Testimony on behalf of the Coalition of Heritable Disorders of Connective Tissue (CHDCT) February 17, 2010

We, the member organizations of the CHDCT are learning, as we experience the aging of the Heritable Disorders of Connective Tissue (HDCT) population, just how limited the current surgical repairs and current therapies are in protecting the health of people with these disorders. We now have the perspective to see how affected people lose their quality of life through disability due to the incurable and progressive nature of the disorders, additional surgeries and treatments are needed. We see our long-time members dying after repeated surgery has reached its limit in repairing the human body. The aging of the HDCT population has demonstrated the limits of surgical intervention and current treatments and this urges us forward in developing new technologies and finding more aggressive approaches to healing the ravages of these "wayward" mutations. Still, too many young people are dying through lack of knowledgeable diagnosis, inadequate care, and a lack of the true understanding of the complexities of these disorders. All of which mitigates for increased long-range research of HDCT.

RECOMMENDATION: We commend the Committee for its understanding, and response to, the impact of the progressive degenerative nature of the diseases of connective tissue, concern regarding current surgery and treatments, and impact on the aging population and look for additional support of HDCT research..

We represent thousands of individuals living with heritable disorders of connective tissue with a coalition of 14 advocacy and support groups, which affect in total over a million people. Heritable disorders of connective tissue are rare diseases that result from mutations in genes responsible for building tissues. Basic statistical information about these disorders is difficult to come by and unreliable at best even though disorders of connective tissue may affect over one million people in the United States. Abundant information about genes and genotypes is critical, but it is difficult to apply this information to health until robust surveillance and epidemiological information is gathered.

As we have written in our coalition testimony to Congress, progress on the translation of basic science to treatments and therapies cannot be made without correlating genotype to phenotype. The patient support groups which are members of the Coalition of Heritable Disorders of Connective Tissue (CHDCT) realize the need to understand: the incidence and prevalence of these diseases, the characteristics of these diseases, and the longitudinal progress of those diseases in various populations.

RECOMMENDATION: We urge the Committee to support the need for reliable data mandates for a registry of heritable disorders of connective tissue designed to identify the similarities and differences of these HDCT disorders, thus facilitating the work of the researcher and providing essential data.

In the past ten years, in response to the Third Workshop on Heritable Disorders of Connective Tissue (HDCT) supported by the NIAMS, that was held at NIH in November, 2000, a number of grants on HDCT were funded. These grants supported individual research projects as well as collaborative exploratory and developmental grants that investigate the cause of one or more of these disorders and novel treatment pathways. As Dr. Stephen Katz, NIAMS Director, stated in the announcement of the grant awards: "We are pleased with the quality of research that has been proposed in response to the Request for Applications," adding, "We need to understand more about these disorders and how they can be effectively treated."

RECOMMENDATION: We thank the Committee and welcome the long range strategic plans which provide an opportunity to expand future programs in support of HDCT research already in place under the heading of the Cartilage and Connective Tissue Research program and endorsed in NIH and NIAMS long range strategic plans.

Among the recommendations of the 3rd HDCT workshop for future research directives and current research interests:

· Continued use of mouse models to elucidate the sequence of events in the pathogenesis of human connective tissue disorders;

· Structure, role and interactions of extra cellular matrix molecules both inside and outside the cell;

· Role of the extra cellular matrix in cell differentiation;

· Development of therapies for connective tissue regeneration with mesenchymal stem cells.

· Importance of certain enzymes for collagen synthesis

· Role of bone marrow transplantation

RECOMMENDATION: We urge the Committee to continue to address the recommendations of the 3rd Workshop on HDCT and current promising new developments.

There have been efforts to facilitate access to information and current research of disease both for the research community and for the patient organizations, such as the CHDCT. The CHDCT is compiling documentation in support of the inclusion of HDCT as a category in the NIH Research Portfolio Online Reporting Tool (RePort) system used to categorize disease. Located within the RePort, is the RCDC, which establishes subject/ categories of disease. RCDC stands for "Research, Condition, and Disease Categorization system," and uses the categories for reporting NIH funded research, and areas of research. Currently the 215 categories, which are vitally important in providing access to this information, do not include HDCT. Therefore the category of "heritable disorders of connective tissue, (HDCT)" - which covers over 200 disorders - is a necessary category in order to expedite access by researchers to NIH funding in this area of study.

The National Institute of Health (NIH) has established the NIH RePorter, or research/condition/disease category (RCDC) which provides retrieval of information on scientific projects and studies. This excellent new tool provides information on research results, expediting access and the avoidance of duplication. But the disease group of HDCT is located under Connective Tissue Disease, and other difficult to locate subjects, which includes many unrelated to HDCT, therefore limiting the value of this important program for the research community and for the disease organizations represented within the HDCT group.

