More than 300 agents are in clinical studies for Alzheimer’s. In fact, Alzheimer’s is now the sixth most common target for new drug development. Some of the experimental agents suggest the first evidence that therapy may be able to delay the disease process. Advances in diagnosis will also be important to identify and treat Alzheimer’s at the earliest stages of the disease.
Today’s research focuses on several promising targets—beta-amyloid, tau protein and insulin resistance. Beta-amyloid is the substance that forms plaques that clog spaces between neurons. Researchers hope to identify agents that can prevent plaque formation by blocking the actions of two enzymes, called beta-secretase and gamma-secretase, which are known to play a role in plaque formation and clogging.
One promising therapy is Gammagard liquid, an intravenous drug developed to treat immune deficiency disorders. Researchers believe Gammagard may clear beta-amyloid from the brain by preventing inflammation and making the plaque less toxic. In Phase II studies, Gammagard showed promise in slowing down the progression of Alzheimer’s. Phase III trials are planned for 2013.
Tau is the protein that forms abnormal tangles inside neurons. Research is focusing on ways to prevent tau protein from twisting into tangles and destroying normal brain cell function. Two experimental agents, Rember and Davunetide, are in Phase II trials. Another possible strategy involves the way brain cells process insulin, which researchers believe may be linked to the Alzheimer’s disease process.
Other approaches include hormonal therapy, cognition enhancers, and vaccines. The hormone estrogen has positive effects on brain cells. Evista, an estrogen receptor modulator used to treat osteoporosis, is being studied in Alzheimer’s to learn if it can improve short-term memory. Two drugs aimed at improving thought processes and reasoning showed positive results in Phase II trials. Early studies show that ACC-001, and experimental Alzheimer’s vaccine, inhibited plaque accumulation in the brain, but its effects on memory and brain function are still unclear.
Recent advances in diagnosis include the use of biomarkers in cerebral spinal fluid to accurately predict how patients progress from mild symptoms to more advanced stages of Alzheimer’s. The ability to predict who will develop Alzheimer’s and how the disease will progress will be key to advancing better treatments. The first studies of a potential preventive drug, Crenezumab, are beginning in healthy people believed to be a risk for Alzheimer’s.
In the future, researchers foresee therapy that begins at the earliest stages of Alzheimer’s. Brain cell damage will be prevented or halted using a “cocktail” of medicines that work in a variety of ways to prevent damage and preserve healthy brain function.
Cowen and Company, Therapeutic Categories Outlook 2012
Toor, S. The Alzheimer’s Pipeline: What’s Next? FierceBiotech, Aug 28, 2012: