Brigham researchers are developing a new method to target autoimmune reactions in the brain using designer bacteria, aiming to make treatments safer and more effective.
Researchers from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, have developed a probiotic to suppress autoimmunity in the brain. This occurs when the immune system attacks the cells of the central nervous system and is at the core of several diseases, including multiple sclerosis. In a new study, researchers demonstrated the treatment’s potential using preclinical models of these diseases. They found that the technique offers a more precise way to target brain inflammation with reduced negative side effects compared to standard therapies. T
“Engineered probiotics could revolutionize the way we treat chronic diseases,” said lead author Francisco Quintana, PhD, of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital. “When a drug is taken, its concentration in the bloodstream peaks after the initial dose, but then its levels go down. However, suppose we can use living microbes to produce medicine from within the body. In that case, they can keep producing the active compound as it’s needed, which is essential when we consider lifelong diseases that require constant treatment.”
Autoimmune diseases impact around 5-8% of the U.S. population. Despite being widespread, there are limited treatment options for most of these diseases. Diseases like MS that affect the brain are especially difficult to treat because many medications can’t effectively reach the brain due to the blood-brain barrier, which acts as a protective barrier between the brain and the circulatory system.
In their search for new treatments for autoimmune diseases, researchers focused on dendritic cells, a type of immune cell found in high numbers in the gastrointestinal tract and around the brain. While these cells regulate the immune system, their specific involvement in autoimmune diseases is not yet fully understood. Through their study of dendritic cells in the central nervous system of mice, the researchers identified a biochemical pathway that these cells use to inhibit other immune cells from attacking the body.
“The mechanism we discovered acts like a brake for the immune system,” explained Quintana. “In most people, it is activated. However, in individuals with autoimmune diseases, there are issues with this braking system, which means the body lacks a way to defend itself from its own immune system.”
The researchers discovered that this biochemical brake can be activated with lactate, a molecule involved in numerous metabolic processes. Then, they successfully genetically engineered probiotic bacteria to produce lactate.
“Probiotics are not new – we have all seen them sold as supplements and marketed as a way to promote health,” said Quintana. “Using synthetic biology to get probiotic bacteria to produce specific compounds relevant to diseases, we can enhance the benefits of probiotics to the maximum.” They tested their probiotic in mice with a disease closely resembling MS and found that, even though the bacteria live in the gut, they could reduce the disease’s effects in the brain. They did not find the bacteria in the bloodstream of the mice, suggesting that the observed effect resulted from biochemical signalling between cells in the gut and in the brain.
“We have discovered in recent years that the microorganisms in the gut have a significant impact on the central nervous system,” said Quintana. “We focused on multiple sclerosis in this study to see if we can use this effect to treat autoimmune diseases of the brain. The results indicate that we can.” Although the current study only looked at the effect of the probiotic in mice, the researchers are optimistic that the approach could be easily adapted for human use because the strain of bacteria used to create the probiotic has already been tested in humans. The researchers are also working to adjust their approach for autoimmune diseases that affect other parts of the body, especially gastrointestinal diseases like inflammatory bowel syndrome.
Quintana and his colleagues are collaborating with Mass General Brigham Ventures to establish a new company. Mass General Brigham is renowned for its leadership in research and innovation, which has led to the formation of numerous companies driving scientific advancement and economic growth locally and globally. These companies allow patients worldwide to benefit from the discoveries made at Mass General Brigham. Quintana stated, “Using living cells as a form of medicine within the body holds great potential for creating more personalized and precise therapies. If the microbes in the gut can impact brain inflammation, we believe we can harness their power for other applications.”