Myasthenia gravis (or myasthenia for short) is a rare disease in which the immune system turns against its own body. Autoantibodies disrupt the transmission of impulses at the interface between nerve and muscle. The result is muscle weakness, which typically increases with physical exertion and improves again at rest.
Paralyzed eyelids, double vision, muscle weakness in the arms and legs and even difficulty swallowing and breathing – these are all typical symptoms of the rare neurological autoimmune disease myasthenia gravis (MG). The neuromuscular transmission disorder is triggered by autoantibodies that inhibit the acetylcholine receptors on the motor end plate. In most patients, the antibodies are formed in the thymus. Up to 80% of patients have a thymus change: Around 65% of patients have thymic hyperplasia and around 10-15% have a thymoma. Binding of the antibodies to the receptor activates the complement system, which leads to destruction of the postsynaptic membrane.
Worldwide, around 2-5% of the population suffer from an acquired or hereditary form of the disease. In Switzerland, it is estimated that there are six patients per 100,000 people. The severity is determined by the respective severity of the symptoms. In around half of myasthenia patients, the disease begins with visual disturbances due to double vision and heaviness of the upper eyelids, in around 14% swallowing and speech disorders occur first and in only 8% of patients is weakness of the arms and legs the first symptom. As the condition progresses, the symptoms can spread and also affect the chewing, swallowing and speech muscles, shoulder girdle, upper arm, pelvic and thigh muscles. Diagnosis is based on clinical tests, laboratory tests to determine antibodies and, if necessary, electromyographic examinations. A CT scan with contrast medium of the anterior upper thorax is also diagnostically important to detect a possible enlargement of the thymus gland, which is significant in myasthenia, or to detect a tumor.
Guideline recommendations and therapeutic intervention options
The current guideline defines (highly) active generalized MG as a disease with, among other things, moderate or high MGFA status and/or at least two recurrent severe exacerbations requiring therapeutic intervention within one year of diagnosis despite adequate course-modifying and symptomatic therapy. Treatment management depends on the antibody status, severity, duration of the disease and the age of the patient. The goal should always be a life free of symptoms for the person affected. In addition to the removal of the thymus gland, various pharmacological interventions are available. In addition to cortisone, azathioprine, mycophenolate mofetil and intravenous immunoglobulins, other preparations are now available or are in the final phase of testing.
Complement inhibitors were the first active ingredient class to be added. While the monoclonal antibody eculizumab has been approved for generalized, AChR-Ak-positive MG with the restriction of treatment refractoryity for several years, another humanized monoclonal antibody against the C5 element of the complement system, ravulizumab, was approved more broadly for generalized myasthenia in 2022. Zilucoplan is another C5 complement inhibitor, albeit a macrocyclic peptide that is currently in the final stages of Phase III.
The humanized monoclonal antibody Efgartigimod, an FcRn modulator, has also been available since 2022. FcRn blockade prevents IgG from binding to the FcRn so that the body can break down the IgG autoantibodies more quickly. Rozanolixizumab, a second representative of this drug class, is currently in Phase III.
But research is also being carried out in other areas. Inebilizumab, mezagitamab, satralizumab, tolebrutinib and CAR-T therapies are currently in development. The latter has now demonstrated its effect for the first time. At the University Medical Center Magdeburg, a 34-year-old female patient suffering from severe myasthenia gravis was successfully treated for the first time worldwide with the novel CAR-T cell therapy as part of an individual treatment trial.
Further reading:
- https://hirnstiftung.org/alle-erkrankungen/myasthenia-gravis-mg (last accessed on 21.11.2023)
- www.muskelgesellschaft.ch/diagnosen/myasthenia-gravis (last accessed on 21.11.2023)
- https://flexikon.doccheck.com/de/Myasthenia_gravis (last accessed on 21.11.2023)
- https://idw-online.de/de/news824365 (last accessed on 21.11.2023)
- www.dgnvirtualmeeting.org/home/dgn/dgn2023/de-DE (last accessed on 21.11.2023)
- www.docinside.ch/neue-therapieoptionen-bei-myasthenia-gravis (last accessed on 21.11.2023)
InFo NEUROLOGY & PSYCHIATRY 2023; 21(6): 32
