Question by Kevin7: can a nanotechnology based drug greatly reduce Cerebral palsy symptoms in rabbits?
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Window of Opportunity to Prevent Cerebral Palsy Discovered: Nanodrugs Work in Newborn Rabbits
ScienceDaily (Apr. 18, 2012) — Researchers at the Perinatology Research Branch of the National Institutes of Health, housed at the Wayne State University School of Medicine and the Detroit Medical Center, have demonstrated that a nanotechnology-based drug treatment in newborn rabbits with cerebral palsy enabled dramatic improvement of movement disorders and the inflammatory process of the brain that causes many cases of CP. The findings strongly suggest that there may be an opportunity immediately after birth for drug treatment that could minimize CP.
The study is the first to show that an anti-inflammatory drug delivered with a nanodevice can dramatically improve CP symptoms in an animal model.
The report, “Dendrimer-Based Postnatal Therapy for Neuroinflammation and Cerebral Palsy in a Rabbit Model,” was published April 18 in the journal Science Translational Medicine, published by the American Association for the Advancement of Science.
“The key finding of this work is that early identification of neuroinflammation allows postnatal treatment,” said Roberto Romero, M.D., D.Med.Sci., chief of the Perinatology Research Branch and an author of the study. “This suggests that there is a window of opportunity to prevent cerebral palsy.”
The PRB team hypothesized that it was possible to deliver a drug using a tiny device (or nanodevice) that would cross the blood-brain barrier and target the activated cells (microglia and astrocytes) in the brain involved in neuroinflammation.
The researchers used a rabbit model of congenital CP because it replicates the type of neuroinflammation found in human brains and the resulting motor deficits observed in children with the condition. The method consisted of exposing fetal rabbits to endotoxin (a component of bacteria). Endotoxin induced inflammation of the fetal brain but did not induce the onset of labor. When the rabbits were born, they had great difficulties walking or hopping. The experiment consisted of treating affected rabbits intravenously with either a saline solution, a drug known as NAC (N-acetyl-L-cysteine) or a dendrímer coupled with NAC, also known as a D-NAC conjugate. Rabbits with CP treated with D-NAC on the first day of life showed a dramatic improvement and, within five days, were able to walk and hop. Rabbits treated with the NAC conjugate also showed a higher neuron count and lower evidence of inflammation compared to untreated animals.
NAC is an antioxidant and anti-inflammatory agent. It is being explored in several ongoing clinical trials to test its potential in autism spectrum disorders, pregnant women for the treatment of maternal and fetal inflammation, and Alzheimer’s disease. Dendrimers are synthetic biomimics of globular polymers of the amino acid alanine. Researchers are exploring their use as a vehicle to target drug delivery, a science known as nanotechnology.
The authors believe that conjugating NAC with dendrimers allows delivery of the drug directly to the cells involved, providing greater effectiveness.
“One of the challenges of the 21st century is to rebuild brains injured during fetal or neonatal life, and to prevent not only cerebral palsy, but also other brain disorders,” Dr. Romero said.
While still in preclinical testing in animals, the dendrimer-drug conjugate shows promise for postnatal treatment of babies suspected of having CP.
“This is an exciting breakthrough and it certainly points toward new hope for those affected by cerebral palsy,” said Rangaramanujam M. Kannan, Ph.D., a chemical engineer and a member of the PRB research team and an author of the study. “We found that the administration of the anti-inflammatory agent coupled with the dendrimers allowed the drug to not only cross the blood-brain barrier but also to target the cells that cause the neuroinflammation in CP. Of course, this approach and these compounds are not yet approved for testing in humans, and further studies are required to find the optimal dose, duration of treatment and establish safety. More questions need to be answered, but the potential is immense.”
“The use of a rabbit model is a unique aspect of the work, since this model mimics the phenotype of CP as seen in humans. This also illustrates the potential of research collaborations across disciplines in advancing and translating novel technologies for the treatment of debilitating childhood disorders,” said Dr. Sujatha Kannan, a pediatrician and first author of the study.
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