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Technical report
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# Aducanumab as a Novel Treatment for Alzheimer’s Disease: A Decade of Hope, Controversies, and the Future

### Abstract

Alzheimer’s disease (AD) is the most common type of dementia and is among the leading cause of death in the United States. Its worldwide prevalence is around 50 million and is projected to double by 2050. Deposition of beta-amyloid (also known as amyloid-beta) peptides (beta 40 and 42) in the brain continues to be the most widely accepted disease mechanism. Until recently, only two Food and Drug Administration (FDA)-approved groups of medications, namely, cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists, were available for symptomatic treatment with limited efficacy. Disease-modifying therapeutics, keenly desired by clinicians and patients alike, have long been elusive until recently. The FDA’s Accelerated Approval Program for the approval of a new agent, aducanumab, is being considered a step in this direction by some, but not without controversy. Aducanumab, marketed as Aduhelm by Biogen, has been shown to lower beta-amyloid plaques in the brain. Biogen believes this will lead to improvement in cognition and functioning in patients with AD. However, within a month of this approval, the FDA has called for investigations into interactions between representatives of Biogen and the FDA preceding the approval of Aduhelm. This report provides an overview of the controversy surrounding the FDA’s Accelerated Approval Program as it pertains to the approval of Aduhelm, and the potential impact of these issues on researchers, clinicians, patients, and families in the ongoing battle against this devastating, debilitating, and ultimately fatal illness.

### Introduction

Alzheimer’s disease (AD) is the most common (60-80%) subtype of dementia and the sixth leading cause of death in the United States [1,2]. Its overall worldwide prevalence is close to 50 million and is projected to more than double by 2050. The deaths due to AD increased by 89% from 2000 to 2014 in the United States, and the overall economic burden exceeds 500 billion dollars. Although its etiology is multifactorial, deposition of beta-amyloid peptides (beta 40 and 42) remains the most widely accepted mechanism. Until recently, only two Food and Drug Administration (FDA)-approved classes of medications, namely, cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists, were available for symptomatic treatment with limited efficacy. After a decade of extensive research, the unique disease-modifying therapeutics (DMT) have been a hope for many clinicians, patients, and families to have the desired efficacy and outcomes concerning this debilitating progressive disease.

### Conclusions

While aducanumab (Aduhelm) offers some degree of hope to many in the fight against AD, the controversy surrounding its approval has left many others in doubt as to the veracity of the FDA’s Accelerated Approval Program. Add to this, its prohibitive cost, one cannot help but perceive the immediate future, at least, as remaining bleak despite the presence of a new and potentially promising molecule in the battle against AD. Although questions remain unanswered at this juncture, the authors express cautious optimism that there is indeed reason to be hopeful. It is our hope that this new molecule will pave the way for further research into DMT, just as tacrine did for cholinesterase inhibitors.

### References

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### Author Information

###### Ethics Statement and Conflict of Interest Disclosures

Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Technical report
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