WASHINGTON – Alzheimer's patients may soon get the first skin patch to treat the creeping brain degeneration, a novel way to deliver an older drug so that it's easier to take and might even work a little better.
The patch, which infuses the drug Exelon through patients' skin, headlines a trio of innovative potential treatments unveiled Wednesday at an Alzheimer's meeting in Spain. Also under study are a prostate cancer drug that may help dementia, too, and an immune therapy to ward off the sticky gunk that is Alzheimer's brain-clogging hallmark.
The Exelon patch is furthest in the pipeline, with maker Novartis Pharmaceuticals Corp. poised to seek U.S. sales approval by year's end.
"It would be good to have an alternative" to oral medication, Dr. Bengt Winblad of Sweden's Karolinska Institute, who led the patch research, said in a telephone interview. "It's a useful approach, a new treatment strategy that would be very appreciated not only by the patients, but the caregivers."
About 4.5 million Americans have Alzheimer's, a toll expected to reach a staggering 14 million by 2050 with the graying of the population. It gradually robs sufferers of their memories and ability to care for themselves, eventually killing them.
There is no known cure or prevention; today's drugs only temporarily treat symptoms. Exelon does that by inhibiting the breakdown of a brain chemical called acetylcholine, which is vital for nerve cells to communicate with each other. The longer acetylcholine sticks around, the longer those cells can call up memories.
But it can be hard to get Alzheimer's patients to swallow pills, and Exelon can cause serious nausea and vomiting.
Applied once a day, the new skin patch sends Exelon straight into the bloodstream, bypassing the gastrointestinal tract in hopes of fewer side effects and maintaining a consistent daylong dose.
The Novartis-funded study of nearly 1,200 patients compared taking 12 milligrams of Exelon a day by mouth to a low-dose patch — equivalent to 9.5 mg of Exelon daily — or a high-dose patch, equivalent to 17.4 mg.
The low-dose patch was just as effective as the high-dose pills — but pill users suffered three times more nausea and vomiting than patch users, Winblad reported. The high-dose patch users scored slightly better on cognition tests than pill users, with similar side effects.
The patch clearly improves patients' quality of life, said Dr. Sam Gandy, director of the Farber Institute for Neurosciences at Philadelphia's Thomas Jefferson University, and an Alzheimer's Association spokesman.
"It's an important alternative in this era where we still have these symptomatic medications," Gandy said.
Far better would be drugs that could slow Alzheimer's inevitably worsening brain decay. A chief target is a sticky protein called beta-amyloid that forms clumps that coat and probably kill brain cells.
Two experimental treatments that aim to fight that plaque buildup:
—Leuprolide, an anti-hormone drug currently used to treat prostate cancer and uterine disorders.
Doctors noticed that some men with both Alzheimer's and prostate cancer seemed to fare better cognitively while taking leuprolide. If the effect was real, it was puzzling: Leuprolide blocks a hormone that in turn decreases the brain-protective sex hormones testosterone and estrogen. Then newer research suggested leuprolide had another effect, reducing beta-amyloid in mice.
Wednesday, Voyager Pharmaceutical Corp. presented initial human studies, suggesting leuprolide helped some patients maintain functional capabilities for nearly a year.
The studies tracked just 50 women and 90 men injected with either leuprolide or a dummy drug every three months plus taking regular Alzheimer's pills. And the effects weren't dramatic: 51 percent of leuprolide patients either stayed stable or showed a slight improvement, versus 35 percent of "control" patients.
Still, the drug was promising enough that Voyager is recruiting more than 500 U.S. Alzheimer's patients for advanced testing. This time, participants will receive a spaghetti strand-like implant that dissolves as the drug is absorbed.
—Antibodies, immune system cells created to soak up beta-amyloid so it can't clog the brain.
In an initial safety trial, Eli Lilly & Co. gave 19 patients a single intravenous infusion of these so-called monoclonal antibodies. Patients didn't show symptom improvement, but over the next few weeks, the beta-amyloid in their blood rose sharply, Lilly's Dr. Eric Siemers reported Wednesday. Presumably, the antibodies had sucked some of the sticky substance from the brain, sequestering it so the body could break it down.
In 2002, competitor Elan Corp. tested a vaccine designed to spur the body to create its own amyloid-clearing antibodies. That research was halted when some participants developed brain inflammation, even though others seemed to clearly improve. Now Elan and Lilly have both created their own versions of antibodies, a vaccine alternative, and begun second-stage testing.