Significant Items in House, Senate, and Conference Appropriations Committee Reports
FY 2005 Budget

February 2004 (historical)

FY 2004 House Appropriations Committee Report Language (H. Rpt. 108-188)

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Lupus - The Committee encourages NIAMS to enhance its research efforts on lupus through all available means, as appropriate, to improve understanding of the disease and lead to advances in treatment. There are five areas in which research may yield important new insights, including susceptibility, pathogenesis, inflammation and damage, clinical assessment and therapy. In addition, the Committee encourages NIAMS to facilitate efforts to validate biomarkers for lupus. In recent years, the lupus research community has identified a number of biologic molecules that may serve as effective markers of disease risk, disease activity or severity, clinical features of the disease, or response to potential therapies. Collaborative approaches to research on biomarkers could lead to the development of promising new drugs, and ease the way to approval of these agents by the FDA. (p. 79)

Action taken or to be taken

The NIAMS is enhancing its research activities in lupus through a multitude of efforts. Several recent NIAMS-funded research discoveries have significant implications for the clinical assessment and treatment of lupus. For example, a team of scientists supported by NIAMS and other components of the NIH - including the National Institute of Allergy and Infectious Diseases, the National Center on Minority Health and Health Disparities, and the Office of Research on Women's Health - discovered a genetic "signature" present in some patients with lupus who develop life-threatening complications such as blood disorders, central nervous system damage, and kidney failure. After analyzing thousands of genes in the blood of patients with lupus, researchers found 14 of those genes were linked to a subset of lupus patients with severe disease. These findings provide strong support for developing new therapies to block the affected pathways in patients with severe lupus, as well as for identifying patients most likely to benefit from these new therapies. Another research highlight was the recent discovery that people diagnosed with lupus have autoantibodies (proteins that attach to the body's healthy tissue by mistake) in their blood years before the symptoms of lupus appear. Early detection of autoantibodies may help in predicting who will develop this disease, as well as allowing physicians to monitor patients earlier in the disease process. In the area of childhood lupus, the NIAMS recently initiated a large, controlled study to assess the ability of statins (cholesterol-lowering agents) in preventing or delaying progression of cardiovascular disease in children with lupus. This research study involves 20 centers from the Pediatric Rheumatology Research Network in establishing the largest cohort of pediatric lupus patients ever prospectively studied.

The Institute is also actively supporting research to identify and validate biomarkers for lupus. For example, the Institute's extramural program supports the Autoimmune Biomarkers Collaborative Network, a group that is using cutting edge technologies, such as gene expression profiling with DNA microarrays, to develop biomarkers for lupus. These new technologies may assist in the diagnosis of lupus, help physicians better guide and manage therapy, and provide information on the course of disease for lupus patients. In the fall of 2003, the NIAMS intramural program held a meeting with experts from the lupus research community to discuss how to establish new strategies for developing and validating biomarkers for lupus. These biomarkers will be used in clinical settings to facilitate the process of making new therapies available to patients. Participants included clinical and basic scientists from the lupus research community, as well as representatives of the NIH, the Food and Drug Administration, and voluntary organizations.

The NIAMS is also enhancing research efforts on lupus through a new Federal Working Group on Lupus, the purpose of which is to exchange information and coordinate Federal efforts in lupus research and education. This group complements the NIH Autoimmune Diseases Coordinating Committee (ADCC) which recently developed a comprehensive research plan for autoimmune diseases, including lupus. The new Lupus Working Group is comprised of representatives from all relevant DHHS agencies and other Federal departments having an interest in lupus. The NIAMS was chosen to lead this new Working Group, which held its first meeting in the fall of 2003.

Also in the fall of 2003, national leaders in lupus research came together to discuss the latest scientific opportunities at the "Lupus Today: Research Into Action" scientific conference. As a co-sponsor for this conference, the NIAMS invited leading lupus researchers to gather to discuss the latest scientific discoveries and what they mean for the current and future management of lupus. Panel discussions included: the future of lupus clinical trials, patient participation in clinical trials, and how lupus affects minority populations. Other topics covered at the conference included childhood lupus, cardiovascular lupus, and neuropsychiatric lupus. Information on cutting edge clinical trials involving stem cell therapy and high dose cytoxan was also presented.

