peripheral neuropathies: the therapeutic potential of gene transfer

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Expert Rev Mol Med. 2007 Mar 19;9(8):1-20.

The therapeutic potential of gene transfer for the treatment of

peripheral neuropathies.

Goss JR.

Peripheral neuropathy is a common medical problem with numerous

aetiologies. Unfortunately, for the majority of cases there is no

available medical solution for the underlying cause, and the only

option is to try to treat the resulting symptoms. Treatment options

exist when neuropathy results in positive symptoms such as pain, but

there is a significant lack of treatments for negative symptoms such

as numbness and weakness.

Systemic application of growth factor peptides has shown promise in

protecting nerves from neuropathic insults in preclinical animal

studies, but translation into human trials has been problematic and

disappointing. Significant advancements have been made in the past

few years in utilising gene therapy approaches to treat peripheral

neuropathy by expressing neuroprotective gene products either

systemically or in specific nervous tissues.

For example, plasmids expressing vascular endothelial growth factor

injected into muscle, or herpes-simplex-virus-based vectors

expressing neurotrophin gene products delivered to dorsal root

ganglion neurons, have been used to protect peripheral nerve

function in animal models of diabetes-associated peripheral

neuropathy.

Many published studies support the feasibility of this approach,

although several questions still need to be addressed as gene

therapy to treat peripheral neuropathy moves out of the laboratory

and into the clinic.