Significant Items in House, Senate, and Conference Appropriations Committee Reports
FY 2006 Budget

February 2005 (historical)

FY 2005 House Appropriations Committee Report Language (H. Rpt. 108-636)

Item

Bone diseases - The Committee encourages NIAMS to support trans-NIH research into all aspects of genetics and gene therapies for the treatment of metabolic bone diseases, the role of environmental and lifestyle factors in bone disease, the effects of depression and cardiovascular disease on bone disease, the impact of mechanical loading of bone, and on bone health and osteoporosis in special groups, such as non-Caucasian ethnic groups. (p. 91)

Action taken or to be taken

The NIAMS leads the Federal research effort in bone diseases, and supports science ranging from very basic studies to clinical and translational projects, as well as early intervention and prevention efforts. The Institute actively collaborates with a variety of Federal and private organizations to advance the field of bone disease research. For example, the NIAMS leads the Federal Working Group on Bone Diseases, an interagency committee that offers a forum for sharing information and facilitating the development of collaborative bone research activities based on each agency's mission. Several other NIH components including the National Institute on Aging, the National Institute of Diabetes, Digestive, and Kidney Disorders, the National Institute of Dental and Craniofacial Research, the National Center for Complementary and Alternative Medicine, and the National Cancer Institute participate in working group activities. Other Federal agencies such as the Agency on Healthcare Research and Quality, Centers for Disease Control and Prevention, Food and Drug Administration, Department of Veterans Affairs, and the Department of Education are also active participants.

In the area of gene- and cell-based research, NIAMS-supported researchers have recently used a combination of mouse breeding and genetic technology to identify a gene that strongly influences peak bone mass in mice. The gene, which is present in humans as well as mice, was not previously known to be involved in bone biology, and hence represents a promising new target for development of drugs that could prevent or reverse the bone loss that leads to osteoporosis.

Research is currently underway to investigate the potential connection between bone health and cardiovascular disease. An ongoing collaboration between NIAMS and NHLBI has yielded significant insights into the parallels between bone formation and the vascular calcification that is a hallmark of cardiovascular disease. In addition, studies of bone mass are revealing the close connection between bone biology and fat metabolism, long-recognized as a major factor in cardiovascular disease.

The NIAMS supports a broad range of investigations into the response of bone to mechanical loading. These projects include studies of the cellular and molecular mechanisms by which load is detected and translated into new bone growth, as well as efforts to develop therapies that will take advantage of these mechanisms to increase bone mass. Other NIAMS-supported research has shown that specific strength training and resistance exercises can retard and even reverse bone loss in healthy postmenopausal women, and that estrogen replacement is not necessary to gain the benefit of the exercise.

In collaboration with the National Institute on Aging, the NIAMS supports a large study of osteoporosis and other age-related diseases in men, called Mr. OS. This project complements an ongoing study of osteoporotic fractures in women that has been supported by the Institute for over a decade. The Mr. OS effort will facilitate gender comparisons and address the issue of why osteoporotic fractures are more common in women.

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Scoliosis - The Committee encourages NIAMS, in coordination with other institutes, to enhance research relevant to scoliosis to identify bio-mechanical causes and to develop genetic strategies to prevent the condition. (p. 91)

Action taken or to be taken

The NIAMS, along with the National Eye Institute and the National Institute on Child Health and Human Development, supports a broad range of research to better understand skeletal development, mechanical properties, and spinal injury and disorders. These diverse scientific studies complement research that is looking directly at scoliosis and how best to diagnose and treat the disease.

The Institute is actively supporting genetics research in the area of scoliosis. For example, the NIAMS supports gene expression studies of early spinal development that aim to identify new genes associated with the development of scoliosis at birth. Other researchers are searching for the genes responsible for familial scoliosis, a complex genetic disorder with limited treatment options.

Exciting work is also being done to better understand the factors that affect skeletal stability and instability in both humans and animals. Using a novel animal model, researchers are looking at how structural stability increases in the developing mammalian backbone. The results of this study should shed light on the causal factors associated with back instability, as well as identify structures that protect the spinal cord from damage. NIAMS also supports the development of new technologies with the potential to improve treatment of skeletal disorders and facilitate repair following trauma to the skeleton.

NIAMS-supported researchers are examining methods for improving spinal visualization, including the development of three-dimensional imaging technologies to allow for detailed analyses of the spine in a moving person, without the risks of radiation associated with traditional x-rays. Related research is being done to adapt methods of topographic surface mapping to examine the back's surface and develop mathematical models to track spine curvatures. These and other novel approaches have the potential to increase the safety and effectiveness of tools used in the management and treatment of scoliosis.

