Rheumatoid Arthritis Research | Causes of Rheumatoid Arthritis
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Rheumatoid Arthritis Research

Researchers are working to understand what causes rheumatoid arthritis

Rheumatoid arthritis (RA) is a complex disease in which the patient’s immune system attacks its own tissue causing swelling and inflammation in the joints and damage of tissues and other organs. Much of the rheumatoid arthritis research being conducted focuses on immune mechanisms involved. Many of these mechanisms are shared with other autoimmune diseases that attack different organs, such as lupus (kidneys), multiple sclerosis (brain) and Type I diabetes (pancreas). The causes of rheumatoid arthritis are still unknown, but we do know that autoimmune diseases have a start and halt progression, with periods of active disease followed by periods of remission. Thus, thanks to the rheumatoid arthritis research discoveries of Gale “Morrie” Granger, PhD, the human immune system is the primary focus of research.

 

The human immune response consists of three different phases:

 

  1. Initiation phase – recognition of the foreign or self materials
  2. Expansion phase – increase in the number of immune cells and antibodies
  3. Invasion and Tissue Destructive phase – emigration of cells and antibodies into the blood stream and into the target organs to induce inflammation and tissue destruction
Rheumatoid Arthritis Research

Current RA research grant recipients employ innovative approaches and modern technologies to identify, isolate and study the different phases of the immune response involved in rheumatoid arthritis. Scientists are looking at both the cellular and molecular level. We have hope that a new treatment for rheumatoid arthritis can be developed or better yet that a cure can be found.

Research Highlights

“Resident” Cells Targeted for New RA Treatment

Beatrice Bartok, MD at UC San Diego is studying joint tissues from human RA patients and mice. She has discovered how the normal joint cells become altered by the immune attack.

 

Damage in joints of patients with rheumatoid arthritis (RA) is induced by the patient’s immune system attacking its own joint tissues. However, a portion of this damage is caused by “resident” normal cells in the joint that have become altered during and after the immune attack. The altered resident cells undergo abnormal growth and healing which results in scarring, disfigurement and joint immobilization.

 

Potential: Dr. Bartok has discovered how the normal joint cells become altered by the immune attack. Her important findings can lead to the development of new drugs and treatments to block this destructive cellular response, thereby preventing and stopping the progressive destruction of joint tissues in RA patients.

Neutrophils: Potential Target for Preventing RA

Dr. Junxia Wang at the Brigham & Women’s Hospital of Harvard Medical School in Boston has identified the mechanism of how white blood cells called neutrophils leave the blood stream and migrate into joint tissues.

 

Neutrophils are white blood cells which are important for the body’s defense against infectious agents. However, these same cells enter the joint in rheumatoid arthritis in large numbers and over time cause swelling, pain and tissue damage.

 

Potential: The mechanism of the migration of neutrophils into joint tissues may lead to a therapy that will block the migration and subsequent damage to joint tissues. These results can lead to new methods to prevent the onset and control tissue damage in RA and other forms of inflammatory arthritis by blocking the migration of neutrophils into the joint.

New Target for Therapy in RA: Synovial Fibroblasts

Dr. George Kalliolias at the Hospital for Special Surgery in New York uses novel technologies to characterize and understand the role of synovial fibroblasts, resident joint cells that become activated in rheumatoid arthritis, as potential targets for new treatments.

 

None of the existing therapies for RA targets these cells. Dr. Kalliolias’ studies have shown that synovial fibroblasts display an uncontrolled inflammatory response to factors found in abundance within the inflamed joint of RA patients. These findings led to the hypothesis that these cells in the RA joint lack the appropriate “brakes” that should turn off inflammatory responses.

 

Potential: Dr. Kalliolias is testing this hypothesis to identify strategies to terminate or block the production of inflammatory and tissue destructive mediators by synovial fibroblasts which he hopes will lead to a new therapy targeting these cells.

Other Notable Rheumatoid Arthritis Research Studies Funded By The Foundation

Initiation Phase studies

 

These studies seek to understand and perhaps stop the immune response at its inception.

  • Thomas Morrison, PhD at University of Colorado, Denver is studying the mechanism of how viruses can cause rheumatoid arthritis
  • Result: These studies can result in methods to inhibit the infection and block the products that induce arthritis.

 

  • Joyce Wu, PhD, now established in her own laboratory at the University of Arizona, is studying the role of a specific strain of intestinal bacteria that can activate regulatory cells of the immune system and induce the onset of RA in animals.
  • Result: The possible role of intestinal bacteria to induce RA is a very important finding and could lead to new methods of prevention and a treatment for rheumatoid arthritis.

 

  • Elaine Lourenco, PhD at UCLA is conducting RA research on the regulatory cells that permit the immune system to identify a patient’s own tissues as “foreign” and begin the expansion and attack processes.
  • Result: If these initial cells can be controlled, removed or blocked, the process of auto immunity may be prevented from starting.

 

Expansion Phase studies

 

In patients with rheumatoid arthritis, once the initial immune cells identify the patient’s own tissues as “foreign”, they undergo a period of rapid cell division, or “expansion.” In the effort to find what causes rheumatoid arthritis, scientists have identified that specific cells and multiple cytokines may be involved in this complex process.

 

  • Sujata Sarkar, MD at University of Arizona is studying what induces and maintains the regulatory cells that control the expansive phase
  • Result: Control of these cells would be “switch off” to stop and control the immune response, preventing the “start and halt” cycle of inflammation and damage ongoing in these diseases.

 

  • Candace Cham, PhD at Stanford has found a cytokine released by regulatory cells stimulates this phase and is developing methods to block its action.
  • Result: A material that blocks this cytokine could stop the “start and halt” cycle of inflammation and damage ongoing in rheumatoid arthritis and related autoimmune diseases.

 

  • Richard Di Paolo, PhD at Saint Louis University in Missouri is using an animal model to transplant normal immune cells which stop this phase and block the onset of rheumatoid arthritis. He is also attempting to employ theses transplants to inhibit the ongoing disease.
  • Result: These studies provide new insight to the mechanisms of how the regulatory cells function and may allow control of these important cells to stop the onset of the disease.

 

Invasion and Tissue Destructive Phase

 

In this third phase of the immune response, investigation into processes that cause tissue damage is directed at developing treatment for rheumatoid arthritis. Focusing on alleviating symptoms and stopping the damage from progressing.

 

  • Chuanju Liu, PhD at New York University has identified an important growth factor that promotes tissue healing and also blocks TNF activity.
  • Result: This factor holds great promise for further development as a new candidate for clinical testing. It would be very beneficial in that it could both halt disease and promote healing.

 

  • Sougata Karmakar, PhD at University of Massachusetts, Worchester, has identified cytokine(s) that appear to control the cells that form and destroy bone.
  • Result: These cytokines could be very useful in blocking and repairing bone destruction in RA.

 

  • Xueding Wang, PhD, of University of Michigan is developing new, cutting-edge imaging techniques utilizing tomography and lasers to provide images of soft tissues in joints in RA.
  • Result: The new imaging technique has proven effective for early detection of RA for earlier treatment, as well as monitoring the delivery of drugs used to treat the disease.