Transverse Myelitis Research Funding Leads to NIH Grant
By Hannah Kelly
In 2022, Monique Anderson, MD, PhD was awarded a research grant funded by SRNA’s Pauline H. Siegel Eclipse Fund. This fund supports research that aims to improve the quality of life of patients in our community by better understanding the causes of rare neuroimmune diseases and how to diagnose and treat them.
Working with her mentor Michael Levy, MD, PhD at Massachusetts General Hospital, Dr. Anderson is studying how a certain gene may be related to transverse myelitis. Transverse myelitis refers to inflammation of the spinal cord. The spinal cord sends messages from the brain to the rest of the body. Damage to the nerves of the spinal cord can interfere with these messages getting to and from different parts of the body. This can result in weakness, changes in how things feel, and issues with bowel, bladder, and sexual function.
In his previous work, Dr. Levy discovered a mutation (or change) in the VPS37A gene in eight patients with transverse myelitis. VPS37A makes a protein that is important for recycling and removing proteins from cells. Some of these proteins are placed in the space outside of cells into sacs, some of which are called exosomes. Dr. Levy and Dr. Anderson aren’t yet sure how changes in this process are involved in transverse myelitis. It’s possible that changes in this gene cause proteins to be taken outside of the cell when they aren’t supposed to be. The immune system then might react to this disruption in a way that causes inflammation of the spinal cord. Interestingly, this mutation only seems to increase someone’s risk of monophasic transverse myelitis, meaning these patients only have one attack.
Dr. Anderson’s study is investigating if new markers within exosomes are found in the blood of patients with transverse myelitis. These markers could potentially be used in the diagnosis of transverse myelitis. The researchers also hope to better understand the signaling pathways between cells that trigger an immune response against the spinal cord. The study includes both patients with idiopathic transverse myelitis (meaning no cause has been found yet) and patients with multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody disease (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD). MS, MOGAD, and NMOSD are disorders that also involve inflammation of the spinal cord. Dr. Anderson hopes to determine if there are any shared mechanisms between these diseases and if there are similar proteins within exosomes that the immune system responds to.
In an “Ask the Expert” podcast episode with SRNA, Dr. Anderson explains that, “if there are similar mutations occurring in the different patient populations, that might give us a clue of something that’s…occurring in these similar diseases. So, it gives us an idea of, one, are there additional genetic tests that we should be doing for patients? And two, is this a potential therapeutic target for these patients?” Dr. Anderson also highlights that the signaling pathway being studied is relevant to other neurologic diseases and that she hopes the study will guide future transverse myelitis therapies. In her words, “…that same … pathway has been implicated in several other neurologic disorders especially in the realm of repair and recovery. So, it’s unclear if this is also going to be the case with transverse myelitis, but this is something that we’re hoping to answer as well.”
In 2023, Dr. Anderson and her mentor Michael Levy received an NIH R01 award of $1.25 million to dig deeper into this genetic mutation and potentially identify new targets for therapy. This shows how funding pilot studies and novel ideas lays important groundwork for research, including studies with the potential to discover new therapies for our patients. Better understanding how diseases such as transverse myelitis happen will improve our ability to diagnose, treat, and perhaps prevent them. Thank you to our amazing community for supporting research projects like Dr. Anderson’s through the Pauline H. Siegel Eclipse Fund for Research.