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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 disfiguring and can be life-threatening, and effective treatments are lacking. The Committee encourages NIAMS to collaborate with other Institutes, including NHLBI, NIAID, NIDDK, and NIDCR, to generate additional research opportunities for scleroderma to identify genetic risk factors and safe and effective treatments. (p. 91)

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. The NIAMS continues to work closely with other public and private organizations to advance scleroderma research. For example, NIAMS, along with NHLBI, NIDDK, and NIDCR, is an active member of the NIH Autoimmune Diseases Coordinating Committee (ADCC), which is led by the NIAID. The ADCC provides a forum for coordinating research efforts for autoimmune diseases, including scleroderma, and brings together various stakeholders including the NIH, Centers for Disease Control and Prevention, Food and Drug Administration, Health Resources and Services Administration, Agency for Healthcare Research and Quality, and other public and private organizations.

The NIAMS funds two specialized centers of research investigating the genetic and environmental factors that contribute to developing scleroderma. The Institute 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. Additionally, the Institute 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.

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 multicenter 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 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 bone marrow 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. In collaboration with the NIH Office of Research on Women's Health, the NIAMS funds research aimed at uncovering the cellular and molecular processes that contribute to the development of the disease. These studies may help unravel the molecular basis of scleroderma and ultimately provide therapeutic targets.

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Vitiligo treatments for children - Vitiligo is an environmental and genetic auto-immune disease of unknown origin which affects about three to six million Americans. Almost fifty percent develop the disease in childhood, with the median age of onset at four years of age. In its most severe forms, patients have milky white patches covering widespread areas of the body due to the loss of pigment in these areas. Especially for young children, the physical pain caused by severe burns from the harmful effects of sunlight and the emotional pain caused by people confusing vitiligo with an infectious disease diminishes the quality of a patient's life. There are no FDA-approved 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. 92)

Action taken or to be taken

NIAMS-supported researchers have made significant advances in the field of vitiligo research. The recent discovery of two separate genetic links provides additional insight into the pathology of the disease, as well as in to the development of potential therapeutic options. Additionally, NIAMS supports an extensive portfolio addressing autoimmune disorders (conditions in which a person's immune system reacts against the body's own organs or tissues). 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.

The Institute supports a number of projects examining the causes of vitiligo, including genetic studies of vitiligo and other hereditary diseases of pigmentation, to discover the genes that cause or predispose individuals to develop the disease. For example, NIAMS-supported researchers are gathering information from patient populations in the United States and the United Kingdom to identify genetic susceptibility for this disease. This project has recently been expanded to include minority populations, where the genetics may be different. The long-term significance of this work is the development of specific therapeutic approaches and prevention strategies.

It is important to understand not only the genetic basis but also the triggers from the environment that may lead to the development of vitiligo and other autoimmune diseases in order to make progress in prevention and treatment. To this end, 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 collaboration with other institutes to support research on Marfan syndrome, a life-threatening, progressive and degenerative genetic disorder. Marfan syndrome is characterized by cardiovascular, skeletal and ocular manifestations and its cardiovascular complications can result in premature death. Insights gained from research in this area may have implications for the understanding of other connective tissue disorders, other genetically mediated diseases, and the larger population of aging adults with thoracic aneurysms from a variety of causes. The Committee encourages NIAMS to focus on research opportunities which have the potential to advance non-surgical treatment options, through all appropriate mechanisms. (p. 92)

Action taken or to be taken

Marfan syndrome is a common inherited disorder caused by a mutation in the fibrillin gene. This mutation causes the tendons, ligaments, and other connective tissues in the body to weaken. Marfan syndrome can affect the heart, skeletal system, eyes, and other organs in the body and symptoms range from mild to severe. The most serious symptoms involve the aorta, the large artery that carries blood from the heart to the rest of the body. Marfan syndrome weakens the connective tissue in the walls of the aorta, thereby increasing the chances that the artery will bulge, tear, or rupture B which can be life-threatening.

The NIAMS recently awarded a program project grant to develop a multi-site translational research program in Marfan syndrome. The long-term goal of this program is to translate basic research in matrix biology into treatment strategies for individuals with Marfan syndrome and related disorders of connective tissue. The program will utilize a comprehensive and multidisciplinary approach that integrates the scientific interest and expertise of four leading laboratories in this and related research fields. Researchers will study genetically engineered mouse models of Marfan syndrome to uncover the abnormal cellular activities that contribute to this disorder and will translate this new knowledge into more effective therapies.

