Disease-modifying treatments for Alzheimer’s disease

Abstract

The first drugs developed for Alzheimer's disease (AD), acetylcholinesterase inhibitors (AChEI), increase acetylcholine levels, previously demonstrated to be reduced in AD. To date, four AChEI are approved for the treatment of mild-to-moderate AD. A further therapeutic option available for moderate-to-severe AD is memantine. These treatments are symptomatic, whereas drugs under development are intended to modify the pathological steps leading to AD, thus acting on the evolution of the disease. For this reason they are have been termed 'disease-modifying' drugs. To block the progression of the disease they have to interfere with the pathogenic steps responsible for the clinical symptoms, including the deposition of extracellular amyloid beta (Ab) plaques and of intracellular neurofibrillary tangles, inflammation, oxidative damage, iron deregulation and cholesterol metabolism. In this review, new perspectives will be discussed. In particular, several approaches will be described, including interference with Ab deposition by anti-Ab aggregation agents, vaccination, g-secretase inhibitors or selective Ab-lowering agents; interference with tau deposition by methylthioninium chloride; and reduction of inflammation and oxidative damage.

Cl-NQTrp Alleviates Tauopathy Symptoms in a Model Organism through the Inhibition of Tau Aggregation-Engendered Toxicity

“…Current approved drugs ameliorate symptoms but do not have profound disease-modifying effects [27,28,29]. Thus, there is great medical need for the development of novel therapeutic strategies that would target the pathogenic mechanisms underlying AD.…”

“…Current treatments of AD target disease symptoms, trying to counterbalance the neurotransmitter disturbance using cholinesterase inhibitors and NMDA (N-methyl- D -aspartate) antagonists, and the clinical outcomes to date are modest at best [27,28,29]. Thus, there is grave need for the development of novel therapeutic strategies that would target the underlying pathogenic AD mechanisms.…”

Chemical and Physical Approaches for the Treatment of Alzheimer's Disease

“…It is believed that the benefits of the usage of AChEIs outweigh their risks and costs. AChEIs now are considered as primary therapy for the patients with mild to moderate AD [12].…”

“…As a vital step of AD pathogenesis, Aβ production is a potentially crucial target for disease-modifying therapeutic methods which attempt to restrain the disease at early stages [12,19].…”

Management of Alzheimers Disease: Role of Existing Therapies, Traditional Medicines and New Treatment Targets

“…Recent research is directed to identify and formulate the drugs that will modify the pathological steps, which include deposition of AP, neurofibrillary tangles, oxidative damage, inflammation, iron deregulation and cholesterol metabolism [69,70] . The most studied drug in this regard is the antiamyloid aggregation agent, tramiprosate (homotaurine), a glycosaminoglycan (GAG) mimetic, which is derived from marine red algae.…”