WSU Researchers Find ‘Window Of Opportunity’ To Prevent Cerebral Palsy

DETROIT Researchers at the Perinatology Research Branch of the National Institutes of Health, housed at the Wayne State University School of Medicine and the Detroit Medical Center, have demonstrated that a nanotechnology-based drug treatment in newborn rabbits with cerebral palsy enabled dramatic improvement of movement disorders, and the inflammatory process of the brain that causes many cases of CP.

The findings strongly suggest that there is an opportunity immediately after birth for drug treatment that could minimize CP.

The study is the first to show that an anti-inflammatory drug delivered with a nanodevice can dramatically improve the symptoms of CP in an animal model.

The report, Dendrimer-Based Postnatal Therapy for Neuroinflammation and Cerebral Palsy in a Rabbit Model, will be released Thursday in the prestigious journal Science Translational Medicine, published by the American Association for the Advancement of Science.

The key finding of this work is that early identification of neuroinflammation allows postnatal treatment, said Roberto Romero, M.D., Chief of the Perinatology Research Branch of the NIH and an author of the study. This suggests that there is a window of opportunity to prevent cerebral palsy, and that the condition may be preventable.

Cerebral palsy is a disorder of the developing brain that affects motor skills and muscle coordination, often not diagnosed until the age of two or three years in children. The United Cerebral Palsy Foundation, a national advocacy and support group, estimates that 764,000 children and adults in the United States have CP. According to the U.S. Centers for Disease Control and Prevention (CDC), 100,000 babies born in the U.S. develop CP annually. A 2009 report by the CDC indicated the prevalence of the condition at 3.3 per 1,000 births. Worldwide, the CDC estimates the prevalence of CP births to range from 1.5 to 4 for every 1,000 births.

Risk factors for the condition include low birth weight and premature birth. Children born before the 32nd week of pregnancy are at high risk for developing CP. Intrauterine infection and/or inflammation is a major risk factor for CP.

Microglia immune cells in the brain play an important role in remodeling and growth during fetal and postnatal periods. Activation of these cells can cause an exaggerated inflammatory response, leading to brain injury and CP. Treatment is problematic because inflammation and the resulting injury can be spread throughout the brains white matter. Transporting drugs across the blood-brain barrier also represents a challenge.

The PRBteam hypothesized that it was possible to deliver a drug using a tiny device (or nanodevice) that would cross the blood-brain barrier and target the activated cells in the brain involved in neuroinflammation (microglia and astrocytes).

The researchers used a rabbit model of congenital CP because it replicates the type of neuroinflammation found in human brains and the resulting motor deficits observed in children with CP. The method consisted of exposing fetal rabbits to endotoxin (a component of bacteria). Endotoxin induced inflammation of the fetal brain but did not induce the onset of labor. When the rabbits were born, they had great difficulties walking or hopping. The experiment consisted of treating affected rabbits intravenously with either a saline solution, a drug known as NAC (N-acetyl-L-cysteine) or a dendrmer coupled with NAC, also known as a D-NAC conjugate. Rabbits with CP treated with D-NAC on the first day of life showed a dramatic improvement and, within five days, were able to walk and hop, which those without treatment were not able to do. Rabbits treated with the NAC conjugate also showed a higher neuron count and lower evidence of inflammation compared to untreated animals.

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WSU Researchers Find ‘Window Of Opportunity’ To Prevent Cerebral Palsy