The NIAMS also works closely with other NIH components in exploring research in other heritable disorders of connective tissue. It will continue its efforts to support basic, translational, and clinical research in Marfan syndrome and other heritable disorders of connective tissue in the future.

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Atopic dermatitis - Atopic dermatitis (AD) is one of the most common skin disorders experienced by infants and children. Over 90 percent of cases are diagnosed before the age of five. Patients with AD suffer with chronic skin inflammation and itching that disrupt sleep and reduce quality of life. An estimated 17 percent of children in the United States have atopic dermatitis, a dramatic increase above pre-1960s levels. The reason for this increase is unknown, but mirrors the increased rates of asthma and requires greater study. Of additional concern, individuals who have active or dormant AD are at high risk for serious adverse reaction to the smallpox vaccine. The Committee encourages NIAMS to work with NIAID to spearhead an initiative to encourage investigator-initiated research on AD as it relates to smallpox vaccination as well as the progression to asthma and other allergic diseases. (p. 92)

Action taken or to be taken

The NIAMS and other components of the NIH support research that is looking directly at the causes of, and treatments for, atopic dermatitis (eczema), a chronic inflammatory skin disease. For example, researchers from NIAMS are investigating Langerhans cells (cells that help protect the body from infection) to determine their role in atopic dermatitis. Other NIAMS-supported researchers are investigating the role of bacteria in triggering atopic dermatitis.

Developing new treatments for atopic dermatitis is an exciting area of research. NIAMS-funded researchers are using a mouse model of atopic dermatitis to gain insights into the cause of this disease and to evaluate the effectiveness of new treatment options. NIAMS supports research comparing the effectiveness of topical (applied directly to the skin) treatment options versus intravenous methods to treat the inflammation associated with atopic dermatitis.

The NIAMS currently supports research on atopic dermatitis related to susceptibility to eczema vaccinatum (EV), the most common life-threatening complication of the smallpox vaccination. EV occurs almost exclusively in people with a history of atopic dermatitis. The NIAMS would welcome opportunities to collaborate with NIAID to encourage investigator-initiated research on atopic dermatitis as it relates to EV and the smallpox vaccination.

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Burden of skin diseases - The Committee commends NIAMS for conducting a workshop on the burden of skin diseases. The participants in the workshop recommended that skin disease-specific measures be developed in order to generate data on the incidence, prevalence, economic burden and disability attributable to these diseases. The Committee encourages NIAMS to continue to work with the scientific community to implement the recommendations of the workshop participants. (p.93)

Action taken or to be taken

In September 2002, the NIAMS sponsored the "Workshop on the Burden of Skin Disease" to discuss 1) the elements that comprise the burden of skin diseases and their impact on public health and daily living; 2) current knowledge and data-collection instruments; 3) how to access the data more effectively; and 4) future data needs and instruments for facilitating the collection of the data. The lessons learned from this workshop will serve as a paradigm for other areas - all of which share the challenge of defining the burden of a disease on an individual, the family, the workplace, and society as a whole.

The NIAMS has recently awarded a contract which will address the recommendations of the workshop participants. Researchers will determine whether or not existing skin disease databases can be used to address disease burden. During this process, gaps in data will be identified. If it is determined that existing databases cannot address the burden of skin disease appropriately, or the existing gaps cannot be addressed, recommendations will be made for the development of new instruments and database designs that could effectively address the burden of skin disease.

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Psoriasis - Psoriasis is a chronic, immune-mediated disease that affects more than five million Americans. A 1999 NIMH-supported study found that patients with psoriasis reported reduction in physical and mental functioning comparable to that seen in cancer, arthritis, hypertension, heart disease, diabetes, and depression. The Committee considers research on psoriasis and psoriatic arthritis important, and is pleased that NIAMS helped create a psoriasis tissue bank from which the first several psoriasis genes have been identified. The Committee encourages NIAMS to support additional research into the identification of other genes expected to play a role in psoriasis pathogenesis and to strengthen clinical research on potential therapies for psoriasis and psoriatic arthritis. (p. 93)

Action taken or to be taken

Psoriasis is a common and chronic skin disease characterized by scaling and inflammation. It affects millions of Americans, including people of all ages. The NIAMS actively supports psoriasis research to improve our understanding of the disease, develop more effective treatments, and expand our knowledge of genes that play a role in the development of this disease.

