Blood-Brain Barrier Driven Pharmacoresistance in Amyotrophic Lateral Sclerosis and Challenges for Effective Drug Therapies.
Publication/Presentation Date
11-1-2017
Abstract
The blood-brain barrier (BBB) is essential for proper neuronal function, homeostasis, and protection of the central nervous system (CNS) microenvironment from blood-borne pathogens and neurotoxins. The BBB is also an impediment for CNS penetration of drugs. In some neurologic conditions, such as epilepsy and brain tumors, overexpression of P-glycoprotein, an efflux transporter whose physiological function is to expel catabolites and xenobiotics from the CNS into the blood stream, has been reported. Recent studies reported that overexpression of P-glycoprotein and increase in its activity at the BBB drives a progressive resistance to CNS penetration and persistence of riluzole, the only drug approved thus far for treatment of amyotrophic lateral sclerosis (ALS), rapidly progressive and mostly fatal neurologic disease. This review will discuss the impact of transporter-mediated pharmacoresistance for ALS drug therapy and the potential therapeutic strategies to improve the outcome of ALS clinical trials and efficacy of current and future drug treatments.
Volume
19
Issue
6
First Page
1600
Last Page
1614
ISSN
1550-7416
Published In/Presented At
Mohamed, L. A., Markandaiah, S., Bonanno, S., Pasinelli, P., & Trotti, D. (2017). Blood-Brain Barrier Driven Pharmacoresistance in Amyotrophic Lateral Sclerosis and Challenges for Effective Drug Therapies. The AAPS journal, 19(6), 1600–1614. https://doi.org/10.1208/s12248-017-0120-6
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
28779378
Department(s)
Administration and Leadership
Document Type
Article