Alzheimer’s pills appear to protect some in high-risk populations: doses

In April, the future was looking bleak for an experimental Alzheimer’s drug called valeltramiprosate, or ALZ-801.

Researchers have just launched Top line results In a study of more than 300 people aged 50 or older who had a genetic predisposition to Alzheimer’s disease. Overall, those who got the drug did no better than those who took a placebo.

But in September, a A closer look The results revealed benefits for a subgroup of 125 people who had mild memory problems when they started taking the drug.

These participants, who were initially diagnosed with mild cognitive impairment rather than mild dementia, “showed very meaningful responses,” says Dr. Suzan Abu Chakra, chief medical officer at Alzheon, the drug’s maker.

By one measure, the drug slowed cognitive decline by 52% in people with mild cognitive impairment. This result appears to be comparable to the benefits of the two Alzheimer’s drugs now on the market: com. lecanemab and com. donabemab.

But the true effect of ALZ-801 is difficult to determine because of the relatively small number of participants in the group with mild cognitive impairment.

The most robust results came from measures of brain atrophy, the shrinkage that tends to come with Alzheimer’s disease.

In the hippocampus, for example, participants who got ALZ-801 experienced about 18% less atrophy than those who got a placebo.

Abu Shakra says this is an important difference, because the hippocampus is important for memory and thinking.

The results were published in the journal Drugs. The study was supported by a $47 million grant from the National Institutes of Health.

Different medicine

Normally, results like these would likely fall short of the evidence needed for approval by the FDA.

But ALZ-801 may be of particular interest because it has potential advantages over the two drugs already on the market.

These medications are monoclonal antibodies given intravenously. This increases cost and requires patients to make multiple trips to the infusion center.

ALZ-801 is a twice-daily tablet that can be taken at home.

Also, monoclonal antibodies work primarily by breaking down sticky amyloid plaques. These plaques form after fragments of a misfolded protein called beta-amyloid begin to clump together.

Alzheon’s product aims to prevent plaques from forming in the first place, by preventing amyloid proteins from clumping at all.

As a result, ALZ-801 does not cause swelling or bleeding in the brain that often comes with monoclonal antibody treatment.

Safer treatment for the high-risk group

The availability of a safer drug like ALZ-801 could be a boon for people who carry two copies of a gene called APOE4.

Their genetic condition means they have about 10 times the usual risk of developing Alzheimer’s disease. As a result, although APOE4/4 gene carriers make up only about 2% of the population, they represent about 15% of all people diagnosed with the disease.

Unfortunately, people with APOE4 genes are not only more likely to develop Alzheimer’s disease, they are also more likely to experience side effects from monoclonal antibody treatment.

“These individuals are more likely to develop a brain infection that can be very serious,” he says. Jessica Langbauman Alzheimer’s disease researcher at Banner Health in Phoenix.

However, Langbaum believes that people who carry APOE4/4 genes can be safely treated with current monoclonal antibodies. This may mean starting at a lower dose, or starting treatment earlier in the disease, when there are fewer amyloid plaques, she says.

but David WatsonThe scientist who carries two copies of the APOE4 gene believes people like him need safer medicine.

Watson, a co-author of the new study, also notes that ALZ may have benefits beyond those seen with monoclonal antibodies. For example, he says the experimental drug seems better at reducing levels of the part of a protein associated with brain cell death.

“We’re making a real difference in keeping neurons alive,” he says.

Watson says more evidence of the drug’s effectiveness comes from people who continued to take ALZ-801 after the initial 18-month study period ended.

Although they carry genes that normally lead to rapid decline, “many of them retain their genes” into their 60s and 70s.