Addressing Alzheimer's disease pathology through combinatorial therapeutic interventions

Abstract

In recent years, neurodegenerative diseases have become a greater focus area of research due to their significant prevalence and complex pathophysiology. The neurodegenerative disease known as Alzheimer's Disease (AD) is characterized by its variable and progressive symptom expression, which may include memory loss, reduced cognitive function, abnormal behavior, and eventually neuronal cell death. The mechanisms underlying the expression of this disease are continuously being researched, and notable processes that have been implicated in both AD origination and progression include plaque accumulation and neuroinflammation. As a result, a multitude of therapeutic, disease-intervening drugs have been developed to address the different underlying causes of AD. Given the complex pathology of AD and the increasing number of developing therapeutics, combination therapy has become increasingly relevant in neurodegenerative disease research. In this thesis, I examine two neurodegenerative disease treatments with phase III trial data; an anti-amyloid-beta antibody called Lecanemab, and an anti-inflammatory tyrosine kinase inhibitor called Masitinib. I attempt to predict potential outcomes of drug mechanism interaction, as well as overall drug complementarity between these drugs. Furthermore, I outline a theoretical, alternating combinatorial approach for treatment using these drugs–including dosages and dosage periods for each drug. The conclusions drawn from this analysis identify potential synergistic effects between the two drugs, which may increase observable benefits in AD patients greatly, as well as potential areas of concern for antagonism. Additionally, I highlight the need for additional in vivo or clinical research into combination therapy, both for these drugs and also for the field as a whole within the context of neurodegenerative disease.