Neurodegenerative diseases such as Parkinson's, Alzheimer's and amyotrophic lateral scerlerosis (ALS) are notoriously difficult to treat because of the challenge of getting drugs across the brain-blood barrier. An article published online in Gene Therapy, describes a delivery method that uses human neural progenitor cells (hNPC) which are genetically engineered to produce GDNF - a molecule that increases the survival and functioning of dopamine-neurones and decreases symptoms of the disease.
Presently, Parkinson's disease affects 120,000 people in the UK alone. It results from the loss of the neurones that produce dopamine, a neurotransmitter involved in coordinating muscle movement. Dopamine loss leads to the archetypal symptoms of Parkinson's such as tremors, rigidity, and slowness of movement. Currently there are few drug-delivery methods that are able to get treatment into the affected parts of the brain and they are far from ideal. Some early studies with direct delivery systems for Parkinson's were effective but very complicated and require high doses of treatment. Other gene therapy treatments rely on injecting viruses into the brain that have been modified to release treatment; however this is undesirable when host cells are already sick.
Clive Svendsen and colleagues transplanted hNPCs into affected areas in rodent brains - these cells encourage fibre and cell-body outgrowth in the host neurones and increase their survival. The transplanted cells were still active three months after transplantation, say the team. The neural cells used in this delivery system confer two advantages. They have previously been shown to differentiate into new astrocytes and neurones, which also occurred in this study, but in this study the transplanted cells also migrated throughout the striatum, which allows GDNF delivery throughout this region with this method.
The authors say the GDNF-releasing cells have the potential to treat other neurological disorders. In previous work they have shown that when these engineered hNPCs are transplanted into the spinal cords of rodents with ALS they survived and had increased motor neurone enzyme activity.
Clive Svendsen (University of Wisconsin-Madison, WI, USA)
Abstract available online.
(C) Gene Therapy press release.
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