Given the rapidly ageing demographic profiles in most areas of the world, new therapeutic interventions for AD are urgently needed that can slow or perhaps even prevent disease progression; ideally these treatments would restore normal brain function

Given the rapidly ageing demographic profiles in most areas of the world, new therapeutic interventions for AD are urgently needed that can slow or perhaps even prevent disease progression; ideally these treatments would restore normal brain function. In recent years, a number of drug candidates targeting amyloid- (A) peptide have advanced into randomized controlled clinical trials. reproducible delivery of a known amount of therapeutic antibodies to the patient and rapid clearance of those antibodies if side effects develop. A disadvantage is the requirement for repeated infusions of antibodies over time. After more than a decade of research, anti-amyloid immunotherapy remains one of the most promising emerging strategies for developing disease-modifying treatments for AD. In this review, we examine the presently ongoing A-directed immunotherapies that have passed clinical development Phase IIa. Keywords:Alzheimer’s disease, amyloid-beta, clinical trials, immunotherapy == Introduction == Current treatment options for Alzheimer’s disease (AD) are limited to medications that reduce dementia symptoms but do not arrest or reverse the underlying neurodegenerative disorder. The available drugs include three acetylcholinesterase inhibitors (donepezil, rivastigmine and galantamine) and one N-methyl-D-aspartate (NMDA) receptor inhibitor (memantine). These two classes of medication target, respectively, cholinergic and glutaminergic neurotransmitter derangements commonly associated with AD. However, neither class of medication is thought to significantly alter the causal pathways in AD or prolong the lives of patients with the disease. Given the rapidly ageing demographic profiles in most areas of the world, new therapeutic interventions for AD are urgently needed that can slow or perhaps even prevent disease progression; ideally these treatments would restore normal brain function. CP-724714 In recent years, a number of drug candidates targeting amyloid- (A) peptide have advanced into randomized controlled clinical trials. These include tarenflurbil (Myriad Genetics, Salt Lake City, UT, USA), semagacestat (Eli Lilly and Organization, Indianapolis, IN, USA), tramiprosate (Neurochem Inc., Laval, Canada), ELND006 and AN1792 (Elan Corporation, Dublin, Ireland) and ponezumab (Pfizer, New York, NY, USA). However, most have failed because of security issues or lack of effectiveness1. Building upon the lessons learned from these failures, additional drug development programmes are being carried out with the aim of getting safer and more effective treatments for AD. Understanding of the pathogenesis of AD offers improved greatly since the early 1990s, providing rise to optimism that better treatments can now become developed. AD is currently perceived as a protein aggregation disorder. The A peptide is definitely central to the pathogenesis2, initiating and CP-724714 traveling a cascade that leads to the dysfunction of neurons and, finally, to dementia. Several mutations in rare familial forms of the disease result in early-onset AD, either by increasing A production or by elevating the A42/40 percentage. Improved A levels accelerate aggregation of the peptide. Recently, a rare polymorphism for the A precursor protein (APP) has been identified that Rabbit polyclonal to ECHDC1 appears to decrease synthesis of A by approximately 40% and reduces the risk of AD3. The production, aggregation and clearance of A are therefore all attractive and feasible focuses on for drug development. Enzymes such as – or -secretase, which regulate the processing of APP and A production, can be inhibited by small molecules. However, it has proven difficult to make -secretase inhibitors that are specific for the prospective substrates and at the same time are nontoxic, and -secretase inhibitors remain early in development46. Furthermore, probably the most common late-onset sporadic form of AD is not clearly associated with A overproduction and may be more closely related to decreased A clearance7. With this context, the value of using secretase CP-724714 inhibitors that lower A production without increasing clearance to treat AD is uncertain. Treatment designed to improve the clearance of A and/or prevent its build up are therefore becoming tested. ==.