Research Program

The best way to help people living with scleroderma is to fund the most promising research aimed at improved therapies and a cure.

Research is the cornerstone of the Scleroderma Research Foundation’s existence. Only from continued investment in top quality medical research will discoveries be made to help people living with scleroderma and improve their quality of life. To that end, we press forward with finding, funding and facilitating the most promising research projects at institutions around the world.

The Scleroderma Research Foundation (SRF) funds research aimed at understanding scleroderma pathogenesis (disease development), identifying markers for disease progression, developing new and more relevant animal models for scleroderma and developing new therapies. Through generous donations, the SRF awards research grants totaling more than $1,500,000 annually and is the largest nonprofit source of funds for scleroderma research.

Our core projects are aimed at understanding how the immune system and vasculature malfunction, how fibrosis begins and progresses as well as the interrelationships among these facets of the disease. Research relating to disease mechanisms provides a basis for identifying new therapeutic targets and the SRF actively promotes the exploration of new therapies.

The Foundation continues to focus significant energy on developing animal models that mimic aspects of scleroderma. These models will allow researchers to ask questions that cannot be asked in human studies and will complement experiments done with human tissue. Additionally, the SRF funds research aimed at identifying scleroderma biomarkers. Effective biomarkers could be used for early diagnosis, predicting and monitoring disease progression and assessing response to therapies.

The Scleroderma Research Foundation is dedicated to fostering the creation and continued success of Scleroderma Clinical Centers of Excellence. At these Centers, physicians representing many different specialties, such as rheumatology, pulmonology, cardiology, gastroenterology and dermatology are dedicated to clinical research and the care of scleroderma patients. Patients receive integrated care at the Centers and because all of the specialists are present and work closely together, standards of scleroderma care can be advanced. The Centers are also critical for training the next generation of scleroderma physicians and clinical investigators. Physicians and clinical investigators at the Centers play an integral role in other research projects funded by the SRF by providing vital clinical expertise.

With the expert guidance of our esteemed Scientific Advisory Board, our research projects are evaluated annually at the SRF Scientific Workshop, where intensive review and discussion of the next critical steps take place. The workshop is a forum for leading scientists from inside and outside the SRF program to provide new perspectives on the search for a cure, while promoting synergy among investigators and advancing the growing understanding of scleroderma.

Understanding of scleroderma at the cellular and molecular level is increasing thanks in part to partnerships the SRF has facilitated. Increasingly, SRF-funded scientists are exploring new opportunities that will translate laboratory advances into effective therapies to help patients live longer, fuller lives.

The Scleroderma Research Foundation is leading the scleroderma research effort by:

  • Promoting collaboration and cross-institutional cooperation among scientists in a variety of disciplines, through a strategic, integrated program.
  • Attracting promising new scientists to scleroderma research, through its Postdoctoral Fellowship Program.
  • Promoting and maintaining Scleroderma Centers of Excellence, such as the Scleroderma Center at Johns Hopkins University.
  • Bringing new experts, technology and forward thinking to the field of scleroderma research.
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Research News

Platelets induce thymic stromal lymphopoietin production by endothelial cells: Contribution to human systemic sclerosis fibrosis

Author: Marie-Elise Truchetet MD-PhD1, Béatrice Demoures, Jorge E. Guimaraes, Anne Bertrand, Paôline Laurent1, Valérie Jolivel1, et al
Date Published: July-2016
Source: Arthritis & Rheumatology

Objective To investigate the relationship between vascular damage and fibrosis in systemic sclerosis (SSc), we tested the hypothesis that platelets contribute to skin fibrosis via the activation of dermal microvascular endothelial cells and subsequent production of pro-fibrotic mediators.

Methods A total of 203 SSc patients and 30 healthy donors (HDs) were prospectively enrolled between 2012 and 2015 at the University Hospital of Bordeaux. Immunohistochemistry and immunofluorescence analyses were performed on skin biopsies from 18 SSc patients and 5 HDs. Serum TSLP levels were measured (ELISA) in the entire cohort. Human dermal microvascular endothelial cells and fibroblasts were purified from biopsies. Extracellular matrix production by cultured fibroblasts was assessed by RT-qPCR.

Systemic sclerosis: The need for structured care

Author: Kathleen Morrisroe, Tracy Frech, Janine Schniering, Britta Maurer, Mandana Nikpour
Date Published: July-2016
Source: Clinical Rheumatology

Autoimmune connective tissue diseases (CTDs) have a propensity to affect multiple organ systems as well as physical function, quality of life, and survival. Their clinical heterogeneity, multisystem involvement, and low worldwide prevalence present challenges for researchers to establish a study design to help better understand the course and outcomes of CTDs.

Systemic sclerosis (SSc) is a notable example of a CTD, wherein longitudinal cohort studies (LCS) have enabled us to elucidate disease manifestations, disease course, and risk and prognostic factors for clinically important outcomes, by embedding research in clinical practice. Nevertheless, further efforts are needed to better understand SSc especially with regard to recognizing organ involvement early, developing new therapies, optimizing the use of existing therapies, and defining treatment targets.

