What is immunology?
Immunology is the study of the immune system, a combination of multiple cell types, proteins, and other systems that protect the body from external and internal threats. It is responsible for clearing viruses such as the common cold or flu and fighting cancer. In addition to defense, the immune system is an essential component of tissue repair and even plays a role in brain development.
Why immunology and ALS?
Some aspects of the immune system are shown to increase the rate at which disease progresses, while other effects are actually protective and can slow disease progression. Robert A. Epstein and Joan M. Chernoff-Epstein Emerging Scholar Benjamin Murdock, Ph.D., heads up this work, whose goal is to determine how the immune system affects ALS to identify viable therapeutic targets. We are trying to address two fundamental questions.
1) How does the immune system affect ALS progression?
2) What can we do to change it?
One of the benefits of immune-based treatments is that hundreds of existing drugs have already been developed. Some are currently in use for other diseases, but many were developed but did not impact the disease they were designed for and may be effective in treating ALS. In addition, targeting the immune system has the added benefit that the drug doesn't have to cross the blood-brain barrier because it targets cells in the bloodstream. Lower doses are required, and it is easier to administer them...in other words, they have the potential to be safer and less expensive.
Key Initiatives:
Immune Markers in ALS Blood:
Our most significant initiative is the overarching analysis of immune markers in the blood of ALS patients. In ALS, these cells become activated and migrate into the spinal cord, affecting disease progression. By studying these markers, we aim to determine which immune cells contribute to disease and identify therapeutic targets.
We have found that several types of immune cells are altered in ALS and that changes in these cells are associated with disease progression rates. We have also found that many of these associations vary based on ALS patient demographics, so we now also believe that the immune system's impact may differ based on whether a patient is younger or older or whether they are a man or a woman. We and others now suspect that one of the reasons that so many ALS clinical trials have failed is that the underlying mechanisms contributing to ALS may vary from patient to patient, so a one-size-fits-all approach to drug treatment may not work—precision, targeted therapies may be necessary in the future.
Neutrophils:
Through investigating immune markers in ALS, one of the newest projects is a more in-depth examination of a cell type called neutrophils and their role in driving ALS. This project is being spearheaded by a Ph.D. student in the lab, Lillia Baird.
Re-Purposing Drugs for ALS:
We are trying to repurpose existing immunology drugs for use in ALS. For the last several years, we have been experimenting with tofacitinib, an immunosuppressant currently used to treat rheumatoid arthritis. The drug targets NK cells, another immune cell believed to play a part in ALS progression.
We have found that the drug is effective in vitro (tested in a dish), and we have recently found that lower doses of the drug significantly improve the lifespan of ALS preclinical models. Here we did observe some sex differences, with male and female mice responding differently to the drug. We will continue to work towards a clinical trial in hopes the drug might slow ALS progression.
