Monday, February 5, 2018

Despite Setbacks, Search for Alzheimer’s Therapy Moves Forward

Treatment targeting amyloid beta—a protein that has long been assumed to cause Alzheimer’s disease (AD) through its accumulation in the brain—remains a major focus of research on potential pharmacological treatments, but drug candidates aimed at alternative pathways are catching up in development. Psychiatric News PsychoPharm has compiled a list describing some of the AD drugs in development you may hear more about in the coming year.

The most robust group of non-amyloid drugs are agents that targets tau, another protein that can form toxic aggregations in the brain. Two anti-tau monoclonal antibodies—ABBV-8E12 and RO7105705—are currently in phase 2 clinical trials, while a third BIIB092 will soon begin recruiting patients for a phase 2 trial. This class of medications has experienced its own share of failures, however; the anti-tau drug LMTM—a derivative of the chemical dye methylene blue—recently fizzled in a phase 3 study.

Among other classes of drugs, azeliragon, a small molecule that inhibits the receptor for advanced glycation end products (AGEs), is currently undergoing a phase 3 study. AGE receptors are involved in transporting amyloid beta fragments into brain cells but they are also associated with inflammation. Another agent in the pipeline is lumateperone, a molecule that targets several types of serotonin, dopamine, and glutamate receptors. Lumateperone is not a cognitive agent; rather it is being tested for the treatment of agitation in AD and other dementias.

In parallel with these trials, new tools are being developed to sharpen the picture of a brain with AD. Many recent trials rely on biomarkers from brain scans or cerebral spinal fluid samples to identify people with early stage AD; these approaches are effective but also expensive and invasive. A study published by researchers in Australia and Japan last week identified blood-based biomarkers that might identify people with prodromal AD, which could greatly speed up the recruiting process for clinical studies.

For related information, see the Psychiatric News article “Long-Term SSRI Use May Slow Progression to Alzheimer’s Dementia.”

(Image: iStock/shironosov)


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