DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Small-Molecule Efflux Inhibitor for Enhanced Treatment of Amyotrophic Lateral Sclerosis

Principal Investigator: BUNT, ANTONIUS M
Institution Receiving Award: IZUMI BIOSCIENCES INC.
Program: ALSRP
Proposal Number: AL150121
Award Number: W81XWH-16-1-0072
Funding Mechanism: Therapeutic Development Award
Partnering Awards:
Award Amount: $1,450,000.00


PUBLIC ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal neurodegenerative disease where patients experience a transient benefit from the only approved drug, riluzole, due to activation of two pumps in the diseased nervous tissues that remove drugs and cause multidrug resistance. In ALS mice, subcutaneous elacridar enhanced riluzole activity and prolonged survival.

Izumi Biosciences is developing oral IZ10023 for testing in patients. The project objectives are: (1) Test various dose combinations of IZ10023 with riluzole in mice and rats to inform dosing in ALS patients. (2) Identify Food and Drug Administration-mandated safety studies. (3) Manufacture current Good Manufacturing Practice drug supplies.

In subsequent patient studies, we seek to confirm that blocking ALS-induced activation of two pumps will enhance riluzole safety and efficacy. Pump blockade by IZ10023 may facilitate future drug combinations to further improve the outcomes of ALS and possibly Alzheimer patients.