A is for Alzheimer's and Aducanumab

Han Yu (Kansas State University) clearly feels there are some downsides to the US Food and Drug Administration's (FDA's) approval (the first for 18 years) of Biogen's aducanumab (Aduhelm) to treat Alzheimer's disease (https://www.theguardian.com/commentisfree/2021/jun/28/alzheimers-drug-aducanumab-approval-dementia). Alzheimer's disease is a form of dementia, affecting around 30 million people world-wide. An effective drug for the treatment of this awful condition would be very happy news. Yu's concerns are consequences of the facts that the a) underlying cause(s) of Alzheimer's appear far from clear; b) FDA decision was a consequence of a rather contentious fast track scheme and c) approval of aducanumab might stop drug companies looking for alternatives to beta amyloid blockers to cure (or prevent) Alzheimer's. Yu points out that the brains of people with Alzheimer's have two obvious pathologies. Firstly, Alzheimer patients have plaques or deposits of beta amyloid between their nerve cells. This is the basis of the dominant Amyloid hypothesis, suggesting that a build up of beta amyloid causes Alzheimer's. The hypothesis has been recently modified, by assuming that beta amyloid oligomers (shorter molecules), rather than actual plaque, are the causal factor. Secondly, people with Alzheimer's dementia have fibres of Tau protein forming tangles within their nerve cells. A third suggestion (unrelated to brain pathology) is that Alzheimer sufferers have developed a metabolic disease, depriving their brains of glucose. Glucose is needed for energy but the brain relies totally on its blood supply for this material. Yu opines that there is currently no conclusive evidence to support any of these three hypotheses. Yu also notes that the FDA put aducanumab on an Accelerated Approval pathway, designed to speed up potential therapies for serious diseases. He was also informed that the FDA's advisory committee almost unanimously (on the evidence presented) voted against the approval of aducanumab. Aducanumab is a preparation of antibodies to beta amyloid. A 2015 trial, by Biogen, found it appeared to drastically reduce neural levels of beta amyloid and limited declines of cognitive and functional skills. This trial involved, however, only a total of only 165 subjects. It also didn't measure oligomers. These were assumed to have declined, because the beta amyloids were lowered. Two subsequent larger studies were initially abandoned, before one was resurrected with the claim that the highest dose of aducanumab was effective. At this point, Biogen went to the FDA for approval. Yu feels that the considerable financial rewards of the approval of aducanumab means that all companies looking for a cure for Alzheimer's, will now continue to look for anti amyloid drugs. This is in spite of the Amyloid hypothesis being far from certain. Things may be further delayed by a plan to test anti amyloids on healthy patients. It is argued that, once cognitive symptoms appear, it is probably too late to counter the neural changes. The focus here would be prevention, with 'a statin for the mind', rather developing a cure. Even better for the company, all people over a certain age would be prescribed the drug. These are all possibilities but Yu reckons it would be several years before we got definitive answers. Then, we might well have to return to our initial starting point, of not knowing the genesis of Alzheimer's.