This phase I double-masked, randomized, placebo-controlled study evaluated the safety of single intravenous or subcutaneous doses of recombinant human nerve growth factor (rhNGF) in healthy human volunteers at doses ranging from 0.03 to 1 micrograms/kg. No life-threatening adverse events were seen at any dose. At doses above 0.1 microgram/kg, subjects reported mild to moderate muscle pain, primarily in the bulbar and truncal musculature. The duration and severity of these myalgias varied in a dose-dependent manner, and women appeared to be more susceptible than men. Intravenous rhNGF produced earlier and more pronounced systemic effects than did identical subcutaneous doses. Subjects receiving subcutaneous rhNGF noted hyperalgesia at the injection site, a local effect persisting up to 7 weeks, that also varied in a dose-dependent manner. Antibodies to NGF were not detected in any subject. These results indicate that systemically administered rhNGF exerts a characteristic and reproducible biological effect in healthy subjects at very low doses and in a dose-dependent manner.

Recombinant human nerve growth factor appears to be safe and shows preliminary evidence of efficacy in patients with symptomatic diabetic polyneuropathy.

We found a positive effect of recombinant human nerve growth factor on neuropathic pain and pin sensitivity in HIV-associated sensory neuropathy. rhNGF was safe and well tolerated, but injection site pain was frequent.

We enrolled and treated 122 patients with idiopathic cervical dystonia in a double-blind, placebo-controlled safety and efficacy study of botulinum toxin type B (BotB). Both A-responsive and A-resistant patients were enrolled. Patients received intramuscular injections of either BotB (2,500 U, 5,000 U, or 10,000 U) or placebo. The primary outcome measure of efficacy was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at 4 weeks following study drug administration. Secondary measures of efficacy were TWSTRS-Severity, -Disability, and -Pain subscale scores, and Analog Pain Assessment, Investigator Global Assessment, Patient Global Assessment, and Sickness Impact Profile scores. Duration of effect was estimated with an intent-to-treat analysis of responders. Safety measures included clinical parameters, laboratory tests, and adverse events. The primary and most of the secondary analyses indicated a statistically significant treatment effect and a dose response. BotB is safe, well tolerated, and efficacious in the treatment of cervical dystonia at the doses tested.

Although male gender was found to be an important risk factor for obstructive sleep apnea syndrome in both Asian and white patients, obesity may be a less significant risk factor in the Asians because the majority of our Asian patients were nonobese. There was also variability in the craniomandibular factors that contributed to obstructive sleep apnea syndrome in the two groups.