Is Aducanumab an Alzheimer’s disease modifying Drug?

The answer depends on who you ask the question. The FDA thinks it is and granted an ‘accelerated approval’ of the drug despite poor clinical trial data. Aduhelm, the formal name for Aducanumab clears poorly the accumulation of beta-amyloid protein from the brain. Accumulation of this protein is associated with Alzheimer’s disease (AD). However, clinical trials of the drug failed to show any significant slowing down of the actual symptoms of AD. The mechanistic action of the drugs for Alzheimer’s that failed in the past and the design of the class of drugs that includes Aduhelm are based on a misconception: removing the amyloid would ameliorate AD symptoms. Unfortunately, that line of thinking is completely incorrect and the various amyloid removing drugs—including donanemab, solanezumab, bapineuzumab, and now Aducanumab— actually supported the misconception because even though the amyloid got reduced in most cases, cognition was not improved. In short, Aducanumab is more of an amyloid-reducing drug and less of an Alzheimer’s disease-modifying drug.

A disease-modifying and not an amyloid-reducing drug is needed to delay or reverse AD. And the reason is clear as indicated in the Table below: While the item in red in the Table indicates the target of preference for most of the pharma and biotech companies, genetic and biochemical research studies have revealed an extensive network of molecular interactions involved in the development of AD. These include, in addition to amyloid, the gut microbiome, inflammatory mediators, apolipoproteins, vitamins, minerals, metabolic factors, hormonal mediators, trophic molecules, neuromodulators, and a host of other potential targets.

Thus, addressing multiple targets underlying the AD pathophysiology may be a more sensible approach; in other words, the effects of the various targets may be additive or even synergistic suggesting that a network-based therapeutics approach, rather than a single target-based approach, may be more effective for the treatment of AD. As the well-known Systems Biologist Dr Leroy Hood pointed out in his Op-Ed: The key to AD treatment or prevention is not a single drug but a ‘multi-therapeutic’ program that addresses all the confounding factors (as shown in the Table) through interventions including but not limited to personalized diet, physical exercise, brain training, detoxification, and sleep. The successful results from recent clinical trials using multi-therapeutic programs are a testimony to the effectiveness of such systems-based therapies.

Based on this premise, we at Apollo Health have launched a multi-therapeutic program that involves a personalized, precision treatment using strategies focused on nutrition, exercise, sleep, stress, brain stimulation, detoxification, and supplementation—to provide optimal conditions for the brain to thrive. This treatment methodology is the future—based on systems-medicine and is akin to repairing a roof with numerous holes: the more holes you cover, the more success you have at fixing the problem. Data mining of the large data sets will help us to continue to optimize the overall protocol and to keep improving the outcomes for the many patients in need.