Hope in a Pill for Alzheimer's Risk Groups

Researchers are revisiting a medication designed for Alzheimer's, which might offer protection to individuals with a genetic predisposition to the disease.

In early 2023, prospects seemed grim for valiltramiprosate, known as ALZ-801, an investigational Alzheimer's treatment.

A study involving over 300 participants aged 50 or older, all genetically susceptible to Alzheimer's, initially reported no statistically significant difference between the test group and those receiving a placebo.

However, a subsequent analysis in September highlighted significant benefits for a subset of 125 individuals who only exhibited mild memory challenges at the study's onset.

Dr. Susan Abushakra of Alzheon, the company behind ALZ-801, noted that this group showed 'profound responses,' being classified with mild cognitive impairment rather than early-stage dementia.

Measured by one standard, the treatment appeared to mitigate cognitive deterioration by 52% for those with mild cognitive impairment, similar to outcomes from current Alzheimer's medications.

Determining the precise impact of ALZ-801 remains challenging due to the limited number of mild cognitive impairment participants.

More compelling data arose from observations of reduced brain shrinkage, a common symptom of Alzheimer's progression.

For instance, in the hippocampus, participants on ALZ-801 experienced about 18% less shrinkage compared to those on a placebo.

This is particularly significant as the hippocampus is a vital component of memory and cognitive processes.

The results were published in a renowned journal, supported by a substantial grant from the National Institutes of Health amounting to $47 million.

Novel Features of ALZ-801

Although typical results might not satisfy regulatory standards for FDA approval, ALZ-801 might receive special preference due to its unique advantages.

Existing treatments marketed rely on monoclonal antibodies administered intravenously, necessitating frequent hospital visits and boosting costs.

Conversely, ALZ-801 is a twice-a-day oral medication, allowing for at-home consumption.

While monoclonal antibodies focus on dismantling amyloid plaques—a hallmark of Alzheimer's formed by clumping of misfolded beta-amyloid proteins—ALZ-801 aims to prevent plaque formation altogether.

As a benefit, ALZ-801 does not typically cause the cerebral swelling or hemorrhaging associated with monoclonal antibody therapies.

An Alternative for High Genetic Risk

ALZ-801's potential as a safer option could be transformative for individuals with two copies of the APOE4 gene variant, which drastically increases Alzheimer's susceptibility.

Although these individuals only account for approximately 2% of the population, they represent about 15% of Alzheimer's cases due to their elevated risk.

Unfortunately, people with the APOE4 genotype not only face higher Alzheimer's risk but also are more likely to encounter adverse reactions from monoclonal antibody treatments.

Dr. Jessica Langbaum, an Alzheimer's expert at Banner Health, suggests that APOE4 carriers can still be treated with existing therapies, possibly by initiating treatment earlier or adjusting dosages.

However, John Watson, co-author of the research and an APOE4 gene carrier himself, advocates for a safer alternative like ALZ-801.

Watson emphasizes further that ALZ-801 may offer advantages beyond monoclonal antibodies—such as effectively lowering levels of proteins linked to neuronal death.

He states, 'Our goal is preserving neuron viability,' noting that continued ALZ-801 usage beyond initial study phases has shown sustained cognitive stability in many users in their 60s and 70s, despite genetic risks.