hedgehog protein research update

[Guest guest]

While this research is for diabetic neuropathy, we all were following

the development of it by Curis some time ago. I am hopeful if it helps

diabetic neuropathy, it may also come to help those of us with CMT. For

background reading on the hedgehog protein, check our archives. ~

Gretchen

Hedgehog Protein May Have Therapeutic Potential for Diabetic Neuropathy

NEW YORK (Reuters Health) Feb 26 - Normal hedgehog function appears to

be disrupted in diabetic peripheral-nerve dysfunction, investigators

report. Their study findings using a rat model suggest that delivery of

exogenous hedgehog proteins may ameliorate diabetic neuropathy.

Previous work has suggested that hedgehog (Hh) proteins are involved in

the response to peripheral-nerve lesions and in their repair, Dr. Nigel

A. Calcutt and associates report in the February 14th issue of the

Journal of Clinical Investigation.

Dr. Calcutt, of the University of California at San Diego, La Jolla, and

his team observed that mRNA for desert hedgehog (DHh) is decreased in

the peripheral nerves of adult diabetic rats compared with nondiabetic

control animals.

Because sonic hedgehog (SHh) is known to be more potent than DHh, they

constructed an SHh-IgG fusion protein and injected it subcutaneously 3

times per week for 5 weeks into rats with diabetes induced 5 weeks

earlier. The injections did not affect weight loss and hyperglycemia

related to diabetes.

Untreated diabetes inhibited the progressive increase in motor-nerve and

sensory-nerve conduction velocity seen in the normal control rats over

the 10-week study period, " indicating effects on the function of large

myelinated sensory an motor fibers. " After 5 weeks of treatment with

SHh-IgG, these deficits were reversed in diabetic animals.

The diabetic state increased the proportion of medium-sized axons in the

sciatic nerve at the expense of large myelinated axons, the report

indicates, but normal morphometry was restored by the experimental

treatment.

Because diabetes-related thermal hypoalgesia was partially reduced and

levels of nerve growth factor and neuropeptides were maintained by

treatment with the fusion protein, the authors theorize that the SHg-IgG

fusion protein also protected small fibers. Medium-sized myelinated

fibers, which decrease in diabetic rats, were restored.

Dr. Eva L. Feldman, of the University of Michigan, Ann Arbor, points out

in an editorial that therapeutic efficacy in humans will be more

difficult to achieve than in animals because nerve damage is " more

chronic, extensive and severe. "

She suggests that combination therapy using hedgehog protein and

antioxidant therapy or neurotrophic support " could provide the first

effective treatment for diabetic neuropathy. "

From J Clin Invest 2003;111:431-433,507-514.