Structural organization of the inactive X chromosome in the mouse

Author: Luca Giorgetti, Bryan R. Lajoie, Ava C. Carter, Mikael Attia, Ye Zhan, Jin Xu, Chong Jian Chen, Noam Kaplan, Howard Y. Chang, Edith Heard & Job Dekker
Date Published: July-2016
Source: Nature

X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region1, 2, although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts3. A role for Xist in organizing the inactive X (Xi) chromosome has been proposed4, 5, 6. Recent chromosome conformation capture approaches have revealed global loss of local structure on the Xi chromosome and formation of large mega-domains, separated by a region containing the DXZ4 macrosatellite.

An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Scleroderma-associated Interstitial Lung Disease: the LOTUSS Trial

Author: Dinesh Khanna, Carlo Albera, Aryeh Fischer, Nader Khalidi, Ganesh Raghu, Lorinda Chung, Dan Chen, Elena Schiopu, Margit Tagliaferri, James R. Seiboldand Eduard Gorina
Date Published: June-2016
Source: The Journal of Rheumatology

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) shares a number of clinical features and pathogenic mechanisms with idiopathic pulmonary fibrosis (IPF). This study was designed to evaluate the tolerability of the IPF treatment pirfenidone in SSc-ILD. The known gastrointestinal, skin, and liver adverse events (AE) of pirfenidone are of importance given the involvement of these organs in SSc.

Clinical characteristics and predictors of gangrene in patients with systemic sclerosis and digital ulcers in the Digital Ulcer Outcome Registry: a prospective, observational cohort

Author: Daniel Rosenberg, Barbara Schwierin and Marco Matucci-Cerinic Yannick Allanore, Christopher P Denton, Thomas Krieg, Peter Cornelisse
Date Published: June-2016
Source: Annals of the Rheumatic Diseases

Digital vasculopathy in systemic sclerosis (SSc) consists of a spectrum of Raynaud’s phenomenon (RP), digital ulcers (DUs), critical digital ischaemia and escalation to gangrene. The complications of severe digital vasculopathy often require hospital-based management with intravenous therapies and surgery.1–3 Although gangrene is not infrequent in the clinic, data on the prevalence and implications of gangrene in patients with SSc are scarce.

News for Patients

Adempas PAH Benefits Extend to SSc

Author: Nancy Walsh
Date Published: July-2016
Source: MedPage Today

Treatment with riociguat (Adempas) increased exercise capacity among patients whose pulmonary arterial hypertension was associated with connective tissue disease (PAH-CTD) in a post-hoc analysis of a phase III clinical trial, researchers reported.

Among PAH-CTD patients randomized to receive riociguat in dosages up to 2.5 mg three times per day, the mean 6-minute walking distance increased by 18 meters at week 12 compared with a decrease of 8 m (about 26 ft.) for those given placebo, for a mean treatment difference of +28 m (95% CI -4 to 61), according to Christopher P. Denton, MD, of University College London, and colleagues.

Digital ulcers in systemic sclerosis

Author: Christopher P. Denton
Date Published: July-2016
Source: The Lancet

Systemic sclerosis (scleroderma) is one of the most recalcitrant of the immune-mediated rheumatic diseases because of its clinical impact and the high mortality associated with the internal organ complications that it causes.1 Lung fibrosis has emerged as a major cause of scleroderma-related death, and with better treatments for pulmonary arterial hypertension, the other main lethal lung manifestation of scleroderma, this looks set to continue.

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial

Author: D.P. Tashkin, MD, M.D. Roth, MD, P.J. Clements, MD, D.E. Furst, MD, D. Khanna, MD, E.C. Kleerup, MD, J. Goldin, MD, E. Arriola, PharmD, E.R. Volkmann, MD, et al
Date Published: July-2016
Source: The Lancet

12 months of oral cyclophosphamide has been shown to alter the progression of scleroderma-related interstitial lung disease when compared with placebo. However, toxicity was a concern and without continued treatment the efficacy disappeared by 24 months. We hypothesised that a 2 year course of mycophenolate mofetil would be safer, better tolerated, and produce longer lasting improvements than cyclophosphamide.

Taking it personally, cutting-edge biotech snags $45 million

Author: Ron Leuty
Date Published: July-2016
Source: San Francisco Business Times

This year-old company is taking on fibrotic diseases — and it's a personal battle.

Advanced Echo Detection of Heart Disease in Scleroderma

Author: Johns Hopkins Rheumatology
Date Published: July-2016
Source: Johns Hopkins Medicine

A new imaging technique reveals evidence of heart dysfunction in Scleroderma patients with undiagnosed heart disease. In a team effort between the Johns Hopkins Divisions of Rheumatology, Cardiology, and Pulmonary/Critical Care Medicine, led by Monica Mukherjee, M.D. and Ami A. Shah, M.D., researchers coupled traditional echocardiography (echo) with a new technique called “speckle-tracking” to reveal the presence of right heart dysfunction that was not detected by traditional methods. This new method may identify patients with Scleroderma who are at high risk for developing disability and even death due to severe heart disease.

Ways to Give

There are many ways that you can support the work of the Scleroderma Research Foundation. We are grateful for your commitment to helping the SRF fund research that will result in improved therapies and, ultimately, a cure.

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