Charting the Future of Myasthenia Gravis Therapy With Dr. Henry Kaminski
- Alex Carter
- 5 days ago
- 4 min read
Updated: 7 days ago
Myasthenia gravis, a rare autoimmune disorder targeting the junction between nerve and muscle, has long been managed with treatments borrowed from more common diseases. While new therapies offer hope, the hunt for a targeted cure remains a formidable challenge. Leading expert Dr. Henry Kaminski guides us through the latest breakthroughs in treatment, the hurdles of drug development, and the innovative, cross-disciplinary collaborations that may finally unlock personalized care for those living with this complex condition.
In recent human history, breakthroughs in medicinal research have flourished at a rapid rate, putting an end to many deadly diseases that plagued our world in the past, from smallpox and polio to COVID-19. However, much is still unknown about the development and treatment of autoimmune diseases, due to their low prevalence and requirement for highly specialized care. Despite its rarity myasthenia gravis (MG), or “grave muscle”, is among the most well-studied muscular autoimmune disorders currently documented[A]. Henry Kaminski, a leading expert on MG, is a professor of neurology at the George Washington University School of Medicine and Health Sciences.
“Back when I was an undergraduate, I wanted to be a scientist. I was a complete failure on my projects, but despite that I still wanted to do this. After graduating residency, I decided to work with this MD/PhD Neurologist, who made the mistake of giving me a project to write a review article on Myasthenia Gravis. From there [it was fascinating to me], and the rest is history—it continues to be more fascinating as we grow, and now with the collaborations and capabilities I have, [there’s always more we can do].”
An Attack on the Neuromuscular Junction
Autoimmune diseases are characterized by unintended antibody production and activity—targeting and deactivating self-produced, necessary proteins [B]. In the case of MG the antibody types, and therefore, targeted proteins can vary; the overarching determinant of this disease stems from antibodies targeting proteins on the neuromuscular junction (NMJ) within skeletal muscles [C]. This junction is important to facilitate the communication between the brain and the muscles—dysfunction of these junctions can give rise to many symptoms associated with MG, ranging from limited muscle strength and involvement to much more serious problems, such as respiratory failure. As general, nonspecific immunosuppression treatment has long been outdated and associated with increased risk for disease [D], the search for efficient targeted treatment of MG is an ongoing challenge.
“We know what produces it, but there were no treatments beyond things that we took from more common diseases to suppress the immune system.”
Current Strategies: A Double-Edged Sword
Because the mechanisms of MG are pretty well known, new therapies are made to target particular pressure points of the disease. Kaminski highlights a few leading strategies that have been subject to ongoing research: FcRn inhibitors are now commonplace in autoimmune treatment. Under normal circumstances, our bodies have the ability to recycle antibodies in the blood, protecting them from degradation [E]. This process occurs through neonatal Fc receptors—cell surface proteins that antibodies bind to in order to be internalized and processed, before being released back into the bloodstream. Specially developed inhibitors block this process by acting as a competitive inhibitor of the Fc receptor, as a way to ensure malignant antibodies are no longer in circulation. Another strategy, complement inhibition, involves not the targeting of the antibody itself, but the pathway of activation for MG. Rogue antibodies activate a series of enzymatic reactions known as the complement system, the end result forming a protein complex that breaks down important cells within the NMJ [F]. Ultimately, this leads to the destruction of acetyl choline receptors in the muscle, hindering neuromuscular communication [G]. Complement inhibitors seek to stop this process and inhibit the pathway by targeting specific, necessary proteins for its continuation.
However, at the base level, these treatments are nonspecific, an issue Kaminski has attempted to solve in the past. A potential solution involves adding a protein linked to the complement inhibitor drug that targets the neuromuscular junction, which could improve specificity; Kaminski laments on how this project was stopped in its tracks:
“We couldn’t take the next step to optimize this drug. We got a patent to develop this further, but were not able to make this transition. The key in drug development is moving from an established proof of concept to actually ramp up to the drug.”
“[FcRn and Complement inhibitors] don’t cure it, but they’re good to have. Now, we also understand other aspects of the immune system—we can try to wipe out the cells that are producing antibodies. Right now we don’t have a targeted way to eliminate the ‘bad cells’ that produce these antibodies.”
The Next Frontier: Specificity and Personalized Models
An important next step in MG drug development research that Kamiski is working towards involves improving technology that is specific for the cells producing the malignant antibodies. While a clear solution proves to elude scientists, the overarching challenges are evident—specificity is incredibly important, and may be the key doctors need for future treatment—both in the context of targeted therapies, and the development of personalized patient care plans to combat the high complexity of MG. Rapidly growing and improving in not just current clinical research, but all scientific fields, is the utilization of mathematical models to capture data for predicted outcomes of complex problems. This method for developing a specialized treatment course has already proven to be successful in the context of host-tumor interactions for cancer treatment, which reveal how an individual’s immune system reacts to not just the growth of cancerous cells, but continued treatment and immunotherapy [H]. Kaminski believes, working among peers and mathematicians, that these models are the future of more personalized and targeted treatment for MG patients; newer methods such as these have the capability to shed the limitations of previous strategies for combatting MG.
“It offers the opportunity to easily standardize and translate clinical trials. It’s very exciting to have these cross-disciplinary collaborations, and to be able to model these trials to determine patient response to treatment.”
Though challenges in drug development and the elusive goal of eliminating specific antibody-producing cells persist, the combination of deepening mechanistic knowledge and sophisticated predictive tools, spearheaded by Dr. Kaminski, positions the field on the cusp of breakthroughs that could fundamentally change outcomes for patients living with this condition.