Lupus is a key area in the NIAMS' focus on health disparities. The Institute's Health Partnership Program is working with community leaders and organizations in the African American and Hispanic/Latino communities in Washington, D.C., to develop a model community-based initiative for addressing disparities in rheumatic diseases, including lupus. In addition, the Institute recently released a solicitation for applications on innovative approaches to eliminating health disparities in rheumatic, musculoskeletal, and skin diseases. This solicitation will encourage the development of new approaches to addressing the high prevalence of rheumatic diseases such as lupus in minority populations.

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Bone diseases - The Committee urges NIAMS to explore new avenues for cell- and gene-based therapies for the treatment of bone and cartilage diseases, such as osteoporosis, Paget's disease, and osteogenesis imperfecta, as well as identify new targets for enhancing bone formation and blocking bone destruction. (p. 79)

Action taken or to be taken

Stem cell research is an area of cutting edge scientific inquiry that provides new opportunities for researchers and clinicians working in a variety of fields. In June 2000, the NIAMS and the National Institute on Aging held a workshop to identify new opportunities in basic and applied stem cell research, and to promote the orderly and optimal development of the field and the development and use of therapeutic interventions. As a result of this meeting, NIAMS issued a request for applications (RFA) aimed at exploring basic and applied stem cell research for arthritis and musculoskeletal diseases. In 2002, NIAMS announced the funding of five new projects in response to this solicitation, including several that have important implications for bone and cartilage diseases such as osteoporosis, Paget's disease, and osteogenesis imperfecta (OI). These studies include work to better understand the growth factors and hormones that influence how stem cells develop, which could point the way to new therapies for bone diseases; efforts to evaluate the potential for regeneration or repair of bone marrow using mouse stem cells in an animal model of OI; and investigations of programmed cell death and how that process generates a form of stem cells that are a factor in maintaining adult bone mass.

Current research in Paget's disease and other areas across bone research will facilitate the development of cell- and gene-based treatments for many disorders. For example, NIAMS continues to support a number of projects investigating the viral and genetic factors contributing to Paget's disease, including a multi-component research program aimed at understanding the causes of Paget's disease. Four related projects, integrated within a single program, will examine several factors that contribute to the development of the disease. A key component is the creation of a new strain of mice, based on the long-suspected role of measles virus infection in Paget's disease, that exhibits bone abnormalities resembling the human disease. Additionally, in October 2003, the NIAMS collaborated with the NIH Office of Rare Diseases and the National Institute of Diabetes and Digestive and Kidney Diseases to sponsor the First International Symposium on Osteopetrosis, a condition present at birth in which the bones are overly dense. At this Symposium, recent findings were presented, identifying the genetic defects that cause most instances of this disease. Such information will be crucial in developing new cell- and gene-based therapies for osteopetrosis, which arises from defects in the cells that normally remove old cartilage and bone as the skeleton grows.

Known as "brittle bone disease," OI arises from mutations in the two genes that make type I collagen, a protein important to bones and skin. The mutations can cause the body to make either too little or poor-quality type I collagen. Individuals with OI have bones that fracture easily, low muscle mass, and joint and ligament laxity. In the Fall of 2000, NIAMS partnered with the National Institute on Aging and the National Institute of Child Health and Human Development and released a request for applications (RFA) entitled "New Research Strategies in Osteogenesis Imperfecta." This RFA was built on recommendations that were made at the scientific meeting in September of 1999 that was co-sponsored by the NIAMS, the NIH Office of Rare Diseases, the Osteogenesis Imperfecta Foundation, and the Children's Brittle Bone Foundation, to identify ways to expand the scope of research on OI. NIAMS announced the funding of four new projects in response to this solicitation to support research activities ranging from cutting-edge gene and cell therapies to testing drug treatments in animal models. NIAMS also partnered with the National Heart, Lung, and Blood Institute in early 2002 to issue an RFA entitled "Research on Heritable Disorders of Connective Tissue." This RFA was designed to stimulate research to better understand the disease progression of heritable disorders of connective tissue, such as OI, and to develop innovative treatment strategies. In the fall of 2002, the NIAMS announced the funding of eight new projects in response to this solicitation, including several that may have implications for OI. These new projects will complement on-going work on OI.

