapy, which utilizes antibodies to against A to clear it from the brain, has been found to lead the hunt. However, while these drugs showed a potential cure in animal studies, clinical trials have failed to show the same benefits in human patients. "There has been one failure after another in clinical trials, which has been really disheartening for the scientific community and for patients, Wilcock said. "My work might shed some early light on why they failed and eventually open the door for a combination treatment for VCID and AD."

However, uknow.uky.edu reported that without a relevant animal model, it would not have been possible for the researchers to test the hypothesis. Thankfully, Wilcock and her team had already created an ingenious model which is a combination of AD and VCID.  With the help of a mouse model, together with its original model of AD without VCID, Wilcock analyzed the ability of an anti-Aβ antibody to improve cognitive abilities in both models.

The research team found that although Aβ levels decreased in both groups, cognitive function was not improved in the groups with combined AD and VCID. "The failure of anti-Aβ immunotherapy in the mixed AD-VCID model suggests that both disease processes have to be treated to have a successful outcome," Wilcock said. "The missing link has been that our animal models usually possess the hallmarks of only one disease, which has led to a failure of successful translation to clinic."

Wilcock also said that developing a model that can more accurately show the brain changes researchers can see in the human brain with dementia, they will be able to better develop their treatment approaches and increase their chances of successfully translating better results. "Our next step is to add a treatment for VCID on top of the Aβ immunotherapy to try to overcome the inability to produce a meaningful improvement in learning and memory," she added.