BETHESDA, MD (NIH) -- Ten new research grants on scleroderma (systemic sclerosis) have been funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health (NIH). The grants, totaling more than $2 million per year, include both basic and clinical research studies. The Office of Research on Women's Health (ORWH) co-funded two of the grants.

"These research grants will provide new clues to understanding this disease, which is an important step towards prevention and cure," said Stephen I. Katz, M.D., Ph.D., director of the NIAMS. "The grants complement our already considerable investment in scleroderma research, which includes support of two specialized centers of research on the disease, as well as the recent funding of a Multidisciplinary Clinical Research Center on pediatric rheumatic diseases, such as juvenile scleroderma."

Scleroderma, often referred to as a single disease, is actually a symptom of a group of diseases that involves the abnormal growth of connective tissue, which supports the skin and internal organs. In some forms of scleroderma, hard, tight skin is the extent of the disease. In other forms, however, the problem goes much deeper, affecting blood vessels and internal organs, such as heart, lungs, and kidneys. In scleroderma, the immune system is thought to stimulate cells called fibroblasts to produce excess collagen.

Currently, there is no treatment that controls or stops the underlying problem: the overproduction of collagen. Little is known about the cellular changes that cause the skin and organs to harden, and the disease may be difficult to diagnose. Understanding the early cellular and molecular changes in scleroderma will help scientists to develop more effective treatments. The following projects will increase our understanding of the causes of scleroderma and bring us closer to finding treatments:

Cellular And Molecular Processes In Scleroderma

"Immune Recognition of Modified Antigen in Scleroderma", Robert W. Hoffman, M.D., University of Missouri, Columbia. This study investigates the biochemistry of a characteristic autoantibody seen in scleroderma.

"The Molecular Basis for Endothelial Dysfunction in Systemic Sclerosis", Bashar Kahaleh, M.D., Medical College of Ohio at Toledo. Small blood vessel abnormalities are seen in early scleroderma. This project investigates molecular and cellular mechanisms that may cause this dysfunction.

"Fine Specificity of Scleroderma Autoantibodies", Judith A. James, M.D., Oklahoma Medical Research Foundation, Oklahoma City. This study examines the autoantibodies and where they bind in the tissue to determine their role in the development of scleroderma. (Co-funded by ORWH)

"Study of Persistent Infection in Systemic Sclerosis Skin and Vessels", Maureen D. Mayes, M.D., Wayne State University, Detroit. This project examines persistent bacterial infection of the skin or small blood vessels as a potential cause of scleroderma. Results could lead to treatments that target the bacterial infection.

"Studies of Collagen Gene Regulation in Two Murine Models of Scleroderma", Stephen H. Clark, Ph.D., University of Connecticut School of Medicine and Dentistry, Farmington. This project uses two mouse models to better understand the molecular mechanisms that increase accumulation of collagen in the skin characteristic of scleroderma. (Co-funded by ORWH)

"Self- and Foreign-Lipids Presented by CD1 in Scleroderma", Michael S. Vincent, M.D., Brigham and Women's Hospital, Boston. This study investigates the interactions of CD1 proteins and T cells in the development of scleroderma.

Cell Transfer Between Mother And Child And Scleroderma

"HLA Alleles, Self-Peptides and Microbial Mimicry in Systemic Sclerosis", J. Lee Nelson, M.D., Fred Hutchinson Cancer Research Center, Seattle. Blood cells move between mother and child during pregnancy and may remain in either or both. This project studies blood cells from scleroderma patients and controls to determine their origin and role in the development of scleroderma.

"T Cells in the Pathogenesis of Systemic Sclerosis", Chris D. Platsoucas, Ph.D., Temple University, Philadelphia. Later in life, maternal immune cells can be found in the child and fetal immune cells in the mother. This study will investigate the origin and role of these immune cells in the skin of scleroderma patients.

Research Projects On Innovative Therapies For Scleroderma:

"Chemokine Antagonists in a Murine Model for Scleroderma", Anita C. Gilliam, M.D., Case Western Reserve University, Cleveland. This project uses a mouse model to study the early inflammatory events of skin fibrosis. This research will facilitate the early diagnosis of scleroderma so that treatment can be more effective. The mouse model allows investigators to test inhibitors to inflammation in animals before testing them in humans.

"UV-Induced Collagen Reduction for Treating Skin Scleroderma", Sewon Kang, M.D., University of Michigan at Ann Arbor. This study tests the effectiveness of UV phototherapy for the treatment of localized forms of scleroderma.

The award of these grants is the result of the special solicitation for research applications on scleroderma, AR- 00-007 entitled "Molecular Pathogenesis and New Interventions in Scleroderma" (http://www.niams.nih.gov/rtac/funding/grants/rfa/ar00- 007.htm). This RFA was based in part on the scientific opportunities identified in the conference cosponsored by NIAMS, "Emerging Opportunities in Scleroderma Research." A summary of the conference can be found at http://www.niams.nih.gov/ne/reports/sci_wrk/1997/sclersum.h tm.