A Wayne State University School of Medicine professor has received a $2.9 million award from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health to develop a better understanding of the intersection of two disorders, sepiapterin reductase deficiency and cerebral palsy.

Cerebral palsy is a disabling condition caused by damage to the developing brain typically before birth that affects movement and posture in children. Estimates from the U.S. Centers for Disease Control and Prevention suggest that the lifetime health care cost for one individual with CP is more than $1 million. 

SPR deficiency is a rare neurometabolic genetic disorder characterized by very low levels of certain neurotransmitters meant to transmit impulses from one nerve cell to another. Common symptoms include motor and cognitive disorders.

The five-year award will study changes in pathways of ferroptosis, a form of cell death, and its involvement in deficiency of tetrahydrobiopterin (BH4) caused by a mutation in the SPR gene. BH4 is a naturally occurring chemical substance that helps to enhance the functions of certain enyzmes.

The study will be led by Sidhartha Tan, M.D., professor in the Department of Pediatrics in the School of Medicine at Wayne State.

“The human disease that is targeted is congenital deficiency of sepiapterin reductase (SPR), which results in motor deficits that often mimic CP,” Tan said. “SPR is an enzyme that is involved in the biosynthesis and recycling of BH4. The exciting thing about this project is that for the first time in the field of Developmental Neuroscience, we are going to use transgenic rabbits that involve the insertion of a human gene mutation causing congenital SPR deficiency. This study will aim to understand the early events around critical cell death that cause motor deficits, and ultimately, provide understanding for the development of much-needed therapies for prevention of motor deficits from congenital BH4 deficiency and CP.”

“Collaboration provides researchers the opportunity to learn how complementary disciplines can offer innovative solutions to complex problems,” said Timothy Stemmler, Ph.D., interim vice president for Research at Wayne State University. “This important research study would not be possible without the expertise of Dr. Tan’s collaborative partners, Jie Xu, Ph.D., research associate professor of Internal Medicine from our University Research Corridor partner institution, the University of Michigan, and Jeannette Vasquez Vivar, Ph.D., professor of Biophysics at the Medical College of Wisconsin. Together they will work on developing advances that may lead to new therapies for prevention of these disorders in the future.”

The project number for this National Institute of Neurological Disorders and Stroke of the National Institutes of Health R01 award is NS130258.