Guilford Pharmaceuticals Inc. demonstrated proof-of-principle for its stroke program in a Nature Medicine paper showing that mice deficient in an enzyme called poly(ADP-ribose) polymerase (PARP) are resistant to neurotoxicity and have reduced infarct volume after a stroke.

The work was done by scientists at Johns Hopkins University, which has granted GLFD (Baltimore, Md.) exclusive license to the use of PARP inhibitors to prevent neurotoxicity.

The Hopkins researchers showed that PARP activity was required for neurotoxicity induced by the neurotransmitter NMDA or the signaling molecule nitric oxide (NO). Cells from homozygous knockout mice (completely lacking PARP) were completely resistant to such toxicity, and cells from heterozygous mice (with only one copy of PARP instead of two) were 73 percent resistant.

In a mouse model, infarct volume following stroke was reduced by 80 percent in mice lacking PARP (15.4 mm3 versus 69.0 mm3 in normal mice). Heterozygous animals had a 65 percent reduction in infarct volume (30.1 mm3 versus 69.0 mm3).