Inhibiting drug efflux transporters improves efficacy of ALS therapeutics
Abstract
Research identified promising therapeutics in cell models of Amyotrophic Lateral Sclerosis (ALS), but there is limited progress translating effective treatments to animal models and patients, and ALS remains a disease with no effective treatment. One explanation stems from an acquired pharmacoresistance driven by the drug efflux transporters P‐glycoprotein (P‐gp) and breast cancer‐resistant protein (BCRP), which we have shown are selectively upregulated at the blood‐brain and spinal cord barrier (BBB/BSCB) in ALS mice and patients. Pharmacoresistance is well appreciated in other brain diseases, but overlooked in ALS despite many failures in clinical trials.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 21, 2014
- Source ID
- 10.1002/acn3.141
Entities
People
- Angelo C. Lepore
- Davide Trotti
- Dena Jacob
- Ke Li
- Michael R. Jablonski
- Ni J. Meng
- Piera Pasinelli
- Shashirekha S. Markandaiah
- Victoria Gennaro
Organizations
- Missile Defense Agency
- National Institutes of Health
- Thomas Jefferson University
- United States Department of Defense