A team of NIAMS-supported researchers has recently identified two genes associated with psoriasis. The region between these two genes acts as a binding site for a protein that normally serves to regulate genes involved in immune reactions. The researchers found that when this region is altered, susceptibility to psoriasis occurs. These findings provide further progress toward understanding the cause of psoriasis in patients with a family history of the disease. This information will be used in future studies to investigate other psoriasis populations, as well as to examine other inflammatory diseases.

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 development of skin diseases, including psoriasis, by looking at how new immunomodulatory drugs work. We anticipate that the insights from this meeting will help identify scientific opportunities that may promote a better understanding of various skin diseases and how best to treat them.

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Mucopolysaccharidosis (MPS) - The Committee is aware of NIAMS's recent efforts with NIDDK to facilitate communication between MPS and Lysosomal Storage Disorder investigators with bone pathology and connective tissue scientists to examine problematic issues in this area of study. The Committee encourages NIAMS to enhance its efforts to directly support and collaborate with NIDDK on bone and joint diseases in MPS disorders. (p. 93)

Action taken or to be taken

The mucopolysaccharidoses consist of a group of inherited metabolic disorders caused by a deficiency of the specific lysosomal enzymes needed to break down mucopolysaccharides. Mucopolysaccharides are long chains of sugar molecules used to build connective tissues and organs in the body. When mutations occur in the genes for the enzymes involved in the normal turnover of mucopolysaccharides, excess amounts of them are stored in the body. The buildup of these sugar molecules inside cells causes various problems, including bone and joint irregularities. Progressive physical disability results from bone and joint manifestations associated with the mucuopolysaccharidosis.

The NIAMS supports a broad portfolio of basic, clinical, and translational research in bone and connective tissue biology. Broad areas of interest include skeletal development, metabolism, functional aspects of cartilage, components of connective tissues, and etiology and pathogenic mechanisms in heritable disorders of connective tissue. The Institute also supports the development of new technologies with the potential to improve treatment of skeletal disorders and facilitate the repair of trauma in the normal skeleton. These include drugs and nutritional interventions, joint replacement, bone and cartilage transplantation, and gene therapy. Advances in these fields may provide researchers examining mucopolysaccharidosis with additional information related to basic biology that may lead to the development of potential therapeutic options. Further, the NIAMS encourages highly meritorious applications in mucopolysaccharidosis research relevant to our mission, in an effort to broaden the base of inquiry in fundamental biomedical research.

FY 2005 Senate Appropriations Committee Report Language (S. Rpt. 108-345)

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Arthritis - Arthritis is the leading cause of disability in the United States, with 70 million Americans living with some form of the disease of chronic joint symptoms. The NIAMS is a leader in the field of arthritis research. The committee urges NIAMS to collaborate with other NIH institutes toward a cure for arthritis and related diseases. (p. 138)

Action taken or to be taken

The NIAMS, in collaboration with other NIH institutes, has taken proactive steps to advance the basic, clinical, and translational components of arthritis research. For example, NIAMS, along with other components of the NIH, is supporting research into the application of genetic factors for susceptibility and severity of arthritis. This research has the potential to identify patients most at risk of developing a particular type of arthritis so that appropriate treatment strategies can be applied before the disease progresses. Further, NIAMS funds research using mouse models to uncover the cellular and molecular processes that lead to inflammation, a common characteristic of most types of arthritis.

Quality-of-life research is an active area of interest at the NIH. To address this issue as it relates to arthritis, the NIAMS recently hosted a workshop on the role of fatigue in rheumatic disease. This workshop brought expert scientists and clinicians together to identify knowledge gaps associated with the study and treatment of fatigue in rheumatic disease, including rheumatoid arthritis and osteoarthritis, and to identify how advances in other diseases could be applied to better understand and treat fatigue. In addition to this workshop, the NIAMS, along with other components of the NIH, is involved in an initiative to develop automated instrumentation and procedures to record in a reliable way patient-reported outcomes such as pain or fatigue, which are so important in terms of quality-of-life. Other NIH-supported researchers are studying the effects of cognitive-behavioral therapy, Tai Chi (a form of movement-based meditation), and education on disease severity and mood disturbance.