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Duchenne muscular dystrophy - Duchenne is a degenerative and fatal form of muscular dystrophy that usually takes its victims in their late teens or early twenties. The only treatment is the long-term use of steroids, which delays the progression of the disease but has many unwanted side effects. The Committee considers this a very important area of research and urges NIAMS, along with NINDS and NICHD, to work to enhance the research efforts into Duchenne muscular dystrophy. (p. 79)

Action taken or to be taken

The NIH has been actively engaged in implementing the Muscular Dystrophy Community Assistance, Research, and Education Amendments of 2001 (the MD-CARE Act), to boost research and training related to all forms of muscular dystrophy, including Duchenne MD. In September 2002, NIH issued a request for applications (RFA) entitled "Muscular Dystrophy Cooperative Research Centers," and in October 2003, following peer review of the submitted applications, NIH announced plans to establish three new centers. NIAMS, NICHD, and NINDS are each funding one center at up to $1 million in direct costs per center per year for five years. The centers are based at the University of Pittsburgh (funded by NIAMS); the University of Washington, Seattle (funded by NICHD); and the University of Rochester, New York (funded by NINDS). Researchers at the three centers will conduct studies on Duchenne, myotonic, and facioscapulohumeral muscular dystrophies, and will investigate therapeutic approaches including stem cell and gene therapy. In fiscal year (FY) 2004, NIH plans to re-issue the solicitation for cooperative research centers, and expects to fund up to two additional meritorious centers in FY 2005.

In a novel collaboration, the Muscular Dystrophy Association (MDA) has agreed to commit up to $1.5 million to enhance research activities at each of the three Centers funded by NIH ($500,000 per center per year for three years). The NIAMS, NINDS, and NICHD signed a Memorandum of Understanding (MOU) with the MDA in May 2003 to formalize this partnership. The principal investigators of each center have been invited by MDA to apply for these supplemental funds, and MDA expects to make awards in early January 2004.

NIAMS will continue to work collaboratively with NINDS and NICHD on the Centers program. As required in the "Muscular Dystrophy Cooperative Research Centers" solicitation, a steering committee to ensure overall coordination of the program is being formed, and will include the scientific program officers from NIAMS, NINDS, and NICHD. However, the Centers program is only one of the many ways that NIH is working to further MD research and training. All three institutes are represented on the Muscular Dystrophy Coordinating Committee (MDCC), which held its first meeting in July 2003, and the group is currently in the process of developing a research and education plan for MD. In recent years, the three institutes have worked together to co-sponsor initiatives and workshops on MD. All three institutes also participate in the MD Research Task Force to help guide efforts to intensify research and training related to muscular dystrophy. It is important that NIH use its resources to support a wide range of activities on MD, including support for the new centers program. Such a multi-faceted approach will likely yield the most significant advances in understanding and treating the muscular dystrophies.

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Scleroderma - The Committee encourages NIAMS to collaborate with other Institutes, including NHLBI, NIDDK, and NIDCR, to generate additional research opportunities for scleroderma to identify genetic risk factors and safe and effective treatments. (p. 80)

Action taken or to be taken

Scleroderma is an autoimmune disease - a broad category of diseases in which the body's immune system attacks the body's own tissues as if they were foreign invaders - causing significant damage to target 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.

The field of autoimmunity is currently exploding with activity and newly launched initiatives. Many NIH Institutes, including NIAMS, NHLBI, NIDDK, and NIDCR are active members of the NIH Autoimmune Diseases Coordinating Committee (ADCC), which is led by the National Institute of Allergy and Infectious Diseases. The ADCC provides a forum for coordinating research efforts for autoimmune diseases and brings together various stakeholders including the NIH, CDC, FDA, HRSA, AHRQ, and other public and private organizations. The Committee recently developed a comprehensive research plan for autoimmune diseases, including scleroderma.

