Gregory Wu, MD, PhD, on TRPV4 Expression in Multiple Sclerosis

It is currently unknown how Transient Receptor Potential Vanilloid 4 (TRPV4) contributes to inflammatory responses in the central nervous system (CNS). New research presented at ACTRIMS 2019 examined the expression of TRPV4 in innate immune cells and determined the contribution of TRPV4 during experimental autoimmune encephalomyelitis (EAE).1

Lead author and presenter of this research at ACTRIMS Forum 2019, Gregory Wu, MD, PhD—who is an associate professor of neurology in the Division of Adult Neurology at the Washington University School of Medicine in St. Louis—answered our questions about his important research.

NEUROLOGY CONSULTANT: Can you give us some more background on your study and its findings?

Gregory Wu: We began this work in collaboration with Dr Hongzhen Hu and his lab at the Center for the Study of Itch at Washington University in St. Louis based on their observation that TRPV4—a channel thought to be expressed in the central nervous system (CNS) mainly by neurons—is expressed by microglial cells. We explored the functional contributions of TRPV4 by microglia to CNS inflammation.

NEURO CON: What significance do TRPV4 channels hold in patients with MS?

GW: This is potentially a very important question. Th answer to this question remains unclear at the moment. We have observed expression of TRPV4 in MS brain tissue and are actively seeking to determine whether monocytes in patients with MS might exhibit abnormalities that are based on abnormalities in TRPV4.

NEURO CON: How might these findings improve the future of MS care?

GW: Our ultimate goal is to establish the potential for TRPV4 as a therapeutic target for MS. There are a variety of pharmaceutical reagents available that target TRPV4. Based on our preliminary data, we hypothesize that TRPV4 inhibition will ameliorate disease in the animal model of MS. Our goal is to develop a means of pharmacologically regulating the systemic and local inflammatory responses involved in CNS myelin destruction during MS. One optimistic possibility is that use of a medication that is specific to TRPV4 would be beneficial either for symptoms or for control of disease. It should be noted, though, that our results are preliminary at the moment, so we are being cautiously optimistic.

NERUO CON: Were any of your findings surprising?

GW: The biggest surprise for us was the finding that TRPV4 is so clearly expressed by microglia and that this expression leads to functional use of TRPV4 in microglia. This exciting observation that TRPV4 is used by microglia is conceptually appealing  given that calcium signaling in microglia could open up an important line of investigation and potential treatment aspects of MS.

NEURO CON: What is the next step in your research?

GW: Overall, we are pursuing the basic characterization of potential roles of TRPV4 in neuroinflammation. This will involve different models for MS as well as other neurologic diseases. As I discussed in my talk, we are pursuing the following future directions:

We are trying to determine the cellular basis of TRPV4-mediated neuro-immune interactions in the CNS (meaning, how is TRPV4 relevant in a complex disease state since it is potentially utilized by numerous different immune cells including microglia as well as monocytes). We are working to determine the therapeutic effect of TRPV4 inhibition during EAE as noted previously. We are also exploring the functional contribution of TRPV4 in microglial immune function during EAE and will continue to work on what happens in microglia once TRPV4 is activated. Finally, and perhaps most importantly, we are continuing our assessment of TRPV4 functional expression in human immune cells and MS lesions.


  1. Wu GF, Feng J, Archambault A, Yang Pu, Hu H. Transient receptor potential vanilloid 4 (TRPV4) channels are expressed by microglia and modulate neuroinflammation. Presented at: Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2019; February 28-March 2, 2019: Dallas, TX.