2 New Alzheimer's Drugs Show Promise in Early Studies
Experts caution that expectations are low in field littered with drug failures
The first study tested a drug called CHF5074 that's made by an Italian company called Chiesi Pharmaceuticals. The drug is believed to turn down inflammation in the brain by modulating microglial cells.
Microglia are the housekeepers of the brain. They keep its connections free of unwanted garbage, but they also produce chemicals that trigger inflammation, which can become toxic over time.
Ninety-six patients took one of three different doses of the drug or a placebo for the first 14 weeks of the study. Then researchers opened the trial, allowing study participants who wanted to continue to keep taking their original drug dosage. Seventy-four people chose to remain on the drug. All the patients had mild cognitive impairment, an early stage of memory loss that sometimes progresses to Alzheimer's disease.
Fourteen patients dropped out of the trial early. Three left because of adverse events. The main side effect reported in the study was diarrhea, which affected 16 percent of patients on the highest dose of the drug.
After 16 months on the drug, patients who remained on the drug saw significant improvements on some tests of memory and problem solving. The drug appeared to work especially well in patients who carried a gene called APOE4, which confers the highest genetic risk for Alzheimer's. APOE4 carriers saw improvements in test scores that were about one-third to one-fourth higher than before they started the study.
"Our study shows that we may, may, in some way help patients with their memory, perhaps because we're keeping the microglia from overactivity," said study leader Dr. Joel Ross, president of the Memory Enhancement Centers of America in Eatontown, N.J.
Experts who were not involved in the research saw reasons for caution with the results.
"With  patients, you can't jump up and down about some symptoms improving in some patients," said Greg Cole, associate director of the Alzheimer's Center at the University of California, Los Angeles. "It's also not clear what the nature of the microglia modulation is exactly."
Study authors admit they don't know exactly how the drug works, either. But they said they're already planning larger studies to try to confirm their finding.
The second drug being presented at the meeting, a BACE inhibitor that's being developed by Merck, has the opposite problem. Researchers know exactly how it does what it does. They don't yet know whether it will help patients.
BACE inhibitors block an enzyme that cleaves a large protein in the brain into smaller pieces of sticky beta amyloid, a substance that forms telltale plaques in the brains of Alzheimer's patients. Blocking the enzyme blocks production of beta amyloid.
"It's been an important target. It took the drug companies at least a decade to develop this class of drugs," Rosenberg said. "Drug companies did a lot of black magic to get this drug into the brain. It's really compelling that this drug really does what it says it does."