Research ArticleCEREBRAL PALSY

Dendrimer-Based Postnatal Therapy for Neuroinflammation and Cerebral Palsy in a Rabbit Model

Science Translational Medicine  18 Apr 2012:
Vol. 4, Issue 130, pp. 130ra46
DOI: 10.1126/scitranslmed.3003162

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One Hop at a Time

Cerebral palsy (CP) is a developmental disorder caused by injury to a baby’s brain while it is still developing, either in the womb or during the early months of life, but is often not diagnosed until children are 2 to 3 years of age. There is no cure for CP, and the best option for affected children is intensive physical therapy to improve motor skills. Now, Kannan et al. have designed a dendrimer-based therapeutic for treating this developmental disorder in baby rabbits (kits), opening the door to new treatment options in humans.

The authors chose to use the rabbit model of CP, which replicates the neuroinflammation seen in human brains as well as the motor deficits in children. To generate this model, Kannan and colleagues injected Escherichia coli toxin into the rabbit mother’s uterus at about 90% term gestation. When the kits were born, they were administered either a saline solution, a free drug known as NAC (N-acetyl-l-cysteine), or a dendrimer-NAC (D-NAC) conjugate. This postnatal “rescue” with D-NAC, given on day 1 of life, allowed CP kits to develop normally, able to walk and hop. The successfully treated kits also had neuron counts and low inflammation similar to healthy control animals. By comparison, NAC alone or saline had no effect. The authors believe that conjugating NAC to the dendrimers promoted greater uptake by activated microglia and astrocytes, with no toxicity to surrounding neurons. Although still in preclinical testing in rabbits, this dendrimer-drug conjugate shows promise for postnatal treatment of babies suspected of having CP.