FOR IMMEDIATE RELEASE
July 3, 2006

Arthritis National Research Foundation
Grant Recipients 2006-2007

Science to Treatment: Grant Recipients Aim to Help Patients

Long Beach, CA – The Arthritis National Research Foundation (ANRF) is pleased to announce its 2006-2007 grant recipients. Their critical work will increase our understanding of osteoarthritis, gout, and related autoimmune diseases such as rheumatoid arthritis and lupus. Ultimately, new therapies may be developed from the knowledge gained.

The ANRF Scientific Advisory Board conducts a rigorous peer review of all applications, assuring that recipients of ANRF grants are performing cutting-edge arthritis research under optimal lab conditions at various non-profit research universities and facilities nationwide.

These are Ph.D. and M.D. scientists with several years of research experience; we hope that ANRF’s funding will help them launch their independent research careers.

The following 16 researchers have been funded for the 2006-07 grant award period:

Enzyme Predisposes to Autoimmune Disorders

Nunzio Bottini, M.D., University of Southern California, Los Angeles, CA

Dr. Bottini’s laboratory is studying an enzyme called lymphoid phosphatase, which acts as a critical gatekeeper of the activation of immune cells. Individuals carrying a particular genetic variant of this enzyme are predisposed to a variety of autoimmune diseases, including type 1 diabetes, lupus, and rheumatoid arthritis. In this research project, Dr. Bottini will examine the activity of this enzyme and the genetic variant to help clarify the mechanism of this enzyme in autoimmunity and validate it as a target for new drugs aimed at preventing and treating human autoimmune diseases.

Arthritis and Growth in Children

Hulya Bukulmez, M.D., Case Western Reserve University, Cleveland, OH

Dr. Bukulmez is studying the effect of chronic arthritis on a child’s growth. The most dramatic negative effects are found in children with juvenile rheumatoid arthritis (JRA): destruction of growth plates in children often requires surgical correction. Dr. Bukulmez is studying the mechanisms of inflammation as they relate to growth delay in bones. Her study is at the molecular level with the goal of developing a new treatment for preventing growth delay or correcting the bone and cartilage damage seen during JRA and adult rheumatoid arthritis (RA).

DRAK2: Target for New Therapy

Martina Gatzka, M.D., University of California, Irvine, CA

When T lymphocytes, a type of white blood cell, cannot distinguish between self and non-self tissues, they contribute to inflammation and tissue destruction in autoimmune diseases such as rheumatoid arthritis and lupus. Strategies to specifically block and eliminate self-reactive T lymphocytes are necessary to the development of efficient therapies to treat these immune-mediated diseases.

In healthy individuals, the immune system removes a number of natural surveillance mechanisms to prevent T cells from going awry. One such surveillance mechanism in the body that interferes with T cell activity is called DRAK2 (DAP-related apoptotic kinase-2). Dr. Gatzka is studying DRAK2’s modulation of T cell activation using a mouse model of rheumatoid arthritis. Guided by the results of this research, future work may focus on targeting DRAK2 to develop new therapeutic agents for rheumatic diseases.

Defining Genetics of RA in African Americans

Damini Jawaheer, Ph.D., UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA

This is a genetic study of African Americans with RA. Dr. Jawaheer will test and map the genetic makeup of African Americans with rheumatoid arthritis to determine their susceptibility to the disease and how these genetic markers compare to other ethnic groups which have already been studied. This information will be highly relevant for disease prognosis and treatment and may help lower the burden of arthritis in this ethnic group in the long term.

A Lupus Therapy without Toxicity

Hee Kap Kang, Ph.D., Northwestern University, Chicago, IL

Dr. Kang has developed a therapy to repair a cell defect which may cause lupus. To test this therapy, Dr. Kang’s lab is studying the effects of the injection of a peptide into a lupus-prone mouse.

This peptide therapy appears to be beneficial without any toxic effects so far, and thus might be very important in maintaining tolerance in lupus patients after remission has been induced by more toxic immunosuppressive agents. Apparently healthy subjects and family members of lupus, who might be at risk of developing lupus (as predicted by genetic and biomarkers), might benefit from the peptide therapy because it repairs a defect in regulatory T cell deficiency in lupus.

