By Medical Discovery News

Aug. 25, 2012

A child’s symptoms can start with a weak or shrill cry, which seems normal enough. But then other problems appear, such as not being able to swallow or suck properly and having an overly floppy or stiff body. These are early signs of a group of disorders called Cerebral Palsy (CP), which is the No. 1 cause of motor disability in American children and affects over 11,000 new kids every year.

Doctors treat the lifelong symptoms with physical therapy and drugs, but are unable to reverse the brain damage, which happens in the womb for most CP children. Now a study using a nanoparticle has successfully repaired damaged brains in rabbits with CP. A research team engineered a particle small enough to deliver anti-inflammatory drugs to overactive neurons in the brain that are killing healthy cells.

Children with CP have varying types of brain damage due to genetic mutations, maternal infections that affect fetal brain development, lack of oxygen to the fetus or baby, or traumatic brain injury. In many of these cases, two types of immune cells in the brain become activated: microglia and astrocytes. They protect the brain during infection and inflammation, but damage the brain when they go into overdrive, destroying healthy cells.

Controlling neuronal inflammation presents a challenge because most medications can’t get past the blood-brain barrier. R. Kannan led a group from Johns Hopkins University and Wayne State University that found a solution using a nanoparticle called a dendrimer, which is 2,000 times smaller than a red blood cell. Kannan’s team affixed a powerful antioxidant with anti-inflammatory properties onto the snowflake-shaped particle. When intravenously injected into newborn rabbits with an induced form of CP, the drug-laced dendrimers made their way to the brain and were immediately swallowed by the overactive immune cells.

Within five days of treatment, the rabbits showed significant improvement, exhibiting motor skills similar to healthy rabbits. By comparison, rabbits treated with just the antioxidant, unattached to a dendrimer, showed minimal improvement even though they were given 10 times the amount.

An autopsy revealed the brains of rabbits treated with dendrimers had less scarring, less brain cell death, and reduced inflammation. They also had better preservation of myelin, a protective cover around nerves, which is normally stripped by CP and other neurological diseases. This suggests the new treatment has the potential to reverse the disease.

Before human trials can begin, researchers must determine if the nanoparticle in this study is safe for humans, particularly children whose brains are developing. There’s also the question of how long doctors have before CP is irreversible in children. In most cases, CP is diagnosed by the age of two, but if newborns can be diagnosed and treated immediately, Kannan’s therapy would be invaluable to those young lives.

The study’s scientists already anticipate pairing the treatment with stem cell therapy to regenerate damaged nerve tissue in the brain. Not only would this help newborns with CP, but also people with other neurodegenerative diseases such as Alzheimer’s and multiple sclerosis.

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