Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.
If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.
This week’s study is…
CXCL5 administration dampens inflammation and improves survival in murine lupus via myeloid and neutrophil pathways
We previously published about this research in a story titled “Balancing CXCL5 Levels Could Potentially Treat Lupus” which can be found here. The study was originally published in the academic journal Arthritis & Rheumatology. You can read the abstract of the study here.
This research team was affiliated with the Singapore General Hospital.
What Happened?
Systemic lupus erythematosus, often just called lupus, is an autoimmune disease with an unclear origin. While treatments have been developed that can help control symptoms, not all patients respond to the available therapies. Therefore, there is still a need for more effective treatments, or even a cure, to be developed.
In this study the research team decided to evaluate a protein called CXCL5, which is known to play a role in the regulation of the immune system through the neutrophils, which are a form of white blood cell. The scientists discovered that in people living with lupus, the levels of this protein in the blood were substantially lower than in people that were disease free. The team found similar data in a mouse model of the disease. The researchers wondered if the low levels somehow contributed to the disease mechanism or symptoms.
The team scientists continued their work with the lupus mouse model and began injecting mice with severe disease with doses of CXCL5. This approach appeared to restore CXCL5 to regular levels; furthermore, survival of the sick mice was improved from 25 percent at 10 weeks to greater than 70 percent. The treated mice displayed reduced disease activity overall and improvements in the function of their kidneys.
The researchers treated some lupus mice with both CXCL5 supplementation and cyclophosphamide, a powerful immunosuppressant. When given in combination, CXCL5 appeared to mitigate the side effects of cyclophosphamide, which allowed the mice to live for up to two years. Administration of CXCL5 appeared to be safe, with no apparent toxicity appearing in the mice. Overall, this research appears to have discovered a possible therapeutic approach for lupus.
About Systemic Lupus Erythematosus
Systemic lupus erythematosus, more commonly known simply as lupus, is an autoimmune disease that is characterized by a red facial rash. An autoimmune illness is one in which the body’s own immune system begins to damage healthy tissue. Certain drugs can induce the disease, but it is most commonly caused by a combination of certain genetic variants, which, when exposed to an environmental trigger, can cause symptoms to begin. Symptoms of lupus include facial rash, swollen, painful joints, fatigue, fever, swollen lymph nodes, chest pain, hair loss, and mouth ulcers. Women are more frequently affected than men. The disease tends to appear in a relapsing-remitting pattern of symptoms. Its symptoms are often vague at first, making diagnosis of lupus more difficult. Treatment may include avoiding sunlight, immune system suppressing drugs, and pain medication. Most people with lupus are able to control their disease effectively without overall lifespan being affected. To learn more about systemic lupus erythematosus, click here.
Why Does it Matter?
These findings could have substantial implications for the future treatment of people living with lupus:
“We are excited about the possibility of a new treatment option for lupus as 30 to 60 percent of patients do not respond to conventional medications despite aggressive regimens. In the past 65 years, only three drugs for lupus have been approved by the United States Food and Drug Administration but these drugs have modest efficacy. There is therefore a real and urgent need for better therapies, particularly for the more severe spectrum of lupus that we see in Asia.” – Andrea Low, Senior Study Author, Associate Professor, Head and Senior Consultant, Department of Rheumatology & Immunology, Singapore General Hospital
The research team hopes to continue this avenue of research so that CXCL5 can one day become an approved treatment for the disease:
“It is gratifying to see that this research that started over 8 years ago, has led to a discovery that has the potential to offer patients with lupus new treatment options in future.” – William Hwang, Professor, Senior Consultant, Department of Hematology, Singapore General Hospital
Lupus tends to be more severe in people of Asian descent, so the findings have special relevance for Singapore and the surrounding region. Only further study will determine if CXCL5 turns into a breakthrough therapy for this autoimmune disease.
