🧠Timeline of MG Breakthroughs
🏛️ Early Recognition (1600s–1800s)
- 1672 – Thomas Willis
- First description of fluctuating muscle weakness (likely MG)
- 1877 – Samuel Wilks
- More detailed clinical description
- 1895 – Friedrich Jolly
- Coined the term “myasthenia gravis”
⚡ Neuromuscular Transmission Era (1930s–1950s)
- 1934 – Mary Broadfoot Walker
- Discovered physostigmine improves MG symptoms
- → First effective treatment
- 1940s–50s
- Understanding of acetylcholine (ACh) and neuromuscular transmission
- Development of edrophonium (Tensilon test) for diagnosis
🧬 Autoimmune Revolution (1960s–1970s)
- 1960 – John Simpson
- Proposed MG is autoimmune
- 1973 – Patrick Lindstrom
- Demonstrated ACh receptor antibodies cause MG
- 1970s
- Discovery of:
- Thymus abnormalities
- Experimental autoimmune MG (EAMG)
- Discovery of:
👉 This era fundamentally changed MG from a “mystery weakness” → defined autoimmune disease
🏥 Treatment Expansion (1980s–1990s)
- Introduction of:
- Plasmapheresis (PLEX)
- IVIG
- Corticosteroids (prednisone)
- Azathioprine
- Thymectomy increasingly used (but evidence still observational)
👉 Shift toward immune-modulating therapy
🧪 Antibody Subtypes Era (2000s)
- 2001 – MuSK antibodies discovered
- 2010s – LRP4 antibodies identified
👉 MG reclassified into:
- AChR-positive
- MuSK-positive
- LRP4-positive
- Seronegative
🏆 Evidence-Based Medicine Era (2010s)
- 2016 – MGTX Trial (James F. Howard Jr. / Gil I. Wolfe)
- Proved thymectomy improves outcomes
- 2016 – International MG Guidelines (Donald B. Sanders)
- Standardized global treatment approach
👉 MG becomes protocol-driven and evidence-based
💊 Biologic Therapy Revolution (late 2010s–2020s)
- 2017 – REGAIN Trial
- Eculizumab (complement inhibitor)
- 2021 – ADAPT Trial
- Efgartigimod (FcRn inhibitor)
- 2020s:
- Ravulizumab
- Rozanolixizumab
- Expanded rituximab use (especially MuSK MG)
👉 Shift to targeted immunotherapy (precision medicine)
🚀 Current & Future Direction (2020s–present)
- Biomarkers for treatment response prediction
- Personalized therapy by antibody subtype
- Exploration of:
- Gene therapy
- Immune tolerance strategies
- Stem-cell models of NMJ
📌 Big Picture Evolution
| Era | Key Shift |
|---|---|
| 1600–1900 | Clinical description |
| 1930–1950 | Symptomatic treatment (ACh-based) |
| 1960–1970 | Autoimmune discovery |
| 1980–2000 | Immunosuppression |
| 2000–2010 | Antibody subtypes |
| 2010–2020 | Evidence-based care |
| 2020–present | Targeted biologics |