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Nanomedicine study with rabbits hints at possible breakthrough for cerebral palsy: US researchers

Friday, April 20, 2012
By Kerry Sheridan, AFP


WASHINGTON--A new treatment helped rabbits born with cerebral palsy regain near-normal mobility, offering hope of a potential breakthrough in treating humans with the incurable disorder, researchers said Wednesday.

The method, part of the growing field of nanomedicine, worked by delivering an anti-inflammatory drug directly into the damaged parts of the brain via tiny tree-like molecules known as dendrimers.

Baby rabbits treated within six hours of birth showed “dramatic improvement in motor function” by the fifth day of life, said lead author Sujatha Kannan of the National Institute of Child Health and Human Development Perinatology Research Branch.

The study appears in the journal Science Translational Medicine.

Rabbits who were born immobile due to cerebral palsy were moving around at “almost ... normal healthy levels by day five,” said an accompanying article in the same journal by Chicago pediatrician Sidhartha Tan.

The drug was one that is commonly used to treat people who overdose on acetaminophen, known as N-acetyl-L-cystine or NAC, and was given at a 10 times smaller amount.

However, it was successful because the nanodelivery method allowed it to cross the blood-brain barrier and swiftly shut down inflammation in the brain.

Kannan said her team used rabbits because, like humans, their brains develop some before birth and some after birth, whereas most other animals are born with their motor abilities already formed.

“An advantage of that is we can test therapies and look at the improvement in motor function using this kind of animal model,” she said.

While experts say it may be many years before it will be known if this approach can be used in human babies, the research shows an important proof of concept that some type of early intervention can reverse brain damage.

“The importance of this work is that it indicates that there is a window in time, immediately after birth, when neuroinflammation can be identified and when treatment with a nanodevice can reverse the features of cerebral palsy,” said co-author Roberto Romero, an obstetrician at the National Institute of Child Health and Human Development.

Cerebral palsy affects about 750,000 children and adults in the United States, and its prevalence rate is about 3.3 per 1,000 births, according to Romero.

The disorder can cause severe difficulties controlling muscles, and inability to walk, move or swallow. Some patients may also suffer cognitive delays and developmental abnormalities.

Cerebral palsy can be caused by infections in the mother during pregnancy, head injury, or birth complications. The condition is often linked to premature birth, a phenomenon that is on the rise.

Often, cerebral palsy is not diagnosed until age 2.

“By the time we make the diagnosis there is very little we can do,” said Romero, describing cerebral palsy as “a lifelong condition with no cure.”

Next, the team hopes to study whether the gains in mobility seen in the rabbits will last into adulthood. Further study must also be done to determine what may be a safe dose for infants suspected of having cerebral palsy.

Kannan said the treatment appeared to help improve the white matter in the rabbits' brain, where the centers of motion are located, and also gray matter where intelligence lies, though this was harder to measure in the rabbits.

This particular study focused on cerebral palsy that was caused by inflammation and infection. The pregnant rabbits were exposed to bacterial endotoxins which caused their offspring to develop a cerebral-palsy like condition at birth.

It remains unknown whether the treatment could help older children or adults with cerebral palsy, but more research could shed light on those groups, too, said Kannan.

For now, the earlier the treatment is given, “the better we expect the response would be,” she said.

Tan, who was not involved in the research, said the study offers hope that nanomedicine may open doors to treating a host of incurable disorders, including cerebral palsy.

“A lot remains unknown about the developing brain,” wrote Tan.

“The use of nanomaterials in perinatal brain injury opens up new vistas in the realm of diagnostics, imaging and drug delivery for newborn babies.”

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