The plan is based on the premise that information learned from studying one autoimmune disease will provide valuable information for all autoimmune diseases. The plan highlights research opportunities likely to have the greatest impact on accelerating discovery of treatments or cures. Research opportunities highlighted include identifying the genetic and environmental risk factors for developing autoimmune diseases, and developing a centralized clinical research network to conduct multi-institutional clinical trials.

Approximately 80 percent of scleroderma patients will eventually develop some degree of lung involvement, which causes significant morbidity and mortality in scleroderma patients. In collaboration with the NIAMS, the NHLBI is supporting a multi-center clinical trial to evaluate the efficacy of oral cyclophosphamide in stabilizing or improving lung function in scleroderma patients who have active lung inflammation (alveolitis). Thirteen medical centers in the United States began enrolling patients in September 2000 and will complete enrollment within the next few months. The Steering Committee for this study is planning a second treatment trial that would evaluate other immunosuppressive drugs for improving the secondary pulmonary hypertension that causes scleroderma patients to develop heart failure. The NHLBI also supports investigator-initiated research on the molecular mechanisms that contribute to the development of pulmonary fibrosis in scleroderma patients, and funds numerous projects that address various aspects of pulmonary hypertension, myocardial and pulmonary fibrosis, and cardiac arrhythmias. A new NIAMS funded project is using a unique sample set - lung tissue from scleroderma patients undergoing lung transplant surgery, as well as lung tissue from unused donor lungs - to facilitate investigation into the cellular changes that cause the hardening of the lungs. Another new NIAMS-funded study is uncovering the cellular activities inside the blood vessels in scleroderma patients. In collaboration with the Office of Research on Women's Health, NIAMS funds research aimed at uncovering the cellular and molecular processes that contribute to the development of scleroderma.

The NIDDK participates in efforts to enhance progress in scleroderma by conducting basic research on the biology of the gastrointestinal tract, as well as translational research on gastroesophageal reflux disease (GERD), one of the most common gastrointestinal manifestations of scleroderma. Similar NIDDK-supported fundamental and clinical research on renal disease may provide the foundation for developing better treatments for kidney involvement in scleroderma. Furthermore, the NIDCR would welcome receipt of high-quality applications relevant to the dental and craniofacial complications associated with scleroderma.

The NIAMS supports several projects which focus on new and innovative treatment options for patients with scleroderma including: a multicenter trial to test type 1 collagen as a treatment for localized forms of scleroderma; ultraviolet phototherapy; and stem cell transplantation. In addition, behavioral scientists supported by the Institute have found that managing pain and depression may lead to improved functioning and quality of life for patients with scleroderma.

The NIAMS has taken a leadership role in generating research opportunities for scleroderma by supporting a national Scleroderma Family Registry and DNA Repository. The overall objective of this registry is to identify genes that influence susceptibility to the disease. The repository collects and stores genetic material (DNA) and blood serum from scleroderma patients and their families and serves as a national resource to scientists studying the genes associated with scleroderma. The NIAMS facilitates the transfer of basic research findings into clinical practice by supporting large-scale centers of research. For example, NIAMS supports two specialized centers of research (SCORs) in scleroderma - one at the University of Texas Health Science Center and one at the University of Tennessee. These SCORs focus only on scleroderma, and they serve as a national resource for researchers studying scleroderma. The NIAMS also supports a new multidisciplinary clinical research center with a special focus on lupus and scleroderma in African Americans. In the area of childhood rheumatic diseases, the NIAMS supports a multidisciplinary clinical research center focused on juvenile scleroderma and other pediatric rheumatic diseases.

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Vitiligo treatments for children - The Committee urges NIAMS to enhance research efforts through all available mechanisms, as appropriate, to identify the causes of this disease and develop pediatric treatment options for vitiligo. (p. 80)

Action taken or to be taken

Vitiligo is a pigmentation disorder in which melanocytes (the cells that make pigment) in the skin, the mucous membranes, and retina (inner layer of the eyeball) are destroyed. As a result, white patches of skin appear on different parts of the body. The hair that grows in areas affected by vitiligo usually turns white. In the United States, 2 to 5 million people have the disorder. Ninety-five percent of people who have vitiligo develop it before their 40th birthday.

