Intrathecal administration of IGF-I by AAVrh10 improves sensory and motor deficits in a mouse model of diabetic neuropathy

Molecular Therapy — Methods & Clinical Development, 2014 · DOI: 10.1038/mtm.2013.7 · Published: January 15, 2014

Simple Explanation

This research explores using gene therapy to treat diabetic peripheral neuropathy (DPN) by delivering a therapeutic gene to sensory and motor neurons. The study uses a nonhuman adeno-associated virus (AAVrh10) to deliver insulin-like growth factor (IGF-I) to the spinal cord in a mouse model of diabetic neuropathy. The results showed that AAVrh10 effectively delivered IGF-I, leading to nerve regeneration and improved nerve function in the treated mice.

Study Duration

8 weeks

Participants

Male CD-1 mice

Evidence Level

Not specified

Key Findings

1
AAVrh10 efficiently transduces both sensory neurons in the dorsal root ganglia (DRG) and motor neurons in the spinal cord after intrathecal administration.
2
Intrathecal delivery of AAVrh10 coding for IGF-I in a mouse model of diabetic neuropathy led to the release of the therapeutic protein into the cerebrospinal fluid (CSF).
3
IGF-I treatment stimulated nerve regeneration and myelination in injured limbs and restored nerve conduction velocities in both sensory and motor nerves.

Research Summary

The study demonstrates that lumbar puncture of a nonhuman AAV leads to wide and stable distribution of the vector along the spinal cord in adult mice. AAVrh10 efficiently and specifically infects neurons, both in dorsal root ganglia (60% total sensory neurons) and in the spinal cord (up to one-third of α-motor neurons). Intrathecal injection of AAVrh10 is a promising tool to design gene therapy approaches for sensorimotor diseases.

Practical Implications

Therapeutic Potential for DPN

Intrathecal AAVrh10 delivery could be a new approach for treating diabetic peripheral neuropathy by promoting nerve regeneration.

Targeted Gene Delivery

AAVrh10 shows promise for targeted gene delivery to both sensory and motor neurons in the spinal cord.

Clinical Translation

The minimally invasive intrathecal route offers a potentially safer and more effective way to deliver therapeutic genes for neurological disorders.

Study Limitations

1
Animal models of diabetes may not fully replicate human diabetic neuropathy.
2
The study focused on short-term effects and did not assess long-term safety or efficacy.
3
Cross-reaction between AAVrh10 and human AAV serotypes needs to be quantified.

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