Gene therapy using nanotubes enables functional recovery in stroke
Stroke is the second most common cause of death worldwide with over 80% of all stroke cases occurring as a result of an obstruction within a blood vessel supplying blood to the brain. Ischemic or traumatic brain injury can lead to the unwanted activation of a protein, caspase 3, which contributes to brain tissue loss. This "executioner" protein can be "switched off" through the use of siRNA - a molecule that obstructs the expression of genes. The challenge of delivering siRNA in sufficient quantities to specific brain regions was achieved through the use of nanotubes injected directly into the brain by high precision neurosurgical techniques.
These extraordinary nanometer-scale tubes of graphitic carbon are among the stiffest and strongest fibres known and have a structure that can have a length to- diameter ratio as large as 28,000,000:1. Similar to a syringe at the nanometer scale, nanotubes were used to transport siRNA and silence genes in the brain in an effective manner. A combination of this promising gene therapy approach with a cutting-edge nanoscale delivery system was able to demonstrate functional recovery in stroke-ridden animals.
Nanotubes carrying siRNA against Caspase-3 were injected in the part of cerebral cortex controlling the movement of the forelimb and stroke was induced in the treated cortex. The authors found that the treatment protected neuronal cells from death and promoted recovery in a behavioural test of motor coordination that is normally affected by this type of lesion. A similar dose of siRNA administered alone, without nanotubes, was not effective on neuronal death or motor performance indicating that nanotubes were responsible for the activity and functional recovery obtained.
Professor Kostas Kostarelos, Chair of Nanomedicine and Head of the Centre for Drug Delivery Research said:
''We are delighted to see carbon nanotubes offer therapeutic options at the pre-clinical level, for debilitating and extremely challenging to intervene pathologies such as stroke. Still at very early stages towards their clinical development, carbon nanomaterials encourage us with their capabilities to transport biologically-active molecules intracellularly, even in the notoriously difficult to transfect neuronal tissue''.
The work was led by the Nanomedicine Lab at The School of Pharmacy, University of London and the Neuroscience Institute at the National Research Centre (CNR) in Pisa, Italy. It was supported partly by various European Commission FP6 and FP7 research grants and partly by an EPSRC 'Nanotechnology Grand Challenges: Healthcare' grant to Professor Kostarelos.
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