RECOMMENDATION: We commend the Committee for its support of the RePORT program, which is essential to provide coordinate access to research information on all disease groups. We also urge the inclusion of the disease group of heritable disorders of connective tissue in order to facilitate the exchange of information regarding research and the research community. At present it is difficult to track HDCT, since current RCDC key terms and concepts do not differentiate between the thousands of various connective tissue disease groups within the 215 terms of disease currently in use. The RePorter and specifically the RCDC programs should include the HDCT category of disorders as a subject heading. This subject heading is well documented as described in McKusick's Heritable Disorders of Connective Tissue, and the recently revised NIAMS informative brochure "Questions and Answers: Heritable Disorders of Connective Tissue," and as such warrant its RCDC subject heading of "HeritableDisorders of Connective Tissue."

The CHDCT has had a synergistic partnership with the American Society of Matrix Biology (ASMB). A number of conference presentations related to HDCTs have addressed subjects such as, "Fibrillin Microfibrils in Elastongenesis and Remodelling," "Mice That Lack MAGP-1 Display Subtle Connective Tissue and Bleeding Abnormalities," "Establishing Connective Tissue Pathways That Regulate Morphogenesis," and "Latent TGF-Beta Binding Proteins Orchestraters of TGF-beta Action." Sessions have focused on the genetics of connective tissue and the review of new matrix proteins and functions, which should be informative on the subject and help provide additional directions for research. The importance of meetings of this sort, besides facilitating collaboration in the research community, will be the encouragement and interest of young fellows who will be introduced to the field of connective tissue and matrix biology.

In 2005, the Pan Pacific Connective Tissue Societies Symposium included a session on HDCT, which reviewed the over ten years of investigation in the basic cause of these complex multi-system genetic disorders. The meeting utilized a creative approach to the subject focusing on new findings and the multidisciplinary approach to the question of pathogenesis of connective tissue disease. Examples of the subjects on the program are: "Transcription Factors in Development of Connective Tissue;" "Matricellular Proteins;" "Growth Factors," and the "Structure of Extracellular Matrix Molecules."

RECOMMENDATION: We commend the Committee for its support of the National Institutes of Health and NIAMS continued acknowledgement of the need for HDCT symposia and workshop meetings. Your support of the 1990; 1995; and 2000 symposia held at NIH were key to the advances which have followed this collaborative effort. This multidisciplinary approach both within NIAMS, and between the Institutes, should continue in 2010 and 2011, and further incorporate symposia and research related meetings to foster communication and research advances to promote the cross-fertilization of research. The facilitating of NIH research sharing serves to avoid wasteful duplication and provides a springboard for the future direction of research in all areas relating to these HDCT diseases.

What is so important about the study of these disorders is their very complexity. The mutations of HDCT affect all body systems and require particular depth of investigation. This very complexity informs the researcher, as well as contributes to the understanding of other more common disorders. Research on these disorders in all of the body systems, will "spill" over into research into many of the categories identified in both the short range and the long range strategic plans for NIH and NIAMS, and provides benefits for many diseases beyond the scope of HDCT. Beyond this, the goal of alleviating pain and suffering, and saving lives, remains the most important imperative to the study of HDCT.

We thank you for this opportunity to thank the Committee for its past support and to voice the interests and concerns of the CHCDT member organizations relating to future priorities of NIH and the NIAMS.

Priscilla Ciccariello
President, Coalition of Heritable Disorders of Connective Tissue (CHDCT)
Chair emeritus, National Marfan Foundation (NMF)
4301 Connecticut Avenue NW. Suite 404
Washington, DC 20008
http://www.chdct.org
(202) 966-5557 x201 (631)-725-1846

CHDCT MEMBERSHIP

CHILDREN'S BRITTLE BONE FOUNDATION
CORPORATION FOR MENKES DISEASE (CMD)
DYSTROPHIC EPIDERMOLYSIS BULLOSA RESEARCH ASSO.OF AMERICA
(DebRA)
EHLERS-DANLOS NATIONAL FOUNDATION (EDNF)
LITTLE PEOPLE OF AMERICA (LPA)
LOEYS'DIETZ FOUNDATION (LDF)
NATIONAL ASSOCIATION FOR PSEUDOXANTHOMA ELASTICUM (NAPE)
NATIONAL FOUNDATION FOR ECTODERMAL DYSPLASIAS (NFED)
NATIONAL MARFAN FOUNDATION (NMF)
OSTEOGENESIS IMPERFECTA FOUNDATION (OIF)
PXE INTERNATIONAL, INC. (PXE)
SOCIETY FOR MITRAL VALVE PROLAPSE SYNDROME (SMVP)
STICKLER INVOLVED PEOPLE(SIP)
WILLIAMS SYNDROME ASSOCIATION (WSA)

Sharon Terry, MA, Co-President,
Coalition For Heritable Disorders Of Connective Tissue
4301 Connecticut Avenue, NW, Suite 404, Washington DC 20008
Voice: 202-362-9599
Fax: 202-966-8553
E-mail: chdct@pxe.org

Priscilla Ciccariello, Co-President
cilla71@aol.com

Website: http://www.chdct.org

Copyright 2010 © Coalition For Heritable Disorders Of Connective Tissue Revised March 2010