Latest Alzheimer's Drug Fails

July 26, 2013

News Review From Harvard Medical School  --  Latest Alzheimer’s Drug Fails

In another blow to the potential treatment of Alzheimer’s disease, human testing of a drug called semagacestat has been halted. It was hoped that the drug would block gamma secretase, an enzyme that makes beta amyloid. Beta amyloid is a protein that appears to “clog” the brains of people with Alzheimer’s. The study included more than 1,500 patients with mild to moderate Alzheimer's. Those taking the test drug had a faster mental decline than people taking the placebo or fake medicine. Those on the test drug also had serious side effects. But there is a silver lining. The drug maker, Eli Lilly, made all its results public. This can help other researchers. The study appeared in the New England Journal of Medicine. Health Day News wrote about it on July 24.

By Howard LeWine, M.D.
Harvard Medical School

What Is the Doctor's Reaction?

How frustrating it must be for scientists working to find a way to stop the brain deterioration in Alzheimer’s disease. Once again, a potential treatment for which there were high expectations does not work.

Alzheimer's disease is the most common type of dementia. The main features of the disease are impaired memory and thinking. The symptoms come on gradually and get worse over time. 

The risk of developing Alzheimer's increases with age. As people live longer than ever, the numbers of people affected will increase dramatically during the next couple of decades.

The leading theory about Alzheimer's is that it begins when deposits of beta-amyloid collect around brain cells. These protein deposits gradually destroy the connections that brain cells use to receive and send information.

Scientists discovered a drug that slows this process in the brain. It’s called semagacestat.

The drug did what it was designed to do -- in animal studies. So, it was approved for human testing in people with Alzheimer’s. Half of the people in the study were given semagacestat. The other half received a placebo, a “fake” medicine with no active ingredient.

The study was stopped early. As with all human studies, independent researchers monitor the findings. These researchers are not associated with the ones running the study.

There was no improvement in memory or thinking ability in the group that took the test drug. In high doses it actually made people with Alzheimer’s less functional. And there were serious side effects.

What Changes Can I Make Now?

We have no specific treatments to prevent Alzheimer's disease and other types of dementia. While scientists keep looking, you can reduce your risk or at least delay when dementia occurs.

• Don't smoke or use other tobacco products.
• Use alcohol in moderation.
  That means no more than one drink per day for women, and no more than two per day for men.
• Maintain a healthy body weight.
  And try not to let your waist expand. People with more fat in the middle have a higher risk of developing dementia, even if their body weight is normal.
• Exercise regularly.
  Make it your goal to get at least 30 minutes of moderate-intensity exercise five days of the week.
• Keep your blood pressure in the normal range.
  Get regular exercise, eat lots of fruits and vegetables, and cut down on salt. Your doctor can prescribe medicines if needed.
• Stay socially engaged with family and friends.
• Keep your mind active.
  The scientific benefit is a bit uncertain. But even if it doesn’t help, you can have fun using your brain in activities you enjoy. For example, math games like sudoku and word games like Scrabble and Words with Friends.

There is some evidence that a Mediterranean-style diet may be especially good for the brain.

These suggestions should look familiar. They are the same ones that will help keep your heart healthy and decrease your risk of stroke.

What Can I Expect Looking to the Future?

We should applaud the drug company for releasing all of their study results to Alzheimer's Disease Cooperative Group for analysis. This group is funded U.S. National Institutes of Health.

All the data has been made public. Even though semagacestat didn’t work, scientists around the world can use the information to further Alzheimer’s research.

The drug company spent millions of dollars trying to bring semagacestat to market. Providing all of the data to everyone has set a wonderful precedent.