Developing an animal model of a disease can play an important role in both helping researchers to better understand that disease, as well as identifying and testing potential therapeutics. Animal models allow scientists to recreate specific elements of human disease, providing a controlled environment through which researchers can study disease mechanisms, how the disease progresses, and how the body might respond to treatment. Tokyo Medical and Dental University (TMDU) recently shared that its researchers had developed a murine (rodent) model of a rare condition called anti-MDA5 antibody-positive dermatomyositis.
This condition is considered an autoimmune disease, meaning that there is some dysregulation of the immune system. In autoimmune diseases, the body mistakenly attacks a part of itself. For example, in this form of dermatomyositis, the body develops autoantibodies against melanoma differentiation-associated protein 5 (MDA5). MDA5 is primarily found within the cell’s cytoplasm. When the body creates autoantibodies against MDA5, the immune response can have a significant negative impact on the skin and lungs.
In their research article, published in PNAS, the research team sought to understand what immune system components drove disease development and progression. To begin, the researchers triggered anti-MDA5 autoantibody production in mice. They found that this did increase lung inflammation but did not contribute to the development of interstitial lung disease. Next, the researchers induced acute lung injury through intranasally administering polyinosinic-polycytidylic acid to the mice. This mimics viral infection in humans. Viruses are thought to be a trigger for anti-MDA5 antibody-positive dermatomyositis. The research team found that:
“The MDA5-immunized mice developed fibrotic ILD representing prolonged respiratory inflammation accompanied by fibrotic changes 2 weeks after [administration], while the control mice had quickly and completed recovered from the respiratory inflammation.”
Once they prompted this reaction, the research team then evaluated which particular immune responses were happening and how they drove disease. They found that:
- CD4-positive T cells increased lung damage and catalyzed ILD development. When the research team reduced CD4-positive T cell counts, lung damage fell.
- A signaling molecule called interleukin-6 (IL-6) was also heightened for a prolonged period of time. When the research team treated the mice with anti-IL-6 receptor antibodies, the mice stopped developing ILD. This suggests that IL-6 inhibitors could be beneficial for people with interstitial lung disease, though more research is needed.
About Anti-MDA5 Antibody-Positive Dermatomyositis
Anti-MDA5 antibody-positive dermatomyositis is a subtype of dermatomyositis. Doctors aren’t exactly sure what causes this rare systemic autoimmune disease. Infections have been linked to anti-MDA5 antibody-positive dermatomyositis as a potential trigger. People with this condition may present with symptoms such as:
- Palmar papules (papules on the palms of your hands)
- Distinctive skin rashes
- Skin ulceration
- Arthritis
- Peripheral lymphopenia (a lower level of peripheral lymphocytes in the blood)
- Rapidly progressive interstitial lung disease (ILD)
As a 2023 article in Nature Reviews Dermatology explains:
MDA5-DM shows a poor response to conventional glucocorticoid and immunosuppressant therapy and has a poor overall prognosis.
Currently, there is an urgent need for research to identify potential treatments for anti-MDA5 antibody-positive dermatomyositis. Available therapies are usually ineffective, leading to a high mortality rate. It is important to begin working towards achieving better outcomes.
