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 $1,000,000 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

Molecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signatures

Author: J. Taroni, V. Martyanov, C. Huang, J. Mahoney, et al
Date Published: July-2015
Source: Arthritis Research & Therapy

Esophageal involvement in patients with systemic sclerosis (SSc) is common, but tissue-specific pathological mechanisms are poorly understood. There are no animal scleroderma esophagus models and esophageal smooth muscle cells dedifferentiate in culture prohibiting in vitro studies. Esophageal fibrosis is thought to disrupt smooth muscle function and lead to esophageal dilatation, but autopsy studies demonstrate esophageal smooth muscle atrophy and the absence of fibrosis in the majority of SSc cases. Herein, we perform a detailed characterization of SSc esophageal histopathology and molecular signatures at the level of gene expression.

Partially Evoked Epithelial-Mesenchymal Transition (EMT) Is Associated with Increased TGFβ Signaling within Lesional Scleroderma Skin

Author: Joanna Nikitorowicz-Buniak, Christopher P. Denton, David Abraham, Richard Stratton
Date Published: July-2015
Source: PLoS One

The origin of myofibroblasts in fibrotic conditions remains unknown and in systemic sclerosis (SSc) it has been proposed that activation of local fibroblasts, trans-differentiation of perivascular or vascular cells, recruitment of fibrocyte progenitors, or epithelial to mesenchymal transition (EMT) could be contributing. Data from our laboratory indicate that the epidermis in scleroderma is activated with the keratinocytes exhibiting a phenotype normally associated with tissue repair, including phosphorylation profiles indicative of TGFβ signaling. Since TGFβ is a known inducer of EMT, we investigated if there is evidence of this process in the SSc epidermis. In order to validate antibodies and primers, EMT was modeled in HaCaT cells cultured in the presence of TGFβ1.

Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis: a 10-year longitudinal study from the EUSTAR database

Author: E. Wirz, V. Jaeger, Y. Allanore, G. Riemekasten, E. Hachulla, O. Distler, et al
Date Published: July-2015
Source: Annals of the Rheumatic Diseases

To longitudinally map the onset and identify risk factors for skin sclerosis and digital ulcers (DUs) in patients with systemic sclerosis (SSc) from an early time point after the onset of Raynaud's phenomenon (RP) in the European Scleroderma Trials and Research (EUSTAR) cohort.

Biomarkers of pulmonary hypertension in patients with scleroderma: a case – control study

Author: Z. McMahan, F. Schoenhoff, J. Van Eyk, F. Wigley, and L. Hummers
Date Published: July-2015
Source: Arthritis Research & Therapy

Significant pulmonary vascular disease is a leading cause of death in patients with scleroderma, and early detection and early medical intervention are important, as they may delay disease progression and improve survival and quality of life. Although several biomarkers have been proposed, there remains a need to define a reliable biomarker of early pulmonary vascular disease and subsequent development of pulmonary hypertension (PH). The purpose of this study was to define potential biomarkers for clinically significant pulmonary vascular disease in patients with scleroderma.

Immunogenetics of systemic sclerosis: Defining heritability, functional variants and shared-autoimmunity pathways

Author: Lara Bossini-Castillo, Elena López-Isac, Javier Martín
Date Published: July-2015
Source: Journal of Autoimmunity

Systemic sclerosis (SSc) is a clinically heterogeneous connective tissue disorder of complex etiology. The development of large-scale genetic studies, such as genome-wide association studies (GWASs) or the Immunochip platform, has achieved remarkable progress in the knowledge of the genetic background of SSc. Herein, we provide an updated picture SSc genetic factors, offering an insight into their role in pathogenic mechanisms that characterize the disease. We review the most recent findings in the HLA region and the well-established non-HLA loci. Up to 18 non-HLA risk factors fulfilled the selected criteria and they were classified according to their role in the innate or adaptive immune response, in apoptosis, autophagy or fibrosis.

News for Patients

Enrollment Begins in Cytori U.S. Phase III/Pivotal Scleroderma Trial

 

Author: CytoriDate Published: August-2015
Source: Business Wire

Cytori Therapeutics, Inc. (NASDAQ: CYTX) today announced the launch of its U.S. phase III/pivotal trial to study the efficacy of its ECCS-50 cellular therapeutic in patients with scleroderma associated hand dysfunction. In July 2015, Cytori received follow-on U.S. FDA investigational device approval for recent updates to the Celution® System, which is being used in the STAR trial. The updates include recent technologic advances such as enhanced software code that substantially improves the efficiency of the bedside therapeutic manufacturing process for ECCS-50.

Medical nutrition therapy for patients with advanced systemic sclerosis (MNT PASS): A pilot intervention study

Author: Doerfler B, et al
Date Published: August-2015
Source: MedLinx

The objective of this study was to demonstrate the feasibility and associations with short–term outcomes of a medical nutrition therapy (MNT) intervention in patients with systemic scleroderma (SSc). Individually tailored MNT can improve symptom burden and potentially ALH in patients with SSc involving the GI tract. This study underscores the clinical potential of multidisciplinary patient management and the need for larger nutrition intervention trials of longer duration in these patients.

Autoantibody status fails to predict death risk in systemic sclerosis with PAH

Author: Lucy Piper
Date Published: August-2015
Source: News Medical

Anticentromere and isolated nucleolar autoantibodies are prevalent in systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH), but they do not predict survival, US research shows. “Our data demonstrate that although antibodies are associated with PAH development and time to PAH diagnosis, none of the SSc-specific serum autoantibodies were predictive of mortality”, report Monique Hinchcliff (Northwestern University Feinberg School of Medicine, Chicago, Illinois) and colleagues.

VTE Risk Tripled in Systemic Sclerosis

Author: Nancy Walsh
Date Published: July-2015
Source: MedPage Today

Patients with systemic sclerosis (SSc) have an overall threefold increased risk of venous thromboembolism (VTE), with the highest risks being seen during the first year after diagnosis, a Canadian population-based study found. Compared with the non-SSc population, patients with the disease had hazard ratios of 3.47 (95% CI 2.14-5.64) for VTE, 3.73 (95% CI 1.98-7.04) for pulmonary embolism (PE), and 2.96 (95% CI 1.54-5.69) for deep vein thrombosis (DVT), after adjusting for all potentially confounding variables, according to J. Antonio Avina-Zubieta, MD, PhD, of the University of British Columbia in Vancouver, and colleagues.

Women’s Immune System Genes Operate Differently From Men’s

Author: Jennie Dusheck
Date Published: July-2015
Source: Stanford Medicine

A new technology reveals that immune system genes switch on and off differently in women and men, and the source of that variation is not primarily in the DNA.A new technology for studying the human body’s vast system for toggling genes on and off reveals that genes associated with the immune system toggle more frequently, and those same genes operate differently in women and men. Some genes are virtually always on, like the clock light on a microwave; others sit unused for years at a time, like some regrettable appliance you bought, stuffed into the back of the closet and forgot. Some genes can be always on in one person and always off in another. A minority of genes switch on and off, like a favorite cell phone app. A new technology, which makes it possible to study the molecules that regulate all of that switching in living people as they go about their lives, has revealed some intriguing surprises, according to a study from the Stanford University School of Medicine.

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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