Standing up to paraplegia with gene therapy

Elena Rugarli and colleagues from the National Neurological Institute in Milan have used gene therapy to save sensory and skeletal muscle nerve fibers from degeneration in mice with hereditary spastic paraplegia (HSP). This strategy, reported online on December 15 in advance of print publication in the January 2006 issue of the Journal of Clinical Investigation, holds promise for many other disorders characterized by nerve degeneration due to loss of function of a known gene.

Hereditary spastic paraplegia (HSP), a neurodegenerative disorder caused by progressive loss of sensory and skeletal muscle nerve fibers (axons), is characterized by weakness, spasticity, and impaired function of the lower limbs. The disorder is often due to mutations in the gene encoding the paraplegin protein. HSP sufferers are ultimately confined to a wheelchair, and currently there is no cure for the disease. In the current study, Rugarli and colleagues have shown that a one-time delivery of normal paraplegin by a viral vector to the spinal motor neurons of mice with HSP, before the onset of symptoms, was able to save axons from degeneration for up to 10 months.

Delivery of this mitochondrial energy-dependent protease improved motor function in the mice and these data show that delivery of an intracellular protein to spinal motor neurons by gene transfer may be useful not only for the treatment of HSP patients but also for those individuals with other forms of peripheral nerve damage of known genetic origin.

TITLE: Intramuscular viral delivery of paraplegin rescues peripheral axonopathy in a model of hereditary spastic paraplegia

AUTHOR CONTACT:
Elena I. Rugarli
National Neurological Institute, Milan, Italy
Phone: 39-02-23942614, Fax: 39-02-23942619, E-mail: rugarli@istituto-besta.it

View the PDF of this article at: https://www.the-jci.org/article.php?id=26210

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