The NIAMS supports a variety of projects examining the cause of vitiligo including genetic studies of vitiligo or other hereditary diseases of pigmentation, with the aim of discovering the genes that cause or predispose individuals to develop the disease. The Institute also supports a number of grants investigating the normal process of melanin (pigment that determines skin color) production and delivery from the melanocyte to the keratinocyte (primary cell of the skin). Research indicates that vitiligo appears to be more common in people with other autoimmune disorders (conditions in which a person's immune system reacts against the body's own organs or tissues). The NIAMS supports an extensive portfolio addressing autoimmune disorders and advances in this area will benefit the development of treatment and prevention strategies for autoimmune-related skin diseases, such as vitiligo, for both children and adults.

While vitiligo affects all races and both sexes equally, the psychological and social consequences are particularly profound in people of color who have the disease. Not only is the individual affected, but burden of disease can extend to the family, the workplace, and society as a whole. To this end, in September 2002, NIAMS sponsored the "Workshop on the Burden of Skin Disease." A diverse group of investigators and patients discussed the elements that comprise the burden of skin diseases and their impact on public health and daily living; current knowledge and data-collection instruments, and how to access the data more effectively; and future data needs and instruments for facilitating the collection of the data. In response to this workshop, a solicitation designed to encourage research in the area of burden of skin disease is currently under development and is set for release in early 2004.

Additionally, the NIAMS sponsored a workshop in September 2003 on immune modulation in the treatment of skin diseases. The workshop examined immune regulation as it relates to various skin diseases and their therapies. Recommendations from this meeting will facilitate the development of future research initiatives focused on treatment strategies for a range of skin diseases, including vitiligo.

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Marfan syndrome - The Committee commends NIAMS for its vital support of research on heritable disorders of connective tissue (HDCT), which includes Marfan syndrome. Marfan syndrome is a life-threatening, progressive and degenerative genetic disorder affecting several organ systems. The Committee encourages NIAMS to collaborate with other Institutes and patient foundations to develop a comprehensive analysis of research opportunities including a multi-institute research plan for Marfan syndrome and related disorders through all available mechanisms, as appropriate. (p. 80)

Action taken or to be taken

Marfan syndrome is a heritable condition that affects the connective tissue. Marfan syndrome is caused by a defect (mutation) in the gene that determines the structure of fibrillin, a protein that is an important part of connective tissue. Because connective tissue is found throughout the body, Marfan syndrome can affect many body systems, including the skeleton, eyes, heart and blood vessels, nervous system, skin, and lungs. It is estimated that at least 1 in 5,000 people in the United States have the disorder.

In November 2000, the NIAMS joined the NIH Office of Rare Diseases, the National Institute of Child Health and Human Development (NICHD) and several nonprofit organizations outside NIH, in sponsoring the Third Workshop on Heritable Disorders of Connective Tissue. This Workshop focused on multidisciplinary approaches to the question of pathogenesis of connective tissue diseases, such as Marfan syndrome, osteogenesis imperfecta, and Ehlers-Danlos. All levels of investigation (genetic approaches, biochemical approaches, developmental approaches, and cell-matrix interactions) were discussed. By focusing on multidisciplinary approaches and common themes important in matrix biology, the goal was to stimulate new collaborations between researchers interested in different diseases and facilitate more rapid progress in this area. As a result of this Workshop, NIAMS and the National Heart, Lung, and Blood Institute (NHLBI) released a request for applications focused on research on heritable disorders of connective tissue. The NIAMS funded eight new grants in response to this solicitation and the NHLBI awarded several grants as well. These projects have complemented other NIH-sponsored research being conducted around the country which is examining areas of research such as the development of mouse models that carry mutations in the fibrillin gene and the evaluation of treatment options for individuals with Marfan syndrome.

In addition to these collaborations, the NIAMS continues to work closely with other NIH components such as the National Institute on Aging and the NICHD in exploring research in other heritable disorders of connective tissue such as osteogenesis imperfecta. In 2001, the NIAMS announced the award of four new projects, which will add information to the body of knowledge for other heritable disorders of connective tissue.

