New Understanding of Skin Hardening Syndromes Found PDF Print E-mail
Thursday, 19 May 2011 09:52
New details about the underlying mechanisms of skin hardening syndromes, morphea, have been discovered by researchers from Boston University School of Medicine (BUSM). Morphea, also known as localized scleroderma, is a disorder characterized by excessive collagen deposition leading to thickening of the dermis, subcutaneous tissues, or both.

Thomas Ruenger, MD, PhD, a professor and vice-chair of dermatology at BUSM, and colleagues connected pharmacological properties of the Novartis Pharma AG drug called balicatib to the skin disorder for the first time after investigating adverse reactions suffered by patients participating in a clinical trial for the treatment of osteoporosis. The team’s findings appear online in the Journal of the American Academy of Dermatology.

Morphea is rare. The estimated incidence is approximately 25 cases per million population per year. Drug-induced morphea is even rarer as noted by Oliver Kraigher, MD and colleagues in their 2009 Archives of Dermatology article, “To our knowledge, only 10 cases of drug-associated morphea have been reported, induced by vitamin K1 (phytonadione), vitamin B12 (cyanocobalamin), penicillamine, bromocriptine, pentazocine, 5-hydroxytryptophan/carbidopa combination, and balicatib. In half of these cases, partial or complete response was achieved after the drug treatment was stopped.”

Balicatib was developed recently as an osteoporosis drug that can inhibit CathepsinK (catK), an enzyme involved with bone degradation. A phase II study of balicatib in women with postmenopausal osteoporosis showed dose-dependent reduction in levels of bone resorptive markers and an increase in bone mineral density, but a small number of patients developed morphealike skin changes.

Most of the patients in the balicatib trial who experienced the morphea skin changes did so in the neck, chest and abdomen regions.

Balicatib is lysosomotropic and can accumulate in lysosomes with a high enough concentration to cause off-target inhibition of other types of cathepsins, some of which are expressed by skin fibroblasts.

After examining the cases and relating them to recent reports of cathepsin K expression in the skin and the role of cathepsin K in degrading collagen and elastin, the investigators determined that the changes were a direct effect of the drug.

This case study proves that catK affects the skin as well as bones, and marks the first time that skin hardening can be convincingly linked to the pharmacologic properties of a drug.

"This observation emphasizes the importance of intracellular collagen degradation in the skin, a pathway so far vastly underappreciated," said Thomas Ruenger, MD, PhD, a professor and vice-chair of dermatology at BUSM. "This observation also sheds new light on our understanding of the mechanisms involved in morphea, or skin hardening. Failed collagen degradation has so far not been thought to cause morphea."

The researchers believe these findings have far-reaching implications for osteoporosis patients and those suffering from skin hardening syndromes.

Source: Bates, R. (2011), "New Understanding of Skin Hardening Syndromes Found"; source article can be viewed here.
 
More articles :

» New Research Findings May Bring Breakthrough For Scleroderma Patients

Research presented at the European Academy of Dermatology and Venereology in Prague, Czech Republic, suggests that inhibition of the may be a viable therapeutic target in patients.This finding builds on previous research by presenter and lead...

» Scleroderma Patients At Greater Risk Of Myocardial Infarction Within First Year

According to the first large population-based cohort study of its kind, patients with Systemic Sclerosis or were found to be at a greater than eightfold increased risk of having an acute (MI) during their first year after diagnosis. After that...

» Positive Phase II Results for AIMSPRO In Scleroderma Announced

announced yesterday, positive results from its Double-Blind Placebo-Controlled Phase II Clinical Study evaluating the safety and tolerability of AIMSPRO given as a monotherapy to patients with Late Stage Established Diffuse Cutaneous Systemic...

» A Call For Better Monitoring and Treatment Of Scleroderma Patients

The New Zealand Scleroderma Group is calling for the introduction of a monitoring and treatment programme for New Zealanders with scleroderma to mark World Scleroderma Day on June 29.Scleroderma is an autoimmune connective tissue disease that can...

» Researchers Identify Core Genetic Switch As A Viable Target For New Scleroderma Treatments

Scleroderma is a rare, autoimmune disease. Often fatal, it causes the fibrosis or thickening of the connective tissue which support the skin and other vital organs within the body, through the overproduction of . The disease currently lacks a cure...

» UTHealth, Fudan University Launch Scleroderma Network

Scleroderma clinicians and researchers in the United States and China have launched an international network to fight this debilitating disease that affects more than one million people worldwide.The network was established by faculty at The...