Osteoarthritis (OA) is the most common form of arthritis, and it not only affects millions of Americans today, but it is also expected to affect many more people in the future as the number of elderly in our country increases. The NIAMS supports a diverse portfolio to improve our understanding of the underlying causes of osteoarthritis, improve the diagnosis and treatment of osteoarthritis, and improve the quality of life for affected individuals. For example, in collaboration with the National Institute on Aging and other NIH components, and pharmaceutical companies, NIAMS launched the Osteoarthritis Initiative, a public-private partnership that brings together new resources and commitment to help identify biomarkers of disease for OA B biological clues to increased susceptibility, early stages of disease, the course of disease, and the response of people with osteoarthritis to various therapies. This initiative should help speed drug development for OA, which is hindered by the lack of objective and measurable standards for disease progression needed for drug evaluation. Patient recruitment began in the spring of 2004. In addition to participating in the Osteoarthritis Initiative, the NIAMS has recently established the Osteoarthritis Biomarkers Network to hasten the pace of discovery of molecular biomarkers for osteoarthritis. Researchers in the United States and Sweden will share clinical, biological, and human resources. Through the network, investigators will learn more about joint destruction by identifying and monitoring biomarkers in joint, bone, and synovial tissues. This could provide the clues needed to define the stages of disease on a more consistent and reliable basis.

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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 perfecta. 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. 138)

Action taken or to be taken

NIAMS-supported researchers are actively exploring the potential use of cell- and gene-based therapies for the treatment of bone and cartilage diseases. For example, researchers have recently used a combination of mouse breeding and genetic technology to identify a gene that strongly influences peak bone mass in mice. The gene, which is present in humans as well as mice, was not previously known to be involved in bone biology, and hence represents a promising new target for development of drugs that could prevent or reverse bone loss.

Other NIAMS-supported researchers are focusing on basic and applied stem cell research. For example, researchers are investigating the growth factors and hormones that influence how stem cells develop, which should guide the development of therapies in bone diseases. Another group of researchers is using stem cell therapy for diseases of bone in a mouse model. This project uses a mouse model of osteogenesis imperfecta to evaluate possibilities of regeneration or repair of bone marrow using mouse stem cells. Other NIAMS-supported investigators will follow programmed cell activity -- specifically, the life and death of a cell -- and show how that activity generates a form of stem cells that are a factor in maintaining adult bone mass. Researchers have also created a genetically modified mouse that develops lesions similar to those of Paget's disease. This mouse model may prove to be a valuable model of the disease process. Finally, other NIAMS-supported researchers have demonstrated that a gene transferred into human cells can be targeted to the collagen gene that is defective in most types of osteogenesis imperfecta.

Osteoarthritis is a disease of wear and tear on the joints. Its progression causes severe pain that results from degraded cartilage, broken-down bone (which creates bony spurs), and sometimes thickened and inflamed synovial tissue. To hasten the pace of discovery of molecular biomarkers for osteoarthritis, the NIAMS has established the Osteoarthritis Biomarkers Network, a collaborative research program between researchers in the United States and Sweden. For the first time, researchers who have been individually studying osteoarthritis biomarkers -- molecular indicators of disease presence and progression -- will share clinical, biological, and human resources. Through the network, investigators will learn more about joint destruction by identifying and monitoring biomarkers in joint, bone, and synovial tissues. This could provide the clues needed to define the stages of disease on a more consistent and reliable basis. The Network complements the ongoing work of the Osteoarthritis Initiative, a public-private partnership that brings together new resources and commitment to help identify biomarkers of disease in osteoarthritis.

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Lupus - The committee is aware of the importance of lupus susceptibility genes. Voluntary health organizations have established a collaboration among many individual research teams throughout the country to accelerate the search for these genes. The committee urges the Institute to pursue this collaboration and to provide increased funding so that sufficiently large patient cohorts can be developed that will facilitate research in this area. Because lupus is a disorder that disproportionately affects women of African American, Hispanic and Asian ancestry, appropriate numbers of samples from these populations should be included in these cohorts. The Committee also urges the Institute to consider the importance of creating repositories that might aid research in the genetic aspects of lupus. (p. 138)

Action taken or to be taken

The NIAMS is continuing to enhance its research activities in lupus through a multitude of efforts. For example, the NIAMS supports a large lupus registry and repository designed to accelerate the search for lupus susceptibility genes. This registry collects and updates clinical, demographic, and laboratory data on patients with lupus and their families. Researchers analyze DNA samples to search for the presence of genetic markers. About one-third of the families studied are African American. In addition, researchers are increasing the number of Mexican American and Puerto Rican families affected by lupus who are included in the Lupus Registry and Repository.

