Scientists have identified a new drug that is effective at inhibiting the development of plaques, a key sign of Alzheimer’s disease, in the brains of animals.
The research, which appears in the Journal of Experimental Medicine, lays the groundwork for further studies. If these corroborate the findings, they could pave the way for clinical trials in humans.
Alzheimer’s is a developmental neurodegenerative disease that typically occurs in people aged 60 or older.
In 2014, about 5 million people in the U.S. had Alzheimer’s disease. By 2060, this figure will increase to around 14 million, the Centers for Disease Control and Prevention (CDC) estimate. Alzheimer’s is currently one of the top 10 leading causes of death in the U.S.
As the National Institute on Aging note, the disease typically begins with milder symptoms, such as memory loss and confusion. A person with severe Alzheimer’s may not recognize close family members or friends and be unable to communicate.
Scientists are not yet sure why some people, and not others, develop Alzheimer’s disease. Experts believe that it results from a characteristic buildup of protein plaques in the brain. These plaques then affect the functioning of brain cells, which causes slow cognitive decline.
The plaques can appear a decade before the person experiences symptoms.
Currently, there is no cure for Alzheimer’s disease. Treatments address symptoms without tackling the root cause.
Modulation or inhibition?
The team behind the recent study identified and tested a new drug that appears to be safe and effective at reducing the buildup of plaques in animal models of the disease.
Prof. Steven Wagner, of the Department of Neurosciences at the University of California San Diego School of Medicine, notes, “Alzheimer’s disease is an extraordinarily complex and multifaceted condition that has, so far, defied effective treatment, let alone prevention.”
“Our findings suggest a potential therapy that might prevent one of the key elements of Alzheimer’s disease,” Prof. Wagner, also the study’s senior author, explains.
The therapy works by modulating an enzyme called gamma-secretase, which is key to the production of plaques in the brain of a person with Alzheimer’s.
In previous research, scientists inhibited gamma-secretase. However, this yielded significant adverse effects, including the “worsening of cognitive abilities relative to placebo,” according to Prof. Wagner and his co-authors.
In the recent study, the team tried a slightly different approach. They used a gamma-secretase modulator (GSM), a drug that adjusts rather than inhibits the action of the enzyme.
This allowed gamma-secretase to continue fulfilling its other important roles but reduced its contribution to the buildup of plaques.
Safe and effective in animals
After testing the GSM in mice, rats, and macaques, the researchers found that it significantly reduced the buildup of peptides that create plaques. Also, the drug produced no toxic side effects in any animals.
Administering the GSM before or after the animals began to develop plaques reduced overall plaque formation. It also reduced inflammation associated with plaque buildup — which is key because scientists believe that this inflammation plays a role in the disease’s progression.
The researchers hope that, eventually, the GSM might become a therapy that can inhibit the development of Alzheimer’s disease in humans.
According to study co-author Prof. Rudolph Tanzi, director of the Genetics and Aging Research Unit at Massachusetts General Hospital, in Boston, “In this study, we have pharmacologically characterized a potent GSM that, based on its preclinical attributes, appears to equal or exceed the potency of any previously tested GSMs.” He continues:
“Future clinical trials will determine whether this promising GSM is safe in humans and could be used to effectively treat or prevent Alzheimer’s disease.”