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Pemphigus registry - The Committee encourages NIAMS to consider establishing a national pemphigus registry, which would be important to the scientific community and patients in identifying the epidemiology, improving the understanding of the potential causes, and assessing the value of therapies for this chronic and life-threatening autoimmune disease. (p. 80)

Action taken or to be taken

Pemphigus is an umbrella term for a group of rare, autoimmune blistering diseases of the skin and mucous membranes. Normally, our immune system produces antibodies that attack viruses and bacteria in an effort to keep us healthy. In a person with pemphigus, however, the immune system mistakenly perceives the cells in skin and mucous membranes as foreign, and attacks them. The part of the cells that are attacked in pemphigus are proteins called desmogleins. These proteins form the glue that attaches adjacent skin cells, keeping the skin intact. When desmogleins are attacked, the cells become separated from each other. This causes burn-like lesions or blisters that do not heal. In some cases, these blisters can cover a significant area of the skin.

The NIAMS supports a broad range of research on pemphigus, to better understand what causes the various forms of this disease and to help develop more effective therapies. This includes projects using mouse models to explore the biological function of desmogleins in cell adhesion in the skin, and efforts to elucidate the environmental and genetic risk factors associated with pemphigus in certain populations. Other scientists are working to clarify the causes of blister formation in both mouse models and human patients with pemphigus and bullous impetigo, a common skin disease. A better grasp of the mechanisms of blister formation could shed light on new treatment strategies. The Institute also supports the training of investigators engaged in patient-oriented research on autoimmune skin diseases such as pemphigus. This includes funding for scientists who are studying therapeutic interventions to minimize steroid-induced osteoporosis in patients with the disease. Although the Institute does not currently support a research registry for pemphigus, we would welcome meritorious applications to develop such a resource the next time the NIAMS announces an open competition to establish new research registries.

In addition, the NIAMS recently held two meetings that have important implications for those affected by pemphigus, as well as for scientists studying the disease. In September 2002, the Institute sponsored a meeting entitled, "Workshop on the Burden of Skin Disease." The purpose of this meeting was to examine the current definition of burden of skin disease and to evaluate the existing tools used to measure disease burden. In follow-up to this meeting, the NIAMS is developing an initiative to identify and prioritize data sets and data collection instruments that may be useful in answering burden of skin disease research questions. This effort will also point to missing data and instruments that may need to be developed in the future. In September 2003, the NIAMS, in conjunction with the NIH Office of Rare Diseases, held a conference on immunomodulatory drugs in the treatment of skin diseases. The conference explored what we can learn about the pathophysiology of skin diseases by looking at how new, immunomodulatory drugs work. Pemphigus was one of the diseases discussed at this meeting. We anticipate that the recommendations from this conference will help identify scientific opportunities that may promote a better understanding of various skin diseases such as pemphigus and how best to treat them. Finally, the NIAMS is committed to developing and disseminating science-based health information for patients and providers who are affected by autoimmune diseases such as pemphigus. To this end, the Institute has developed an information packet on pemphigus and other blistering disorders of the skin, and a "Questions and Answers" booklet on autoimmunity.

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Burden of skin diseases - The Committee encourages NIAMS to consider supporting the development of new tools to measure the burden of skin diseases and training researchers in this area. (p. 80)

Action taken or to be taken

In September 2002, the NIAMS sponsored a meeting entitled, "Workshop on the Burden of Skin Disease." The purpose of this meeting was to examine the current definition of burden of skin disease and to evaluate the existing tools used to measure burden. In follow up to the recommendations of the September 2002 meeting and on recommendation of the planning committee, NIAMS proposes to survey the existing data sets that could be mined to determine components of the burden of skin disease; survey available data collection instruments to collect such data as they relate to disease in general skin disease as a whole, and specific skin diseases; and array the available data in a matrix against personal, family and societal impact. The NIAMS is currently developing a request for proposals which will provide support for a contract to address these recommendations. Award of this contact is set for FY 2004. This contract will identify and prioritize missing data and data collection instruments to allow efficient development of the missing instruments and data in subsequent projects/initiatives.

