Ruboxistaurin reduces neuropathy symptoms

[Guest guest]

Biomechanics Magazine August 2007

http://www.biomech.com/showArticle.jhtml?articleID=201800342

Ruboxistaurin reduces neuropathy symptoms

By: Lori Rochelle Roniger

Ruboxistaurin increased skin microvascular blood flow (SkBF),

reduced sensory symptoms such as burning and numbness, and improved

quality of life in diabetic peripheral neuropathy patients,

according to a study published in Diabetes Care in April.

Also known as ruboxistaurin mesylate (Eli Lilly, Indianapolis), the

drug is awaiting FDA approval for diabetic retinopathy and is being

investigated as a treatment for nephropathy and other diabetic

conditions. Protein kinase C-beta overactivation is associated with

diabetic peripheral neuropathy and ruboxistaurin is an isoform-

selective PKC-beta inhibitor.

" Inhibition of the beta 2 subunit of PKC impacts positively on the

symptoms of diabetic neuropathy and has the potential to address the

underlying pathological process, " said I. Vinik, MD, PhD,

director of the Diabetes Research Institute and professor of

internal medicine at Eastern Virginia Medical School in Norfolk, and

an author of the study.

The researchers conducted a six-month randomized, double-blinded

placebo-controlled study on the effects of ruboxistaurin in 40

diabetic peripheral neuropathy patients. The participants had

diabetes type 1 or 2, bilateral sensorimotor distal peripheral

neuropathy attributed to diabetes, and an abnormal score on at least

two of the following: Neuropathy Total Symptom Score-6, vibration

detection threshold, warm thermal perception threshold, cold thermal

perception threshold, age-corrected cardiovascular reflex testing of

autonomic function, and evidence of distal symmetric polyneuropathy

based on peroneal motor nerve conduction studies.

Twenty patients received 32-mg ruboxistaurin daily and 20 received a

placebo. The groups were similar in baseline characteristics except

for their motor scores and number of insulin users (placebo: 75%,

ruboxistaurin: 30%). The subjects were an average age of 59, 80%

were male, and 82.5% had type 2 diabetes.

They were tested on various measures at baseline and after three and

six months. The researchers measured SkBF of the nondominant leg

with a laser Doppler device at basal body temperature and when the

skin was heated to 32 degrees C for 10 minutes, 40 degrees C for 10

minutes (which elicited endothelium-dependent vasodilation), and 44

degrees C for 40 minutes (which elicited C fiber-mediated

vasodilation).

They found that SkBF from the basal state to a skin temperature of

40 degrees C (endothelium-dependent SkBF) at the distal calf

increased significantly in the ruboxistaurin group from baseline to

six months (78.2%) but not in the placebo group (22.5%). However,

the results in the ruboxistaurin patients compared with those

receiving placebo were not significantly different after six months

(see figure).

The percentage increase in skin blood flow between baseline and 44

degrees C at the distal calf (C fiber-mediated SkBF) also showed a

similar trend with a significant difference between baseline and six

months in the ruboxistaurin group but no significant difference

between the two groups after six months. The researchers did not

measure any significant within- or between-group differences at the

proximal calf.

The ruboxistaurin but not placebo patients showed a significant

decrease on the Neuropathy Total Symptom Score-6, a measure of

neuropathy sensory symptoms, at both three and six months; the drop

after six months was significantly greater in the ruboxistaurin

group. On the Norfolk Quality-of-Life Questionnaire for Diabetic

Neuropathy symptom subscore, the ruboxistaurin patients underwent a

significantly greater change after six months compared with the

placebo group. The ruboxistaurin patients but not placebo patients

also demonstrated significant improvement on the test's subscore and

total score after six months.