Nanomaterials Offer Hope for Cerebral Palsy

Nature | Health

Rabbits with brain injuries hop again after treatment--synthetic molecules affixed with an anti-inflammatory drug--crosses the blood brain barrier

April 18, 2012

By Amy Maxmen of Nature magazine

By tacking drugs onto molecules targeting rogue brain cells, researchers have alleviated symptoms in newborn rabbits that are similar to those of cerebral palsy in children. Cerebral palsy refers to a group of incurable disorders characterized by impairments in movement, posture and sensory abilities.

In general, medicines tend to act broadly rather than influence certain sets of cells in the brain. "You don't expect molecules to enter the brain, and if they do, you don't expect them to target specific cells, and immediately act therapeutically -- but all of this happened," says study co-author Rangaramanujam Kannan, a chemical engineer at the Johns Hopkins University School of Medicine in Baltimore, Maryland. The paper is published today in Science Translational Medicine.

According the US Centers for Disease Control and Prevention, approximately 1 in 303 children have cerebral palsy by age 8, which usually results from neurological damage in the womb, caused by, for example, a kink in the umbilical cord that briefly dimishes the foetus' oxygen, or maternal infection. Such injuries lead to the activation of immune cells in the brain called microglia and astrocytes, which cause further inflammation and exacerbate the damage.

Calming the cells is difficult, because anti-inflammatory drugs don't easily cross the blood-brain barrier. And those that do tend to diffuse nonspecifically.

"What's amazing here is that the authors target the drug directly to the microglia," says Mike Johnston, a paediatric neurologist at the Kennedy Krieger Institute in Baltimore.

The team affixed an anti-inflammatory drug, N-acetyl-L-cysteine (NAC), to synthetic, snowflake-shaped molecules called dendrimers, and injected the conjugates into the bloodstream of newborn rabbits with experimentally injured brains. The dendrimers transported the drug across the blood-brain barrier and released it directly into the activated microglia and astrocytes, halting further inflammation and improving motor function. Control rabbits given NAC alone lost additional brain cells and stumbled in their hops.

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Nanomaterials Offer Hope for Cerebral Palsy