An Alzheimer’s pill appears to protect some in a high-risk population : Shots

Scientists are re-examining an Alzheimer’s drug that could help patients particularly at risk of developing the disease.

Jorg Greuel/Photodisc/Getty Images

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Jorg Greuel/Photodisc/Getty Images

In April, the future looked bleak for an experimental Alzheimer’s drug called valiltramiprosate, or ALZ-801.

The researchers had just published first results from a study of more than 300 people aged 50 or over, genetically predisposed to Alzheimer’s disease. Overall, those who received the drug did not perform better than those who received a placebo.

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

These participants, initially diagnosed with mild cognitive impairment rather than mild dementia, “showed very significant responses,” said Dr. Susan Abushakra, chief medical officer of Alzheon, the drug’s maker.

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

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

More robust results came from measurements of brain atrophy – the shrinkage that tends to accompany Alzheimer’s disease.

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

This is an important difference, Abushakra explains, because the hippocampus is essential for memory and thinking.

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

A different drug

Normally, such results would likely fall short of the evidence required for approval by the Food and Drug Administration.

But ALZ-801 could receive particular attention because it has potential advantages over the two drugs already on the market.

These drugs are both monoclonal antibodies administered by intravenous infusion. This increases the cost and requires patients to visit an infusion center multiple times.

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

Additionally, monoclonal antibodies work primarily by destroying sticky amyloid plaques. These plaques form after pieces of a misfolded protein called beta-amyloid begin to clump together.

Alzheon’s product is intended to prevent plaque formation by stopping amyloid proteins from clumping together.

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

Safer treatment for a 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 status means they are about 10 times more likely to develop Alzheimer’s disease. As a result, although APOE4/4 carriers only make up about 2% of the population, they make up about 15% of all people diagnosed with the disease.

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

“These people are at higher risk of brain inflammation which can be very serious,” explains Jessica LangbaumAlzheimer’s disease researcher at Banner Health in Phoenix.

Nonetheless, Langbaum believes that people with APOE4/4 genes can be safely treated with current monoclonal antibodies. This might involve starting with a lower dose, she says, or starting treatment earlier in the disease, when fewer amyloid plaques are present.

But David Watsona scientist with two copies of the APOE4 gene, believes people like him need a safer drug.

Watson, 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 appears to be better at reducing levels of a protein fragment associated with brain cell death.

“We really make a difference in keeping neurons alive,” he says.

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

Although they carry genes that typically lead to rapid decline, he says, “a lot of them hold on” into their 60s and 70s.