Type of article: Research news
Reading time: 3 minutes
Jessica Desamero, PhD
Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system. In MS, the immune system mistakenly attacks and eats away at the protective covering of nerves1. This nerve damage would cause the brain and body to have trouble communicating. Because of this, MS is potentially debilitating. In fact, 50% of MS patients will need help walking within 15 years of disease onset. Therefore, developing novel strategies to treat this disease is vital.
In past clinical studies, omega-3-rich diets increased the quality of life for MS patients. Therefore, omega-3 endocannabinoids (eCBs), which are products of food-derived fatty acids, may help treat MS. However, it is still unclear how.
In a fairly recent study published in the Journal of Biological Chemistry, researchers at the Georgia Institute of Technology and University of Illinois Urbana-Champaign showed how eCBs play a role in modulating T-cell activity and reducing MS symptoms in mice. For their studies, they used preclinical MS mouse models undergoing Relapsing-Remitting Experimental Autoimmune Encephalomyelitis (RR-EAE).2 RR-EAE is a condition where the immune system attacks the brain and causes brain inflammation3.
In a past study published in 2017, Aditi Das, a professor at Georgia Tech, found that eCBs reduced inflammation in samples obtained from rat brain tissues and human blood. She next wanted to perform studies with animal models and decided to use MS mice models.
In the 2023 study, Das and her team focused on a derivative of the omega-3 fatty acid, docosahexaenoic acid (DHA). This derivative is docosahexaenoyl ethanolamide (DHEA). DHA has anti-inflammatory properties, and previous studies suggest that a DHA-based diet may help slow MS progression. Therefore, DHEA may be a key agent in treating MS more naturally. “The molecule that we’re using is not a targeted drug…It’s a diet-derived molecule that can help,” Das said.
Helper T-cells are immune cells that play a role in MS progression and RR-EAE induction. To investigate how DHEA affects helper T-cell activity, the team first explored how T-cells respond to DHEA in vitro. They isolated spleen cells from a T-cell receptor transgenic mouse line, treated these cells with DHEA and then monitored T-cell polarization, or the differentiation of T-cells into proinflammatory subsets. They found that DHEA suppressed T-cell polarization without affecting cell viability. This suggests that DHEA may be able to suppress inflammatory diseases.
Later, they explored how DHEA affects the progression of RR-EAE in mice. Here, they induced RR-EAE in mice and treated them with DHEA either at day zero or at the peak of disease. Then they analyzed disease severity based on clinical scores and weight change. “We showed that DHEA can delay the onset as well as the rate of relapse [of RR-EAE] in the multiple sclerosis animal models…That was the most exciting part of the study,” Das said.
The team concluded that DHEA suppresses T-cell responses, both in vitro and in vivo, and reduces inflammation severity in RR-EAE mice. “A key strength of this research is the use of both cell culture and basic animal models in support of their findings,” said Christopher O’Brien, a neuroscience PhD graduate of Rutgers University-New Brunswick who studied stress and opioid abuse susceptibility in mice.
Das’s study suggests that omega-3 endocannabinoids can ultimately serve as effective diet-based agents for MS therapy. “In concert with other medications, this could be very powerful in helping to mitigate symptoms and improve quality of life,” O’Brien said.
Soon, Das plans to test other DHA derivatives and their effects on other immune cells, like B cells. She also wishes to investigate how to stabilize the rapidly metabolizing eCBs in the body.
Dr. Aditi Das and Dr. Christopher O’Brien were interviewed for this article.
Header Image Source: Wikimedia Commons
References:
1. Goldenberg MM. Multiple Sclerosis Review. P T. 2012;37(3):175-184.
2. Kim JS, Soto-Diaz K, Bingham TW, Steelman AJ, Das A. Role of omega-3 endocannabinoids in the modulation of T-cell activity in a multiple sclerosis experimental autoimmune encephalomyelitis (EAE) model. Journal of Biological Chemistry. 2023;299(2). doi:10.1016/j.jbc.2023.102886
3. Gole S, Anand A. Autoimmune Encephalitis. In: StatPearls. StatPearls Publishing; 2024. Accessed February 29, 2024. http://www.ncbi.nlm.nih.gov/books/NBK578203/
Jess Translating Science 
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