Disease-modifying therapy for Alzheimer's disease: Challenges and hopes

Despite enormous efforts to develop disease-modifying drugs for Alzheimer's disease (AD), effective therapies have yet to be found. We have endured failure for a number of reasons, such as low specificity in drug candidates, inaccurate diagnosis and incorrect timing in the intervention. To help overcome these problems, modern research findings have been incorporated into new criteria and guidelines for the clinical diagnosis of AD. In addition, attempts to intervene during the earliest stages of the disease are planned, as this is probably when AD is most receptive to disease-modifying therapies. We discuss these issues and provide perspective into the future of drug development.

Disease-modifying therapy for Alzheimer's disease: Challenges and hopes

Despite enormous efforts to develop disease-modifying drugs for Alzheimer's disease (AD), effective therapies have yet to be found. We have endured failure for a number of reasons, such as low specificity in drug candidates, inaccurate diagnosis and incorrect timing in the intervention. To help overcome these problems, modern research findings have been incorporated into new criteria and guidelines for the clinical diagnosis of AD. In addition, attempts to intervene during the earliest stages of the disease are planned, as this is probably when AD is most receptive to disease-modifying therapies. We discuss these issues and provide perspective into the future of drug development.

Current status of vaccination therapies in Alzheimer's disease

Alzheimer's disease (AD) is a major health and societal problem and is the predominant cause of dementia. Age is the major risk factor for AD, and with the predicted demographic change to an increasingly elderly population, the prevalence of the disease will reach a staggering 100 million by 2050. Acetylcholinesterase inhibitors such as donepezil, rivastigmine and galantamine offer a modest symptomatic relief for a short period of time in mild-to-moderate AD, and memantine, a low-affinity N-methyl d-aspartate receptor antagonist, is licensed for use in moderate-to-severe AD. However, none of the current therapies is able to alter the course of the disease.

Immunotherapy for Alzheimer's Disease: Rational Basis in Ongoing Clinical Trials

Amyloid-β (Aβ) immunotherapy has recently begun to gain considerable attention as a potentially promising therapeutic approach to reducing the levels of Aβ in the Central Nervous System (CNS) of patients with Alzheimer's Disease (AD). Despite extensive preclinical evidence showing that immunization with Aβ(1-42) peptide can prevent or reverse the development of the neuropathological hallmarks of AD, in 2002, the clinical trial of AN-1792, the first trial involving an AD vaccine, was discontinued at Phase II when a subset of patients immunized with Aβ(1-42) developed meningoencephalitis, thereby making it necessary to take a more refined and strategic approach towards developing novel Aβ immunotherapy strategies by first constructing a safe and effective vaccine.

The Solanezumab Benefit: small but probably real

Prospects for Alzheimer’s immunotherapy appear to have brightened. At the 137th annual meeting of the American Neurological Association in Boston, Massachusetts, researchers presented analyses from Phase 3 trials for two therapeutic antibodies, solanezumab and bapineuzumab. Most of the new data were on solanezumab, Eli Lilly and Company’s humanized monoclonal antibody against the mid-region of monomeric Aβ, and they appeared to deliver the long-awaited signal the amyloid field needed to restore its confidence after a string of clinical setbacks.