This summer, two drugs under development for Alzheimer’s disease were declared failures, ruining the chances of finding a near-term fix for an illness that is ravaging the memories of more than 5 million Americans.
But scientists and Boston-area executives say they are still optimistic that drugs, some of which are already under development, eventually will treat Alzheimer’s effectively and even prevent it from attacking many of the 13 million people projected to have the fatal disease by 2050.
The question is how soon that will happen, rather than than when, said Dr. Norman Relkin, director of the Memory Disorders Program at NY-Presbyterian/Weill Cornell Medical Center.
We are in a gap period, he and others said, between what researchers understand about the disease and what they have had time to show in patient trials.
Several Alzheimer’s specialists, including Relkin, expressed concern that failure of the two monoclonal antibody drugs would discourage pharmaceutical companies from investing in new drugs to fightthe disease. Others see no chance companies will give up on the potential to find blockbuster treatments.
“I think the people who really understand Alzheimer’s, even the companies that just had these failures, are still committed to the area,” said Jeff Ives, chief executive of Satori Pharmaceuticals of Cambridge. “In Western diseases, I don’t know of anything that’s a better opportunity.”
A drug that effectively prevented Alzheimer’s might need to be taken for years, if not decades, he said, promising huge returns for drug companies.
Most Alzheimer’s researchers now believe the disease is initiated by the buildup of a sticky protein called beta amyloid or Aβ (pronounced A-beta). Eventually, an accumulation of Aβ chokes off nerve cells, leading to cell death.
The two failed drugs, solanezumab and bapineuzumab, were intended to stick to Aβ and either neutralize it or flush much of it out of the brain.
It is not clear yet whether they did not succeed in patients because the drugs did not do their job well, or because they were tried too late in the course of the disease. Neither drug can resuscitate dead brain cells, but they may be able to stop or slow the disease’s progression if started earlier, researchers said.
The trials “strongly suggested that we’re treating this disease too late,” said Dr. Dennis J. Selkoe, a professor of neurology at Harvard Medical School and Brigham and Women’s Hospital. “We need to move earlier.”
Other recent research into the genetic form of Alzheimer’s indicates the disease may begin 25 years before its hallmark memory loss is evident.
Selkoe’s colleague, Dr. Reisa Sperling, will present more data from the trial of bapineuzumab Tuesday, at a conference in Stockholm. The additional data, plus more details to be released about solanezumab, made by Eli Lilly and Co., at a Boston conference next month, may support the drugs’ overall approach, said Selkoe, who is a board member of Elan Corp., which developed bapineuzumab along with Johnson & Johnson and Pfizer Inc.
Other drugs are aimed at eliminating Aβ earlier, before it is cut out of a longer protein called the amyloid precursor protein. Some drugs – called beta and gamma secretase inhibitors – block these cuts, and therefore the formation of Aβ. Satori Pharmaceuticals is developing a drug that tries to modulate, rather than eliminate production of Aβ via gamma secretase, which Ives said makes it safer than previous inhibitors.
Yet another drug, developed by Prana Biotechnology Ltd., which was formed in Boston and is now headquartered in Australia, keeps the metals zinc and copper from sticking to Aβ, neutralizing its toxic effects and allowing the body to better get rid of the protein, said Dr. Rudolph Tanzi, a professor of neurology at Harvard Medical School and Massachusetts General Hospital, and Prana cofounder.
Relkin is leading late-stage clinical trials in a drug called Gammagard IVIg, which appears to reduce the brain degeneration associated with Alzheimer’s.
It’s also crucial to develop medications for patients whose disease is too advanced to be helped by these drugs, said Dr. Jeffrey Cummings, director of the Cleveland Clinic Lou Ruvo Center for Brain Health.
Current treatments can mitigate some symptoms, such as memory problems, aggression, and wandering — but only a little.
“The patient may get somewhat better or decline may be delayed, but they’re certainly not restored to normal,” Cummings said. “So we need more symptomatic drugs and more powerful symptomatic drugs.”
Cummings, who said he is involved with about 20 Alzheimer’s drug development companies, said he’s particularly optimistic about one being developed by EnVivo Pharmaceuticals, of Watertown. In July, EnVivo published midstage trial results showing that its drug EVP-6124 can improve some measures of memory and personal care.
The drug is designed to improve signaling among brain cells involved in learning and memory, according to Dr. Joseph T. Coyle, a professor of psychiatry and neuroscience at Harvard Medical School and McLean Hospital in Belmont, who also sits on EnVivo’s advisory board.
Its benefits, however will probably be short-lived.
“It may turn the clock back six months or so in terms of cognitive decline, but ultimately it doesn’t affect the underlying pathology” of the disease, Coyle said.
Correction: Because of a reporting error, the name of the director of the Cleveland Clinic Lou Ruvo Center for Brain Health was incorrect in an earlier version of this story. He is Dr. Jeffrey Cummings.