Gut Microbiome and Immune Tolerance in Multiple Sclerosis Treatment

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• Oral Tolerance Explained
• Nasal Anti-CD3 Antibody Therapy
• Gut Microbiome Role in Autoimmunity
• Microbiome Reconstitution for MS
• Future of Bacterial MS Vaccines
• Full Transcript

Oral Tolerance Explained

Oral tolerance is a fundamental immune system process where the body learns to tolerate food antigens entering through the gut. Dr. Howard Weiner, MD, a pioneer in this field, describes it as the gut immune system's critical role in preventing adverse reactions to what we consume. This concept is experiencing a renaissance due to its profound connection to the microbiome and autoimmune diseases like multiple sclerosis.

Dr. Howard Weiner, MD, explains that clinical trials are actively exploring this link. The research focuses on how gut immune responses directly influence the progression and activity of multiple sclerosis in patients. While no specific oral tolerance medications are yet approved, this area represents a major frontier in developing new multiple sclerosis treatments.

Nasal Anti-CD3 Antibody Therapy

Dr. Howard Weiner, MD, is investigating a novel monoclonal antibody called Anti-CD3 as a mucosal therapy. This antibody is administered either orally or nasally to specifically stimulate the mucosal immune system. The goal is to induce immune tolerance, a mechanism that could benefit not only multiple sclerosis but a range of other autoimmune conditions.

The development of this nasal vaccine is progressing through initial clinical trials. Dr. Howard Weiner, MD, highlights its significant promise, particularly for patients with progressive forms of multiple sclerosis. This approach represents a targeted strategy to modulate the immune system directly at its mucosal interfaces.

Gut Microbiome Role in Autoimmunity

The gut microbiome's importance extends to all autoimmune diseases, not just multiple sclerosis. Dr. Howard Weiner, MD, emphasizes that the collection of bacteria in our gut is immense, even outnumbering the body's own cells. Its complexity includes its own circadian rhythms, making it a vast and dynamic ecosystem that is crucial for health.

Research confirms that the gut microbiome in multiple sclerosis patients is abnormal. Dr. Howard Weiner, MD, notes that understanding these microbial differences is key. The next step is to learn how to effectively manipulate this environment to create a therapeutic benefit for patients suffering from autoimmunity.

Microbiome Reconstitution for MS

Microbiome reconstitution, often referred to by patients as fecal transplant, is a serious area of investigation for multiple sclerosis treatment. Dr. Howard Weiner, MD, prefers the more precise term, which involves transplanting a healthy microbial community to reconstitute a patient's gut. He confidently states that this approach will one day be used to help patients with MS.

The concept involves infusing specific, beneficial bacteria directly into a patient's gastrointestinal tract. Dr. Weiner's research is focused on defining what a "normal" microbiome looks like. The ultimate goal is to develop standardized methods to correct the abnormal microbiome found in multiple sclerosis.

Future of Bacterial MS Vaccines

The future of multiple sclerosis treatment may lie in non-pharmacological vaccines based on bacteria. Dr. Howard Weiner, MD, confirms that infusing specific bacteria could indeed function as a true vaccine for MS. This approach leverages the classic principle of using microbial components to train the immune system, but for therapeutic rather than preventive purposes.

This represents a paradigm shift in multiple sclerosis therapy. During his discussion with Dr. Anton Titov, MD, Dr. Weiner expressed great optimism about this progress. The growing knowledge of immune tolerance and the microbiome is paving the way for these innovative and potentially curative treatments.

Full Transcript

Dr. Anton Titov, MD: Let's talk about oral tolerance and microbiome. You pioneered this concept. You also extensively wrote on the subject of oral immune tolerance for several decades. What is oral tolerance? How can oral tolerance be used to treat autoimmune disease? Which patients benefit most from the oral tolerance treatments?

Dr. Howard Weiner, MD: Oral tolerance refers to the fact that we tolerate food that comes into our gut. The gut immune system is very important. There has been a renaissance or resurgence in studying the gut.

Especially there is a renewed interest in studying the microbiome, because that is part of the various bacteria in our gut that relates to immune tolerance. There are a lot of clinical trials going on now that show what happens in the gut can be related to how patients do with their multiple sclerosis.

There are not any specific oral tolerance or microbiome medications yet, but they are being studied. We are studying the microbiome; many researchers are studying it.

We are also studying a monoclonal antibody called anti-CD3. We can give it orally or nasally. This antibody anti-CD3 stimulates the mucosal immune system.

Dr. Anton Titov, MD: How far in the development of the anti-CD3 antibody are you? Because you have been working on it for a while. Anti-CD3 antibody has a lot of promise for diseases, not only for multiple sclerosis but for other autoimmune diseases.

Dr. Howard Weiner, MD: We are now in initial clinical trials in some diseases. We hope to be trying this antibody in progressive types of multiple sclerosis. Anti-CD3 antibody is given nasally.

On the subject of oral tolerance, I spoke to Dr. Simon Robson of Beth Israel Deaconess Hospital. We discussed that gut microbiome has its own cyclical circadian clock. It is very complex.

Gut microbiome is larger than the number of cells of the body. This is very important.

Dr. Anton Titov, MD: What do your clinical trials show? What is the importance of gut microbiome for the general autoimmune diseases? How can it potentially be influenced?

Dr. Howard Weiner, MD: The microbiome is important for all autoimmune diseases. We need to understand gut microbiome more. We need to understand how you can manipulate it to help patients.

Dr. Anton Titov, MD: Fecal transplant is the word that patients hear a lot. Could fecal transplant potentially be used for the multiple sclerosis treatment?

Dr. Howard Weiner, MD: I wouldn't use the word "fecal transplants." I would use the word "microbiome reconstitution." One day we will use fecal transplants and microbiome reconstitution for treatment of multiple sclerosis.

We will reconstitute gut microbiome or do transplants of the microbiome to help patients suffering from multiple sclerosis.

Dr. Anton Titov, MD: Are there any people with certain gut microbiomes that are resistant to multiple sclerosis? Is that something that has been studied?

Dr. Howard Weiner, MD: We are studying it now. We know that the gut microbiome in multiple sclerosis patient is not normal. As we define this, then we will figure out how to make gut microbiome normal.

Dr. Anton Titov, MD: Potentially you can have a certain bacteria that you can inject, infuse into the patient's gut?

Dr. Howard Weiner, MD: That is correct.

Dr. Anton Titov, MD: That will cure multiple sclerosis?

Dr. Howard Weiner, MD: That is correct, yes. That would be a non-pharmacological multiple sclerosis treatment! It is a true vaccine.

Remember, vaccines are using bacteria and viruses in special ways. That would be a vaccine for multiple sclerosis.

Fecal transplant or microbiome reconstitution is investigated for multiple sclerosis treatment. Nasal vaccines based on growing knowledge of immune tolerance development are also being developed as multiple sclerosis therapy. There is a lot of progress in the microbiome and multiple sclerosis research.