Prior Funding

This proposal addresses an unmet medical need: the study of pathogenesis and
treatment of periventricular leukomalacia (PVL). PVL is the predominant form of
brain injury in premature infants and the most common cause of cerebral palsy.
PVL affects up to 50% of the 60,000 premature infants born in the U.S. every
year. Currently no therapy is available for this serious human disorder in part
because the pathogenesis is not well understood, and this area of research is
underfunded. PVL is characterized by selective cerebral white matter damage.
The biology of cerebral white matter response in brain injury is poorly
understood and woefully understudied. We propose to study the signaling
mechanisms of this injury using experimental models of PVL in mice that we
have developed. Based on our preliminary studies, we will specifically focus on
nuclear PARP-1 and mitochondrial AIF, using both genetic deletion and
pharmacological inhibition. This research will likely provide new insights into the
pathogenesis of PVL, for which no therapy currently exists. We are determined
to establish a vigorous and innovative research program in this previously
neglected area of medical research. We believe that this specific research
theme focusing on investigating unique mechanisms of cerebral white matter
injury underlying PVL is highly relevant to the central missions of the Feldstein
Medical Foundation.