To recognize his exemplary work, Dr. Kang has been awarded the honor being named the Eng Tan Scholar. Eng Tan, M.D., retired in 2005 from the Scripps Research Institute in La Jolla, CA, was a founding member of the ANRF Scientific Advisory Board and is a world-renowned researcher and clinician in rheumatic diseases and immunology.

Insuring B Cell Tolerance

Julie Lang, Ph.D., University of Colorado Health Sciences Center, Denver, CO

A subset of white blood cells, known as B lymphocytes, is responsible for generating antibodies during an immune response to infection. In normal individuals, the immune system insures that antibodies and immune responses are not directed to self-tissues, a process known as “immune tolerance.” The development of autoantibodies associated with numerous autoimmune diseases, most notably lupus, involves a loss of this B cell tolerance. Dr. Lang’s studies will help elucidate the molecular mechanisms involved in the loss of B cell tolerance leading to autoantibody production, which, in turn, will be important in developing therapies designed to insure B cell tolerance.

Understanding OA

Hee-Jeong Im Sampen, Ph.D., Rush University Medical Center, Chicago, IL

Osteoarthritis is a disease that causes significant pain and disability. Given the increasing prevalence of OA in the aging population around the world, its public health impact and costs will affect all societies in the future. The process of cartilage destruction is progressive, and currently available therapies are not able to stop it. Chondrocyte activation that results in the breakdown of articular cartilage is a key event in the pathogenesis of arthritis. Dr. Sampen’s project will analyze chondrocytes and their response to selected growth factors and cytokines to better understand the mechanisms of cartilage degeneration in osteoarthritis.

Assessing RA Risk at Genetic Level

Hui Wu, M.D., University of California, Los Angeles, CA

Genetic risk factors for RA susceptibility and severity have been widely studied. The main goal of Dr. Wu’s project is to map the gene found to contribute to early RA onset. She is studying specific genes to better understand the genetic difference between early-onset and late-onset RA. Identifying the risk factors may enable scientists to distinguish between those individuals at low risk from those who are at high risk for development of early RA. RA patients at high risk may benefit from early, aggressive treatment to prevent severe joint damage from developing.

Autoimmune Disease inhibited by T Regulatory Cells

Shiguang Yu, Ph.D., University of Missouri, Columbia, MO

Autoimmune diseases arise when the immune system reacts against self tissues or organs.
Low activity or dysfunction of T regulatory cells can cause autoimmune diseases. Dr. Yu’s recent work demonstrated that T regulatory cells make B cell deficient mice resistant to autoimmune disease. The goal of this study is to test whether the depletion of B cells inhibits autoimmune disease by increasing T regulatory cell activity. The information derived from this study will provide clues for modulating the activity and number of T regulatory cells to inhibit autoimmune diseases.

Cartilage Regeneration Study

Li Zeng, Ph.D., Tufts University School of Medicine, Boston, MA
Arthritis is a widespread, debilitating disease in which the joint cartilage slowly disintegrates. One of the possible remedies for this disease is to regenerate cartilage and transplant the regenerated tissue to the affected joint. To regenerate cartilage, we need to have a thorough understanding of the mechanisms of how cartilage is formed from progenitor cells. Many of the signaling events in the regeneration process are similar to tissue formation processes in the embryo. Dr. Zeng’s long-range goal is to reveal the mechanisms that control cartilage formation in the embryo to provide knowledge for treating arthritis through cartilage regeneration.

Grant Recipients a Second Year: The Research Continues

The following scientists have been awarded a second year of funding to continue their work. Each submitted a detailed report outlining the scientific progress made during the first year of their study and competed among all applicants for their grant award.

A New Regulatory Pathway in Autoimmunity

Hongbo Chi, Ph.D., Yale University School of Medicine, New Haven, CT

T lymphocytes, a type of white blood cell, play a central role in the regulation of immune responses against infection and cancer. The function of T lymphocytes is critically dependent upon their ability to distinguish between self and non-self tissues in the body. When this recognition of self-tissues by T lymphocytes goes awry, it leads to many autoimmune diseases such as lupus and rheumatoid arthritis.

Therapeutic intervention of lupus and other rheumatic diseases requires a better understanding of the molecular and cellular pathways regulating T cell function. Dr. Hongbo Chi utilizes a new genetic tool to study this molecular pathway using mouse models, with the long-term goal of translating the knowledge gained into innovative therapies.

