alexa Novel Treatment Strategies for Neurological and Neurodegenerative Diseases

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Novel Treatment Strategies for Neurological and Neurodegenerative Diseases

Neurological and neurodegenerative diseases are a major burden not only to those individuals affected but also to families, caregivers and society as a whole. With life expectancy on the rise, we are facing new challenges of higher lifetime prevalence rates of neurodegenerative disorders and the associated increases in health care costs. In recent years, preclinical and basic science efforts have resulted in significant advances in developing and testing novel preclinical models and assessing potential therapeutic agents.


Many of these attempts have focused on neuroprotective strategies. The concept of neuroprotection is based on the assumption that neurodegenerative processes associated with disease and/or aging can be slowed, halted, or even reversed by therapeutic intervention. Common targets for neuroprotection include increased levels in oxidative stress, mitochondrial dysfunction, excitotoxicity, inflammatory processes, and protein aggregation. Unfortunately however, most clinical trials on neuroprotection have failed despite promising preclinical data. One exception is the drug Memantine, FDA-approved as a cognitive enhancer in moderate to severe Alzheimer’s disease.


Does this mean that pursuing drug discovery targeted at neuroprotection for neurodegenerative and neurological disorders is a futile undertaking? Certainly not! Rather, several critical issues have to be considered to increase the chances of a successful translation of preclinical insights to meaningful clinical trials. These include the inherent limitations of in vitro studies, the suitability of preclinical animal models to mirror the various pathologies underlying human neurodegenerative diseases, and the lack of drug-likeness of most lead compounds. Furthermore, PD/PK studies are often ignored during early stages of drug discovery, although they may predict future challenges in the drug development pipeline.


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