Treatments for Alzheimer’s Proving Elusive

Medically Reviewed by Brunilda Nazario, MD on December 13, 2016
From the WebMD Archives

Dec. 13, 2016 -- Finding a treatment to reverse or stop Alzheimer’s disease is proving elusive.

The success rate for Alzheimer’s drugs is .5%. There’s been no new drug approved in the U.S. since memantine (Namenda) in 2003. That drug aims to help symptoms such as memory problems but can't halt the long-term progression of the disease.

What's needed is a drug to attack the underlying cause of the degenerative brain disorder, says Brian Lawlor, MD, the Conolly Norman professor of old age psychiatry at Trinity College, Dublin, along with other researchers in the field. The disease affects 5 million Americans and is the sixth leading cause of death.

The Alzheimer's research community is now where cancer research was 20 or 30 years ago, Lawlor says. If someone gets a diagnosis of cancer these days, there is optimism about treatment and people ask, "What are you going to do about it?'' However, he says, ''if you get a diagnosis of Alzheimer's now, it seems like the kiss of death."

Lawlor was among 1,200 researchers and other health care professionals who gathered at an international conference to share the latest results on medications being tested for the disease.

Before the conference started, the Alzheimer’s community received more disappointing news: The drug solanezumab, which had been in final stages of testing, did not slow declines in memory and thinking. Some experts called the results "a blow." Drug maker Eli Lilly and Co., which funded the study, says it will not pursue drug approval.

Despite the setbacks, researchers say they plan to persevere.

"The [drug] trials have to go on," says Lesley Pickford, PhD, a consultant in Sebastopol, CA, involved in clinical trial design for companies. "There is a desperate need in Alzheimer's research."

Solanezumab targeted a substance in the brain called amyloid, which is found in people with the disease. No drug that treats amyloid has been a success yet. Here are some of the other potential treatments researchers discussed at the conference:

  • Aducanumab is another drug that targets amyloid. It reduced the sticky plaques better in the brains of patients who got the drug than in those who got a placebo over 54 weeks, said Samantha Budd Haeberlein, PhD, vice president of clinical development at Biogen, the drugmaker. People taking the drug also showed less decline on mental tests at 52 weeks. The company has launched phase III trials, the final phase before seeking approval, to further confirm that the drug works and is safe.
  • LMTM attacks tau protein, another substance that forms tangles in the brains of people with the disease. People with mild Alzheimer’s who took the drug did not have any difference in mental decline, compared with a placebo, after 18 months, says researcher Lon Schneider, MD, professor of psychiatry, neurology, and gerontology at the University of Southern California Keck School of Medicine. He said the drug showed some promise in a small group that took a lower dose of it without also taking other Alzheimer's drugs. Future study could focus on that regimen, Schneider says.
  • Drugs known as BACE inhibitors are another avenue. BACE stands for beta secretase cleaving enzyme, and the medications work by blocking the formation of amyloid protein. Two phase III trials of a drug known as AZD3293 are underway, with plans to enroll more than 4,000 patients, says John Sims, MD, senior medical director at Eli Lilly, which is conducting the studies with AstraZeneca. The study won't be done until 2019. (Other companies are also studying BACE inhibitors.)
  • A blood pressure medicine, nilvadipine, is under study in a European trial that includes more than 500 patients with mild to moderate Alzheimer's. Some high blood pressure medicines may have a protective role not just for stroke, but for Alzheimer's disease by reducing amyloid and decreasing inflammation, Lawlor says. The study was completed in October 2016, and results are expected by spring 2017.
  • The deterioration seen in Alzheimer's may be linked to problems in how the brain uses blood sugars and fats, similar to type 2 diabetes, says John Didsbury, PhD, the CEO of T3D Therapeutics. He is testing a drug, T3D-959, that aims to improve how the brain does these two things in 32 patients. The phase II study found improvement in thinking after 2 weeks, but the drug will need further testing.


Why the Delay?

While the development of any drug is difficult, it's even more so for Alzheimer's drugs, says James Hendrix, PhD, director of global science initiatives for the Alzheimer's Association. ''We know the drug research and development process is extremely long, expensive, and risky," he says. "From inception to delivery is about a 10- to 15-year period. ''

It's not enough to show that a medication reduces the plaques and tangles, Hendrix says. A drug also needs to improve brain health and memory in trial subjects.

Recruiting people for clinical trials for Alzheimer's medications is tougher than for other drugs, he says, because it actually requires recruiting two people -- the patient and the caregiver. Often, the caregivers are older and may be battling incapacitating conditions themselves, Hendrix says.

For many researchers, Sims says, the effort is both professional and personal. His grandmother died of Alzheimer's. Many of the researchers in the field have the same story, he says. At a recent startup meeting, those attending were asked how many had a personal connection. "About 50% of the people there raised their hand," he says.

Sims says that people fear getting Alzheimer’s more than cancer. While that fear of cancer hasn't gone away, effective treatments have improved survival for many diagnosed with it, he says.

Not the case for Alzheimer's, Sims says. "Today, no one makes it through Alzheimer's."

Schneider is on the scientific advisory board for Tau Rx.

Show Sources


Clinical Trials on Alzheimer's Disease, Dec. 8-10, San Diego, CA.

James Hendrix, PhD, director of global science initiatives, Alzheimer's Association, Chicago.

John Sims, MD, senior medical director, Eli Lilly and Co., Indianapolis.

John Didsbury, PhD, CEO, T3D Therapeutics, Research Triangle Park, NC.

Brian Lawlor, MD, Conolly Norman professor of old age psychiatry, Trinity College, Dublin.

Lon Schneider, MD, professor of psychiatry, neurology, and gerontology, University of Southern California Keck School of Medicine.

Lesley Pickford, PhD, consultant, Sebastopol, CA.

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