Science News

Steps to treating cerebral palsy

Mon, 23rd Apr 2012

Louise Anthony

Drugs delivered directly to the brain by nanoparticles can reverse the symptoms of cerebral palsy in animals.

DendrimerOne in five hundred children is affected by cerebral palsy, which causes difficulties with co-ordination and movement, known as motor impairment.  The disease is thought to be the consequence of inflammation in the brain after birth, and researchers at Wayne State University and the National Institute of Child Health and Human Development have developed a nanoparticle drug-delivery system known as a “dendrimer” which can directly target cells known as microglia that are responsible for this inflammation.

By chemically attaching an anti-inflammatory drug called N-acetyl-L-cysteine (NAC) to the nanoparticles, it is delivered directly to the affected parts of the brain - making it effective at a tenth of the dose.  

Newborn rabbits with cerebral palsy, induced by injecting a toxin before birth, were given a single injection of the NAC-nanoparticle compound into the bloodstream at birth - and four days later, they showed dramatic improvements in their co-ordination and muscle tone, two of the problems people with severe cerebral palsy often have.  In fact, the rabbits were moving almost as well as their healthy control counterparts at day five.

Compared with untreated animals, the rabbits given the new compound had more brain cells (neurons) at five days old– almost as many as in normal rabbits.  They also had more myelin, the structure which wraps around neurons like insulation, helping them to convey messages efficiently. 

“This shows that targeted shutting-down of ongoing neuroinflammation can have a very significant impact in cerebral palsy,” says Dr. Rangaramanujam Kannan, one of the study authors.  “We were able to reverse the motor impairment, which was not thought to be possible.”  In essence, their work strongly implies that at least some of the damage responsible for cerebral palsy happens after birth.

The nanoparticles have not yet been approved for use in humans, and more work is needed before potential clinical trials - the rabbits were only followed up to the fifth day after birth, so the long-term benefits are unknown, and side-effects could develop.  But Dr. Kannan says that experiments are ongoing “to see whether this improvement can be sustained until adulthood.”

Despite the potential benefits of the new treatment, spotting those infants that may benefit from this therapy at or close to birth remains a challenge, because most children are not formally diagnosed with cerebral palsy until they are two years old, well outside the time frame explored by the present intervention.  It is also not known how long the inflammation lasts, so there may still be ongoing inflammation at two years old, but, as Dr. Kannan says, “the earlier we treat it, the better we would expect the outcome to be.”


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