In September 1999, the NIAMS co-sponsored a meeting entitled, "Epidemiology/Health Services Research: Prospects for Developments in Skin Disease." Recommendations from this meeting were used to develop a request for applications which focused on bringing new researchers into the field of epidemiology, clinical trials research, and outcomes research in skin diseases. Through a public-private collaboration, several projects have been awarded in response to this solicitation. These projects are examining areas such as patient-oriented outcomes research, the identification of high risk populations, and surrogate marker identification.

FY 2004 Senate Appropriations Committee Report Language (S. Rpt. 108-10)

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Bone and Cartilage Diseases - The Committee urges NIAMS to explore new avenues for cell- and gene-based therapies for the treatment of bone and cartilage diseases, such as osteoporosis, Paget's disease, and osteogenesis imperfecta. Identifying new targets for enhancing bone formation and blocking bone destruction should be a major focus, with studies that integrate basic and clinical approaches regarding bone forming cell development. (p. 140)

Action taken or to be taken

Please refer to page NIAMS-30 of this document for NIAMS' response to this significant item regarding Bone Diseases.

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Lupus - The Committee encourages the Institute to provide the highest possible funding level for lupus research and explore all possible scientific opportunities for prevention, treatment and cure of this devastating disease. (p. 141)

Action taken or to be taken

Please refer to page NIAMS-28 of this document for NIAMS' response of this significant item regarding Lupus.

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Neurofibromatosis - Neurofibromatosis [NF] is a common genetic disorder of the nervous system. Its symptoms vary in kind and degree and may be severely disabling, mildly disfiguring, or can even go undetected. Some individuals with NF have many skin neurofibromas (tumors on the nerves) on the face and body and light brown (café-au-lait) spots on the skin. A variety of skeletal abnormalities may also be present such as bowing of the legs, curvature of the spine (scoliosis), or thinning of the shin bone. The Committee requests that NIAMS work in partnership with the NF community to identify and explore research of mutual concern and to be prepared to discuss its progress at the fiscal year 2005 appropriations hearing.(p. 141)

Action taken or to be taken

The neurofibromatoses are genetic disorders of the nervous system that primarily affect the development and growth of neural (nerve) cell tissues. These disorders cause tumors to grow on nerves and produce other abnormalities such as skin changes and bone deformities. The neurofibromatoses occur in both sexes and in all races and ethnic groups. Neurofibromatosis type 1 (NF1) is the more common type of the neurofibromatoses, occurring in about 1 in 4,000 individuals in the United States. At the NIH, the National Institute of Neurological Disorders and Stroke (NINDS) is the lead component for research on the neurofibromatoses.

The NIAMS has a long and successful history of partnering with public and private organizations for the advancement of science. To this end, NIAMS welcomes the opportunity to work with other NIH components and private organizations to advance research in the area of neurofibromatosis, particularly when addressing the skin and bone manifestations associated with this disorder. Additionally, many of the outstanding projects currently funded in the areas of skin and bone research will contribute to the body of knowledge for neurofibromatosis. For example, current projects in skin pigmentation, skeletal development and bone growth, correction of skeletal deformities, nonunions (failure of a fractured bone to heal normally), and scoliosis (curvature of the spine) and other spinal deformities may have important implications for neurofibromatosis research.

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Pemphigus Registry - The Committee urges NIAMS to establish a National Pemphigus Registry to identify the epidemiology, improve the understanding of the potential causes, and assess the value of old and new therapies for the chronic, life-threatening autoimmune disease known as pemphigus.

Action taken or to be taken

Please refer to page NIAMS-36 of this document for NIAMS' response to this significant item regarding the Pemphigus Registry.

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Scleroderma - The Committee is encouraged by NIAMS's growing interest in scleroderma, a chronic and progressive disease that predominantly strikes women. Scleroderma is a disfiguring and can be life-threatening and effective treatments are lacking. More research is critically needed in order to identify the genetic risk factors for scleroderma and to develop safe and effective treatments. The Committee urges NIAMS to collaborate with other Institutes, including NHLBI, NIDDK, and NIDCR, to generate additional research opportunities for scleroderma. (p. 141)

Action taken or to be taken

Please refer to page NIAMS-32 of this document for NIAMS' response to this significant item regarding Scleroderma.