The Role of B Cells in RA

Taras Lyubchenko, Ph.D., University of Colorado Health Sciences Center, Denver, CO

Understanding the mechanisms underlying activation of antibody-producing B cells is particularly important in autoimmune diseases such as rheumatoid arthritis. Dr. Lyubchenko’s study will focus on one of the key processes responsible for B cell activation: intracellular signaling mechanisms. He will study intracellular signaling mechanisms in B cells with cutting-edge digital fluorescent imaging techniques. Data generated by this study will help to direct future therapies for targeting signaling molecules to reduce B cell activation and subsequent abnormal activity in rheumatoid arthritis and other autoimmune disorders.

Understanding the Immune System

Adam Mor, M.D., New York University Hospital for Joint Diseases, New York, NY

The immune system is designed to protect us from infection, but when its regulation is impaired it can give rise to diseases in which normal tissues are damaged. Lupus (Systemic Lupus Erythematosus) is the prototype of such a disease. In its final stages, lupus can cause damage in the body’s major organs.

In order to prevent onset of the disease, Dr. Mor is using a lupus mouse model to study the immune system’s defects at the molecular level. Learning the basic molecular pathways in lupus is a crucial step in the development of drugs to treat the disease.

Cartilage Regeneration in OA

Anna Spagnoli, M.D., Vanderbilt University School of Medicine, Nashville, TN

Osteoarthritis affects over 43 million people in the United States. Currently, there is no form of treatment that can prevent, delay the onset, or affect the progression of osteoarthritis. Current therapies only alleviate the symptoms. Cartilage cannot regenerate itself. This has led to efforts to develop alternative means to restore damaged cartilage.

Bone marrow contains stem cells, called mesenchymal stem cells, which are capable of becoming cartilage cells. The goal of Dr. Spagnoli’s study is to determine how mesenchymal stem cells become cartilage. These studies provide a unique opportunity to obtain crucial data essential to fully implement the use of mesenchymal stem cells to prevent or halt the progression of osteoarthritis.

Preventing Bone Loss in RA

Nicole Walsh, Ph.D., Beth Israel Deaconess Medical Center, Boston, MA

The structural integrity of bone is maintained by the coordinated actions of two cell types, the bone-forming osteoblast and the bone-resorbing osteoclast. In rheumatoid arthritis (RA), there is an imbalance in the activities of these two cells, with osteoclast resorption activity predominating. This results in bone loss within the joints leading to joint deformity and pain. The exact mechanisms mediating this imbalance have not been fully explained.

White blood cells, such as T cells, not only contribute to inflammation within the RA joint, but have also been implicated in mediating the formation and function of osteoclasts. Therefore, T cells represent a potential target for therapeutic intervention to prevent arthritis-induced bone loss. In this second year of funding, Dr. Walsh is focusing on defining the role of T cells. A clearer understanding of the mechanisms regulating osteoblast function in RA, and the role T cells play in this, will help identify targets for promoting bone formation, a necessary step in restoring joint function in RA.

Dr. Walsh has been awarded the honor of being named The Sontag Foundation Fellow for 2006-2007, for excellence in research related to rheumatoid arthritis.

Alternative to Immunosuppressive Drugs for Lupus

Song Guo Zheng, M.D., University of Southern California, Los Angeles, CA

Lupus is an autoimmune disease that afflicts approximately 1.5 million American, 90% of whom are women. Although drugs that suppress the immune system can control lupus development, the long-term effects of these drugs are limited and may cause severe side effects.

Certain cells that respond to self tissues or organs exist in healthy humans; however, their activities are controlled by a cell population called regulatory T cells. Dr. Song Guo Zheng is studying the effects of different combinations of regulatory T cells, generating results that will provide guidance to develop the optimal combination of regulatory T cells as therapy for lupus patients.

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The Arthritis National Research Foundation (ANRF), based in Long Beach, California, funds promising young scientists at the beginning of their careers to pursue cutting-edge research for the treatment, cure and eventual end to the suffering of over 66 million Americans with arthritis and its related diseases.

The ANRF provides grant funding for highly qualified researchers associated with non-profit research facilities, universities and hospitals throughout the country. ANRF grant recipients are seeking new knowledge for the prevention, treatment and cure of osteoarthritis, rheumatoid arthritis, and other rheumatic and related autoimmune diseases. For more information on the Arthritis National Research Foundation, call 800-588-2873, e-mail, anrf@ix.netcom.com, or visit the website, www.curearthritis.org.

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