NT-3 update for our new members

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This is a repost on NT-3 for CMT 1A. We have the entire study

summary from Dr. Sahenk in our Files under " NT-3 - we also have other

NT 3 info there, plus posts back in 2002/2003 as we followed this

research on CMT 1A. In addition, please read over the information on the Vitamin

C/Ascorbic Acid research for CMT 1A in our File section.

~ Gretchen)

Neurology. 2005 Sep 13;65(5):681-9.

NT-3 promotes nerve regeneration and sensory improvement in CMT1A

mouse models and in patients.

Sahenk Z, Nagaraja HN, McCracken BS, King WM, Freimer ML, Cedarbaum

JM, Mendell JR.

Department of Neurology, Ohio State University, Columbus, OH, USA.

BACKGROUND: Xenografts from patients with Charcot-Marie-Tooth type 1A

(CMT1A) have shown delayed myelination and impaired regeneration of

nude mice axons passing through the grafted segments. Neurotrophin-3

(NT-3), an important component of the Schwann cell (SC) autocrine

survival loop, could correct these deficiencies.

OBJECTIVE: To assess the efficacy of NT-3 treatment in preclinical

studies using animal models of CMT1A and to conduct a double-blind,

placebo-controlled, randomized, pilot clinical study to assess the

efficacy of subcutaneously administered NT-3 in patients with CMT1A.

METHODS: Nude mice harboring CMT1A xenografts and Trembler(J) mice

with a peripheral myelin protein 22-point mutation were treated with

NT-3, and the myelinated fiber (MF) and SC numbers were quantitated.

Eight patients received either placebo (n = 4) or 150 microg/kg NT-3

(n = 4) three times a week for 6 months. MF regeneration in sural

nerve biopsies before and after treatment served as the primary

outcome measure. Additional endpoint measures included the Mayo

Clinic Neuropathy Impairment Score (NIS), electrophysiologic

measurements, quantitative muscle testing, and pegboard performance.

RESULTS: The NT-3 treatment augmented axonal regeneration in both

animal models. For CMT1A patients, changes in the NT-3 group were

different from those observed in the placebo group for the mean

number of small MFs within regeneration units (p = 0.0001), solitary

MFs, (p = 0.0002), and NIS (p = 0.0041). Significant improvements in

these variables were detected in the NT-3 group but not in the

placebo group. Pegboard performance was significantly worsened in the

placebo group. NT-3 was well tolerated.

CONCLUSION: Neurotrophin-3 augments nerve regeneration in animal

models for CMT1A and may benefit patients clinically, but these

results need further confirmation.