Clinical trials of new drugs for Alzheimer disease

Abstract

Alzheimer disease (AD) accounts for 60-70% of dementia cases. Given the seriousness of the disease and continual increase in patient numbers, developing effective therapies to treat AD has become urgent. Presently, the drugs available for AD treatment, including cholinesterase inhibitors and an antagonist of the N-methyl-D-aspartate receptor, can only inhibit dementia symptoms for a limited period of time but cannot stop or reverse disease progression. On the basis of the amyloid hypothesis, many global drug companies have conducted many clinical trials on amyloid clearing therapy but without success. Thus, the amyloid hypothesis may not be completely feasible. The number of anti-amyloid trials decreased in 2019, which might be a turning point. An in-depth and comprehensive understanding of the contribution of amyloid beta and other factors of AD is crucial for developing novel pharmacotherapies. In ongoing clinical trials, researchers have developed and are testing several possible interventions aimed at various targets, including anti-amyloid and anti-tau interventions, neurotransmitter modification, anti-neuroinflammation and neuroprotection interventions, and cognitive enhancement, and interventions to relieve behavioral psychological symptoms. In this article, we present the current state of clinical trials for AD at clinicaltrials.gov. We reviewed the underlying mechanisms of these trials, tried to understand the reason why prior clinical trials failed, and analyzed the future trend of AD clinical trials.

Therapeutic Effects of Human Amniotic Epithelial Stem Cells in a Transgenic Mouse Model of Alzheimer’s Disease

“…Alzheimer's disease (AD), a progressive neurodegenerative disorder, is characterized by memory loss and cognitive decline sufficient to interfere with daily life. The major pathological hallmarks of AD are senile plaques consisting of amyloid fibrils and neurofibrillary tangles made of hyperphosphorylated tau protein [1]. AD is the most common cause of dementia among older adults.…”

Sex-Specific Cross Tissue Meta-Analysis Identifies Immune Dysregulation in Women with Alzheimer’s Disease

“…Sex also interacts with apoE isoform status, where females with the apoE4 isoform are at increased risk compared to males 27-29 . Despite the clear therapeutic potential to better understanding these pathophysiological patterns, there is still little understanding of the mechanisms underlying sexspecific differences in AD.With the rising prevalence of AD, it is critical to facilitate the development of robust means to detect AD early and discover therapeutic interventions [30][31][32][33] . Technological innovations and the increasing availability of large transcriptomic datasets present worthwhile avenues to study and characterize the molecular underpinnings of AD stratified by sex.…”

“…With the rising prevalence of AD, it is critical to facilitate the development of robust means to detect AD early and discover therapeutic interventions [30][31][32][33] . Technological innovations and the increasing availability of large transcriptomic datasets present worthwhile avenues to study and characterize the molecular underpinnings of AD stratified by sex.…”

Broad kinase inhibition mitigates early neuronal dysfunction and cognitive deficits in tauopathy

“…No cure for tauopathies exists, and current treatment strategies are palliative (1,2). Several clinical trials have targeted toxic tau species through immunotherapies or by inhibiting tau post-translational modifications and fibrillization with mixed results (1)(2)(3)(4). However, the disease etiology of tauopathies, AD in particular, are almost certainly multifactorial.…”