Title: Targeting Autoimmunity in the Brain: Breakthrough Study Reveals Potential of Designer Bacteria for Effective and Safer Treatment
Brigham researchers have made significant progress in their quest to tackle autoimmunity in the brain, leveraging innovative designer bacteria to develop a safer and more effective treatment. Autoimmunity in the brain, characterized by the immune system attacking the central nervous system, is at the core of challenging diseases like multiple sclerosis. The researchers’ pioneering study showcases the potential of their approach, demonstrating improved precision in targeting brain inflammation with fewer negative side effects compared to existing therapies. Published in Nature, these groundbreaking findings offer hope for patients seeking long-term treatment for chronic autoimmune conditions.
Francisco Quintana, PhD, from the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital, expressed his optimism about the potential of engineered probiotics to revolutionize chronic disease treatment. The conventional pattern of drug concentration peaking after administration and eventually diminishing is inadequate for lifelong diseases that necessitate continuous treatment. However, employing living microbes to produce medicine within the body ensures a sustained supply of the active compound whenever needed.
Autoimmune diseases affect around 5-8% of the US population, posing significant challenges due to limited treatment options. Treating autoimmune diseases that specifically impact the brain, like multiple sclerosis, presents additional complexity as many drug therapies struggle to penetrate the blood-brain barrier, a protective mechanism separating the brain from the circulatory system.
To explore novel approaches for treating autoimmune diseases, the research team focused on dendritic cells, a type of immune cell abundant in the gastrointestinal tract and brain spaces. These cells play a crucial role in modulating the immune system, although their involvement in autoimmune diseases remains to be fully understood. Through their analysis of dendritic cells in the central nervous system of mice, the researchers identified a biochemical pathway utilized by these cells to prevent immune attacks on the body.
Quintana explained that this biochemical pathway acts like a brake for the immune system. While it is typically activated in healthy individuals, those with autoimmune disorders face issues with this defensive mechanism, leaving their bodies defenseless against their own immune system.
In the course of their study, the researchers discovered that lactate, a molecule involved in various metabolic processes, could activate this biochemical brake. Exploiting this knowledge, they genetically engineered probiotic bacteria capable of producing lactate.
While the bacteria were cultured in the gut, they demonstrated the ability to mitigate the effects of a disease closely resembling multiple sclerosis in the brain. Intriguingly, the bacteria were not detected in the bloodstream, indicating that the observed effects were a result of biochemical signaling between cells in the gut and brain.
Extending the potential beyond mice, the researchers believe their approach can be translated successfully to human clinical trials. The strain of bacteria used to create the probiotic has already undergone human testing, further bolstering their optimism. Additionally, the team is actively working to adapt their approach for autoimmune diseases affecting other parts of the body, with a particular focus on conditions like inflammatory bowel syndrome.
Excitingly, Quintana and his team are collaborating with Mass General Brigham Ventures to establish a company that will help further develop and commercialize their groundbreaking research. As one of the world’s leading institutions in research and innovation, Mass General Brigham has been the birthplace of numerous companies that have contributed to scientific advancements and economic growth in Massachusetts and beyond, ultimately benefiting patients worldwide.
Harnessing the power of living cells as a source of localized medicine holds tremendous promise for more personalized and precise therapies. Leveraging the profound connection between gut microbes and the central nervous system, the researchers are confident that this breakthrough could have broader implications for treating autoimmune diseases across various body systems.
Disclaimer: The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Brigham and Women’s Hospital or Mass General Brigham.