Researchers supported by the NIAMS, in collaboration with other components of the NIH - including the National Institute of Allergy and Infectious Diseases, National Center on Minority Health and Health Disparities, and the Office of Research on Women's Health - have 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. 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. Other NIAMS-supported researchers have found two gene forms that appear more frequently in African American female lupus patients. African Americans with lupus have greater morbidity and mortality primarily due to renal (kidney) disease.

To coordinate Federal efforts in lupus research and education, the NIAMS leads the Lupus Federal Working Group. It is comprised of representatives from all relevant HHS agencies and other Federal departments having an interest in lupus. Additionally, the NIAMS leads the new Lupus Biomarkers Working Group, which complements the activities of the Lupus Federal Working Group. In the fall of 2003, the Lupus Biomarkers Working Group invited a group of 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, Food and Drug Administration, and voluntary organizations.

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 cosponsor for this conference, the NIAMS invited leading lupus researchers to discuss the latest scientific discoveries and what they mean for the current and future management of lupus.

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Marfan Syndrome - The Committee commends NIAMS and its collaborative efforts with other institutes to provide vital support for research on Marfan syndrome, a life-threatening, progressive and degenerative genetic disorder. The Committee urges NIAMS to focus on research opportunities that have the potential to advance non-surgical treatment options, through all available mechanisms, as appropriate. (p. 139)

Action taken or to be taken

Please refer to page NIAMS-33 of this document for NIAMS' response to this significant item regarding Marfan syndrome.

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Metabolic Bone Diseases - The Committee encourages NIAMS to support trans-NIH research into all aspects of genetics and gene therapies for the treatment of metabolic bone diseases, the role of environmental and lifestyle factors in bone disease, the effects of depression and cardiovascular disease on bone disease, the impact of mechanical loading of bone, translational research to bring the recent exciting basic discoveries about bone in to clinical practice, and on bone health and osteoporosis in special groups, such as non-Caucasian ethnic groups. (p. 139)

Action taken or to be taken

Please refer to page NIAMS-29 of this document for NIAMS' response to this significant item regarding bone diseases.

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Mucopolysaccharidosis [MPS] - The Committee is aware of recent efforts with NIDDK to facilitate communication between MPS and Lysosomal Storage Disorder investigators with bone pathology and connective tissue scientists to examine problematic issues in this area of study. Research in the underlying pathophysiology of bone and joint lesions, the gene mutations and substrates that are stored and potential therapeutic approaches are of interest to the Committee. The Committee encourages NIAMS to enhance its efforts to directly support and collaborate with NIDDK on bone and joint diseases in MPS disorders. (p. 139)

Action taken or to be taken

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

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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 disfiguring and can be life-threatening and effective treatments are lacking. The Committee encourages NIAMS to collaborate with other institutes, including NHLBI, NIDDK, NIAID, and NIDCR to generate additional research opportunities for scleroderma to identify genetic risk factors and safe and effective treatments. (p. 139)

Action taken or to be taken

Please refer to page NIAMS-31 of this document for NIAMS' response to this significant item regarding scleroderma.

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Tuberous Sclerosis Complex - Tuberous sclerosis complex, or TSC is a genetic disorder that triggers uncontrollable tumor growth in multiple organs of the body, including the skin. The Committee strongly encourages NIAMS to support programs examining the molecular and cellular basis of dermatological lesions in TSC as well as the development of non-surgical treatment for skin manifestations. (p. 139)

Action taken or to be taken

Tuberous sclerosis complex is a rare and genetic, neurological disorder primarily characterized by seizures, mental retardation, and skin and eye lesions. Small benign tumors may grow on the face and eyes, as well as in the brain, kidneys, and other organs. Individuals with tuberous sclerosis complex may experience none or all of the associated symptoms with varying degrees or severity.

The NIAMS supports a broad portfolio of skin disease research that could increase the understanding of the skin manifestations of tuberous sclerosis complex. Fibromas - benign tumors containing fibrous tissues - are commonly seen in patients with the disease. NIAMS-supported researchers are currently studying collagen biochemistry and the function of collagen-producing cells. This research will provide insight on the basic biology of fibroma development. Other NIAMS-supported researchers are examining new topical and laser-based treatments for acne and keloids (skin overgrowths of dense fibrous tissues). This research would provide researchers with a background for developing non-surgical treatment options for patients with tuberous sclerosis complex. Additionally, the NIAMS encourages highly meritorious applications in mission-related research that is directly related to tuberous sclerosis complex, in an effort to broaden the base of inquiry in fundamental biomedical research.