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Skin Disease - The Committee was pleased to learn that NIAMS conducted a workshop on the "Burden of Skin Diseases." The Committee encourages NIAMS to examine the findings from the workshop and encourages the development of new tools to better measure the burden of skin diseases, and the training of researchers in this important area. The Committee further encourages NIAMS to move forward expeditiously to generate the required data in collaboration with the Center for Disease Control and Prevention [CDC], Agency for Health Care Policy and Research [AHCPR], and Health Resources and Service Administration [HRSA], as well as other agencies and organizations that participated in the conference. (p. 141)

Action taken or to be taken

Please refer to pages NIAMS-37 of this document for NIAMS' response to this significant item regarding Skin Disease.


FY 2004 Conference Committee Report Language (H. Rpt.108-401)

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Duchenne muscular dystrophy - The conferees urge NIAMS, in collaboration with NINDS and NICHD, to accelerate clinical trials to improve treatment for patients with Duchenne muscular dystrophy. The conferees encourage NIAMS to actively seek and assess clinical trial proposals and to expedite the review process for clinical research in Duchenne muscular dystrophy. The conferees encourage the funding for three additional centers of excellence by the end of fiscal year 2004. (p. 773)

Action taken or to be taken

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), along with the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Child Health and Human Development (NICHD), are committed to improving the treatment of patients with muscular dystrophy (MD). Clinical research is an important component of the recently established Muscular Dystrophy Cooperative Research Centers (MDCRCs). These centers - which are being funded by NIAMS, NINDS and NICHD - support an integrated basic and clinical research program focused on improving knowledge and treatment of MD. The centers are designed to accelerate the translation of fundamental scientific advances to the clinic through close interactions between basic researchers and clinicians. Two of the centers, at the University of Pittsburgh and the University of Washington, have a particular focus on the Duchenne form of MD.

The NIH has taken other proactive steps to advance clinical and translational research on muscular dystrophy. In January 2001, NIAMS and NINDS issued a program announcement with set-aside funds entitled "Therapeutic and Pathogenic Approaches for the Muscular Dystrophies." This solicitation has resulted in a number of funded projects designed to advance treatment interventions for MD. One study, a clinical trial funded by NINDS, is testing whether the common antibiotic gentamicin has therapeutic potential for patients with both the Duchenne and limb-girdle forms of MD. This trial may provide new insights that will help shape the course of future clinical studies in this area. Other projects funded as a result of this initiative focus on bridging the gap between basic research and clinical trials. This translational research is needed to determine the most promising clinical strategies to bring to trial. For example, studies funded by NIAMS and NINDS are aimed at improving gene therapy for Duchenne MD, including gene vector design and vector delivery methods. Other work supported by NIAMS is focused on special muscle-generating stem cells that can improve muscle regeneration and deliver the missing protein dystrophin to damaged muscles in a mouse model of DMD. Such studies of muscle cell transplantation in animal models could provide insights for developing new treatments for human patients. The NIH continues to welcome new proposals for translational and clinical research aimed at treating and delaying the progression of MD and related neuromuscular diseases.

The NIH will continue its efforts to further basic, translational, and clinical research in MD in the coming years. During fiscal year (FY) 2004, the NIH plans to re-issue the solicitation for the MDCRCs, and expects to fund up to two additional centers - one each by NIAMS and NINDS - in FY 2005. It is important to note that the MDCRC program is only one of the many ways that NIAMS, NINDS and NICHD are working together to further MD research. In recent years, the three institutes have co-sponsored initiatives and workshops on MD. All three institutes are represented on the Muscular Dystrophy Coordinating Committee (MDCC), which held its first meeting in July 2003. The MDCC is currently in the process of developing a research and education plan for MD. It is critical that NIH use its resources to continue to support a wide range of activities on MD. Such a multi-faceted approach will likely yield the most significant advances in understanding and treating the muscular dystrophies.