Dendrimer-based postnatal therapy for neuroinflammation and cerebral palsy in a rabbit model.

Abstract

Cerebral palsy (CP) is a chronic childhood disorder with no effective cure. Neuroinflammation, caused by activated microglia and astrocytes, plays a key role in the pathogenesis of CP and disorders such as Alzheimer's disease and multiple sclerosis. Targeting neuroinflammation can be a potent therapeutic strategy. However, delivering drugs across the blood-brain barrier to the target cells for treating diffuse brain injury is a major challenge. We show that systemically administered polyamidoamine dendrimers localize in activated microglia and astrocytes in the brain of newborn rabbits with CP, but not healthy controls. We further demonstrate that dendrimer-based N-acetyl-l-cysteine (NAC) therapy for brain injury suppresses neuroinflammation and leads to a marked improvement in motor function in the CP kits. The well-known and safe clinical profile for NAC, when combined with dendrimer-based targeting, provides opportunities for clinical translation in the treatment of neuroinflammatory disorders in humans. The effectiveness of the dendrimer-NAC treatment, administered in the postnatal period for a prenatal insult, suggests a window of opportunity for treatment of CP in humans after birth.

• Authors: Sujatha Kannan, Hui Dai, Raghavendra S Navath, Bindu Balakrishnan, Amar Jyoti, James Janisse, Roberto Romero, Rangaramanujam M Kannan
• Journal: Science translational medicine (Sci Transl Med) Vol. 4 Issue 130 Pg. 130ra46 (Apr 18 2012) ISSN: 1946-6242 [Electronic] United States
• PMID: 22517883 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• Dendrimers
• Poly(amidoamine)
• Polyamines
• Acetylcysteine

Topics

• Acetylcysteine (therapeutic use)
• Animals
• Blood-Brain Barrier (metabolism)
• Brain (drug effects, metabolism)
• Cerebral Palsy (drug therapy)
• Dendrimers (chemistry)
• Polyamines (chemistry)
• Rabbits