Alzheimer's - What is a Cure?

A disease which at its very core erases the sufferers individuality, Alzheimer's disease is a frightening and not fully understood pathology. There have been various hypotheses about the cause of the disease with most experts accepting the protein misfolding theory. There are some other interesting theories but for now the protein theory reigns.

The FDA's approval of Aducanumab for the treatment of Alzheimer's has been a controversial one. They approved the antibody disregarding the findings of the independent panel of experts which advise on such approvals. The cost of the new therapy in comparison to the purported benefits has been questioned. One of the leading member of the FDA advisory team, who is also an expert in the field resigned in protest. All these led me to ask the most basic question - What is a cure in case of Alzheimer's?

The pathophysiology of the disease is well characterized only in a sense that we know there are clumps of misfolded proteins in the brains of the sufferers. These misfolded tau proteins are also seen in some other neurodegenerative diseases. Tau proteins role has traditionally been thought of as a scaffold. Certain genetic conditions predispose to early onset Alzheimer's disease and familial clusters have been identified (https://pubmed.ncbi.nlm.nih.gov/1671712/). Individuals with Down's syndrome also have an early onset of Alzheimer's disease as the gene for amyloid precursor protein (APP) is on chromosome 21. The end result of this process is in simple terms - a loss of memory and individuality and a slow descent into the abyss. Still Alice, a 2014 movie based on the real life of a linguistics professor and the Anthony Hopkins starrer The Father released in 2020, are poignant depictions of the sufferings endured by patients of Alzheimer's disease.

Cure then for these patients is not just the removal of tau proteins - the mechanisms of the antibody based drugs - but a functional improvement in their lives. And herein lies the problem. Misfolded tau proteins are the end result of a chronic long ongoing process. Whether removal of these misfolded proteins will reverse the damage to the brain is yet to be proven conclusively. But for a disease for which no treatment exists, any innovation however small its benefit deserves to be studied and most importantly, tried. The monoclonal antibodies - Aducanumab is just the first of its class, there are at least four more in the pipeline - are the first class of drugs which have shown potential to interfere with the pathological markers. They may not offer significant functional improvement, for the simple reason that by the time they are deployed the damage done to the brain would be way beyond what these drugs can salvage. And salvaging is what needs to be done. A class of drugs which would halt the misfolding of tau and thus prevent the disease itself is the end goal, but till such time whatever small incremental developments occur should be enthusiastically harnessed.

With every new drug the expectations of the society are reset to a higher level. When sulfanilamide and penicillin were introduced they were proclaimed as the true miracle drugs. For the past few decades what we have had are drugs that offer small incremental benefits. And it is expected that it will be so in the coming few years.

Neurodegenerative diseases are challenging because we still understand so little about them. What our patients need is a strong social support system coupled with the judicious use of the newer drugs. We all want miracles, but seldom do miracles occur.