We may be getting close.
The ultimate goal: to identify people at risk early and give them a safe medication that would prevent serious symptoms altogether. This may require a combination of medications, as we’re seeing now for many cancers and HIV.
So far, the field is strewn with drugs that failed in clinical trials. The five drugs that have come into use — Aricept and Namenda are the best known — only temporarily affect symptoms. But researchers have identified several lines of attack, through decades of basic research on the characteristics of Alzheimer’s patients.
You may have heard that people with Alzheimer’s have plaques on the brain analogous to plaque gumming up the arteries in heart disease. The main component of these brain plaques is a protein fragment called beta-amyloid. The Eli Lilly drug solanezumab, which the company first began to develop in 2004, targeted these plaques, but has now failed three times in large-scale human trials after billions in research costs. But other attacks may work. Another drug under development — Merck’s verubecestate — takes an upstream approach, reducing the activity of an enzyme that leads to the production of beta-amyloid. Merck is testing it in more than 2,000 people with mild-to-moderate Alzheimer’s, and in 1,500 individuals who are seeing the very first signs of memory loss but functioning normally. Merck is slated to present results in June 2017.
In 2018, Biogen may disclose late-stage data on its strategy against beta-amyloid. Its drug is a Wall Street favorite based on early studies that showed significant reduction in cognitive decline in early-stage patients.
Researchers also have their eye on abnormal forms of tau protein, which can cause tangles in neurons that show up in Alzheimer’s patients. Normally, tau protein helps structure neurons. Some studies suggest that high tau is more closely related to the onset of symptoms than high amyloid.
A vaccine called AADvac1 aims to stimulate the body to attack those abnormal tau proteins. An early trial should be completed in February 2019.
Both beta-amyloid plaques and tau tangles cause an immune response in the brain, which leads to inflammation: your body perceives an enemy but its response creates your symptoms and does not successfully fight the cause.
CSP-1103 (also known as CHF 5074) focuses on reducing that inflammation. Early results with people showing early memory problems found that it helped their symptoms after 16 months of treatment, and prevented amyloid plaques.
A drug called Intepirdine boosts acetylcholine, a brain chemical that is low in Alzheimer’s patients and helps nerve cells in the brain communicate.
Alzheimer’s runs in families, so another approach is to identify and treat people without symptoms who carry genes that increase their risk. One trial is testing whether the anti-diabetes drug pioglitazone, which may decrease inflammation and beta-amyloid brain levels, can protect these volunteers.
Altogether, there’s reason for Alzheimer’s patients and their families to have hope.
February 07, 2017
Christopher Nystuen, MD, MBA