Aducanumab, marketed under the name “Aduhelm”, is an anti-amyloid monoclonal antibody, the latest in a series of such drugs, used for testing against Alzheimer’s disease.In the past few decades, billions of dollars have been used to target amyloids that clump together to form neuritic plaques Alois Alzheimer In 1906.Such drugs reduce the accumulation of amyloid; however, since 2000, a virtual 100% failure rate In clinical trials, some therapies actually deterioration Patient results.
In 2019, Adukazumab Failure In the null analysis of two combined phase III randomized controlled trials, but Later Claimed to have little benefit to some patients in the high-dose group. The accelerated approval of this biologic from the FDA is not based on its clinical benefits, but on its ability to reduce amyloid in PET scans.Biogen immediately priced this therapy at US$56,000 per year, making it possible The most expensive medicine In the history of this country.
This dilemma is more surreal, because in the absence of more conclusive evidence, there is not enough evidence that the drug is actually clinically beneficial to people who take it. Aducanumab is injected intravenously Observed It resulted in 40% of high-dose participants with brain swelling or bleeding, and a higher incidence of headaches, falls, and diarrhea. FDA’s decision is facing Recommendations close to consensus From its advisory board no approve.Since then, the three members of the committee Resign; Several federations survey Has been activated to examine the close relationship between Biogen and the FDA; and Department of Veterans Affairs Many private insurance companies and well-known hospital systems have transmit signal They don’t want to have anything to do with drugs. At the same time, Biogen launched the “it’s time,” asked potential consumers about their memory loss, and finally guide Go to specialist, imaging and/or infusion sites.
The failure of aducanumab is the epitome of the medical industry consortium’s decades of presence in Alzheimer’s disease, distorting science and policy, and limiting other promising research and action avenues for brain health and dementia patients. Of care.
The core of this question is that the field has become rigid in an absolutely unscientific way. Amyloid cascade hypothesis——That is, it is believed that amyloid is toxic and triggers a process that destroys cell function. Although the causal role of the protein is unclear, it has disproportionately used federal, foundation and pharmaceutical/venture capital funds for amyloid research.Indeed, until 40% are in their 70s There is amyloid deposits, but the cognition is normal. Amyloid deposits are not causal in themselves, but part of the brain injury response, which is still a possibility.
In addition, although the label of “Alzheimer’s disease” is single, it is increasingly understood as heterogeneous The syndrome involves not only the hallmark amyloid plaques and tau tangles, but also other features such as Vascular changesIn fact, most clinical “Alzheimer’s disease” cases are actually observed Mixed dementiaIt may not be surprising that “attacking” one aspect of the syndrome (amyloid) did not “cure” Alzheimer’s disease.However, it Yes Surprisingly, the field cannot modify or abandon the amyloid hypothesis based on evidence to the contrary. This is the stupid effect of the medical-industrial complex, which combines incentives with fame and fortune based on the pursuit of single-mechanism drugs rather than the clear review required by scientific methods.
Composed in this narrow way, the gatekeeper of the agenda of the control field-what Some Known as the “Alzheimer’s Cabal”-exerted strong downward pressure to support the amyloid hypothesis. Journals, conferences, and professional associations promote and reward research that supports traditionally recognized premises. Build a career and obtain consulting opportunities by accumulating publications and funds based on recognized wisdom. At the same time, those who challenge the dominant agenda are marginalized, and money is drained from other plausible theories of causality.arrive question Is it reasonable to expect biotechnology to cure diseases as complex and closely related to age as Alzheimer’s?
The reductionist, industry-driven approach has also narrowed the imagination about how to adapt to the challenges we face in an aging society.As we write in the upcoming book American dementia (Johns Hopkins University Press, 2021). One of the most striking recent findings is that the incidence of dementia has been increasing decline exist America, Canada, this U.K, France, Sweden with Dutch In the past ten years.
This trend has little to do with biotechnology, but has a lot to do with public policy in the mid-20th century, which has increased the total number of years Provide education for those who are now at retirement age (through the GI Act and investment in American state universities), expand healthcare and improve the treatment of risk factors that affect the brain (ie, vascular disease, high cholesterol), a significantly successful smoking cessation program, And deleaded gasoline.Combined, most experts believe that these national actions in the service of public health—including Lancet Dementia Prevention Committee——Enhanced the cognitive reserve of today’s elderly.
An area not occupied by industry may ask whether the 21st-century government is capable of facilitating such demographic actions, focusing on improving the larger institutions, structures, and social processes that benefit brain health.It can be said that realizing universal healthcare and higher education and solving the country’s aging water pipe infrastructure (which has produced modern Leadership crisis) Is expected to make similar contributions to brain health within a few decades. Providing long-term care insurance will also provide material protection for the elderly currently living in an unstable environment. In this case, the US government will not pay for care through Medicaid until they have basically spent all their assets.
In addition, we have observed the profound influence of art in the dementia care environment during our seven years of work. music, dance, storytelling, Expressive artwork, gardening, Intergenerational activities, Pet therapy As well as other creative, relationship-oriented methods that use typical elements of our humans to improve the quality of life of the elderly and their caregivers more than current drugs (including aducanumab). These “social drugs” are worth our investment, even if they are not commodities that will ultimately generate income for industry.
In the end, aducanumab reflects the forces that led the field of Alzheimer’s disease astray in the 21st century. When the industry promotes research incentives, when a hypothesis becomes “too big to fail”, we will waste scarce resources, waste precious time, and fail to properly adapt to one of the main challenges of our time.
This is an opinion and analysis article; opinions expressed Author or author Not necessarily those Scientific american.