Engineered Probiotic Developed to Treat Multiple Sclerosis

Researchers from Brigham and Women’s Hospital  have designed a probiotic to suppress autoimmunity in the brain, which occurs when the immune system attacks the cells of the central nervous system. Autoimmunity in the brain is at the core of several diseases, including multiple sclerosis. 

“When a drug is taken, its concentration in the bloodstream peaks after the initial dose, but then its levels go down. However, if we can use living microbes to produce medicine from within the body, they can keep producing the active compound as it is needed, which is essential when we consider lifelong diseases that require constant treatment.” said lead author Francisco Quintana, PhD

To look for new ways to treat autoimmune diseases, the researchers studied dendritic cells, a type of immune cell that is abundant in the gastrointestinal tract and in the spaces around the brain. These cells help control the rest of the immune system, but scientists don’t yet know their role in autoimmune diseases. By analyzing dendritic cells in the central nervous system of mice, they were able to identify a biochemical pathway that dendritic cells use to stop other immune cells from attacking the body.

“The mechanism we found is like a brake for the immune system,” said Quintana. “In most of us, it’s activated, but in people with autoimmune diseases, there are problems with this brake system, which means the body has no way to protect itself from its own immune system.”

The researchers found that this biochemical brake can be activated with lactate, a molecule involved in many metabolic processes. The researchers were then able to genetically engineer probiotic bacteria to produce lactate.

They tested their probiotic in mice with a disease closely resembling MS, and they found that even though the bacteria live in the gut, they were able to reduce the effects of the disease in the brain. They did not find the bacteria in the bloodstream of the mice, suggesting that the effect they observed was a result of biochemical signaling between cells in the gut and in the brain.

While the current study only examined the effect of the probiotic in mice, the researchers are optimistic that the approach could be readily translated into the clinic because the strain of bacteria they used to create their probiotic has already been tested in humans. The researchers are also working to modify their approach for autoimmune diseases that affect other parts of the body, particularly gut diseases like inflammatory bowel syndrome.

Sources:

Liliana M. Sanmarco, Joseph M. Rone, Carolina M. Polonio, Gonzalo Fernandez Lahore, Federico Giovannoni, Kylynne Ferrara, Cristina Gutierrez-Vazquez, Ning Li, Anna Sokolovska, Agustin Plasencia, Camilo Faust Akl, Payal Nanda, Evelin S. Heck, Zhaorong Li, Hong-Gyun Lee, Chun-Cheih Chao, Claudia M. Rejano-Gordillo, Pedro H. Fonseca-Castro, Tomer Illouz, Mathias Linnerbauer, Jessica E. Kenison, Rocky M. Barilla, Daniel Farrenkopf, Nikolas A. Stevens, Gavin Piester, Elizabeth N. Chung, Lucas Dailey, Vijay K. Kuchroo, David Hava, Michael A. Wheeler, Clary Clish, Roni Nowarski, Eduardo Balsa, Jose M. Lora, Francisco J. Quintana. Lactate limits CNS autoimmunity by stabilizing HIF-1α in dendritic cells. Nature, 2023; DOI: 10.1038/s41586-023-06409-6

Brigham and Women’s Hospital. “Engineered probiotic developed to treat multiple sclerosis.” ScienceDaily. ScienceDaily, 9 August 2023. <www.sciencedaily.com/releases/2023/08/230809130602.htm>.

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