A new drug shows promise in cutting away amyloid plaque deposits in the brains of patients with mild to moderate Alzheimer's disease, according to a small, preliminary study released Monday in the Archives of Neurology.

However, the drug was linked with slight, reversible brain inflammation or fluid build-up at higher doses, and its clinical benefit is as yet unknown.

The drug, gantenerumab, is an antibody that binds to beta-amyloid, the plaque deposits in the brain thought to be responsible for Alzheimer's. From cell culture experiments performed by the researchers, they think the drug eliminates amyloid by recruiting the brain's immune system to destroy it.
In the study, 16 patients received infusions of the drug, made by Swiss pharma giant Roche, every month, for two to seven months, getting either 60-milligrams or 200-milligrams. Patients were given PET scans using the radiotracer 11-labeled Pittsburgh Compound B, which binds to beta-amyloid and fires off gamma rays picked up by the scanner to measure plaque load, before and after treatment.

At the end of the study, relative to patients getting a placebo, the PET scans showed the 60-milligram group had around 15.6 percent less amyloid build-up, and the 200-milligram group had about 35.7 percent less.

However, under MRI scans, two patients in the 200-milligram group were shown to have inflammation, fluid accumulation or microhemorrhages in areas of the greatest amyloid reduction, leading doctors to discontinue their treatment. One patient had mild symptoms -- headaches, dizziness and gait trouble -- but the problems cleared up after the treatment stopped, the researchers said.

The researchers said earlier studies on an anti-amyloid compound had found brain swelling. Also, the two patients were carriers of the APOE ε4 allele, linked in the past to greater PET-visible fluid build-up risks. The allele, found in 25 to 30 percent of the population, is found in 40 percent of those with late-onset Alzheimer's disease, according to the National Institutes of Health.

Still, while the researchers found dose-dependent reductions in amyloid levels, this didn't translate into better cognitive performance.

"[N]o consistent treatment effects on cognitive measures were noted in this small group of patients treated for a short period of time," wrote the researchers, led by Dr. Luca Santarelli with Roche. "Moreover, individual changes in cognitive measures did not correlate with changes in levels of amyloid."

Another snag: the group taking the placebo, by chance, happened to be younger and have a lower amyloid burden. The researchers tried to correct for this using statistics, but they said a planned Phase II trial, and further studies, need to be done to get a better picture of the drug's potential.

Back to HCB News

More Industry Headlines