Combination Therapy of Anti-Tau and Anti-Amyloid Drugs for Disease Modification in Early-Stage Alzheimer’s Disease: Socio-Economic Considerations Modeled on Treatments for Tuberculosis, Hiv/Aids and Breast Cancer

Abstract

Current drugs for treatment of mild to severe dementia of the Alzheimer’s type include cholinesterase inhibitors and the NMDA non-competitive receptor antagonist memantine. There is controversy as to the additive benefit of these symptomatic drugs, and their effects are clinically modest. Patients with Alzheimer’s disease (AD) are known to have characteristic pathology, including senile plaques with amyloid beta-protein aggregates and neurofibrillary tangles with assembled tau proteins, which start in the hippocampus and spread to neighboring areas. Amyloid and tau modifying drugs are under clinical testing. Based on this pathophysiology, it is crucial to investigate whether anti-amyloid and anti-tau combined therapy would show efficacy in early stage of AD, beyond what could be achieved with anti-amyloid or anti-tau monotherapy. It is equally important to consider the socio-economic implications of such a combination therapy, if effective. We hypothesize that the high costs of combination therapy for early-stage AD patients will require societal and public health initiatives to ensure universal access to AD treatment. In order to better predict these socio-economic implications, we summarize the management of other combination therapies used for tuberculosis, HIV/AIDS, and breast cancer, based on a database search of PubMed and other relevant sources. We put forward a framework for testing a potential anti-amyloid and anti-tau disease modifying combination therapy for early-stage AD patients and present an analysis of the socio-economic implications of such a combination therapy.

Recent updates in the development of small molecules as potential clinical candidates for Alzheimer's disease: A review

“…The simultaneous application of a palliative agent like cholinesterase inhibitors, an antioxidant and an anti‐inflammatory agent might be one such strategy. Use of combination therapies in other diseases, like human immunodeficiency virus‐1 and cancer, have been successful and thus may provide more effective results than targeting single mechanism at a time (Tomaszewski et al, 2016). The combination therapy is of great flexibility and significance (Figure 3) as it can target more than two targets (such as tau‐ and amyloid‐targeting therapies) or a single target in two different ways (such as two amyloid‐targeting therapies) or it may be used for more than one delivery method (such as intravenous and oral).…”

The Time for Combination Therapy Research in Alzheimer’s Disease is Now1

“…It is only practical to expand our portfolio of combination trials, now, testing multiple pathological targets simultaneously. Similar research modalities have been successfully deployed in other multifactorial diseases such as HIV, diabetes, tuberculosis, and various oncological conditions [1]. Combination therapy may trigger a synergistic effect.…”