Description and Symptoms

• Myasthenia Gravis (MG) is an autoimmune disease where antibodies act against "the postsynaptic membrane of the neuromuscular junction," which causes muscle weakness and fatigue.
• Juvenile Myasthenia Gravis (JMG) is the same autoimmune disease but happens during childhood and its symptoms differ from adult MG. JMG is the most frequent (75% of cases) and is caused by a "blockade of ACh receptors". It affects children between 0 and 19 years old but is more frequent in children between 2 and 5 years old. Before the symptoms appear, children present a "healthy psychomotor development," and it may be "preceded by an infection."
•  Common symptoms of JMG include ptosis (associated with unilateral or asymmetric ophthalmoplegia, strabismus, and lid twitch, which may cause amblyopia), generalized muscle weakness, dysphonia, dysphagia, and proximal limb weakness. Weakness is more pronounced throughout the day and improves with rest. Children are at risk of choking, aspiration, and chest infection. A "myasthenic crisis," or the impairment of the respiratory muscles, may need ventilatory support.
• Prepubertal children "have a higher prevalence of isolated ocular symptoms, lower frequency of acetylcholine receptor antibodies, and a higher probability of achieving remission."
• JMG is a rare disorder in children, which incidence and prevalence vary geographically. It has been observed that the disease is more common in Oriental countries.
• In children, MG commonly appears either as Ocular Myasthenia Gravis (OMG), where weakness is present "only in the eyelids and surrounding tissue," or as Generalized Myasthenia Gravis (GMG), where "various tissues throughout the body are affected."

Ocular Myasthenia Gravis (OMG)

• Ocular Myasthenia Gravis (OMG) is MG presented only in the oculomotor muscles "for 2 years without becoming generalized."
• OMG in children has an incidence of 3 to 9.1 cases per million each year and presents "mostly in Asian children." In 90% of the cases, children show ocular alterations such as ptosis and ophthalmoplegia, which are associated with systemic symptoms.
• This particular MG has a female-to-male ratio of 1.3:1 and "should be considered as a differential diagnosis" in cases of ptosis or strabismus, as ophthalmological symptoms can vary from ptosis, which is the main sign in patients with strabismus.
• Children with OMG that are treated with different protocols and follow-ups have lower rates of later presenting GMC than adults.

Common Treatments

•  Acetylcholinesterase inhibitors are the main treatment for JMG and provide symptomatic relief. In mild cases and some cases of OMG, this treatment may be sufficient. Pyridostigmine is the most common drug used in this treatment.
• Another treatment includes thymectomy, which may "remove thymic germinal centers and disrupt antibody diversification." This treatment increases the probability of remission and improvement of symptoms in AChR seropositive, nonthymomatous, autoimmune MG. However, its use for OMG is in doubt as it is not proven that it reduces the risk of the disease's progression to generalized JMG.
• Immunosuppressive therapy is also an option for treating JMG. This treatment involves the use of steroids in combination with a steroid-sparing immuno-suppressant, like azathioprine. However, children are may be at risk of experiencing steroid side effects, such as "growth failure, susceptibility to severe infections, and delay in receiving live vaccinations."

Top Doctors Treating Juvenile Myasthenia Gravis

• Some of the top doctors diagnosing and treating JMG include John Brandsema, Thane Blinman, MD, and Grant Liu, MD, all of which are part of the Children’s Hospital of Philadelphia's MG treatment team and have extensive experience treating the disease.
• As there is no publicly available pre-compiled list of top physicians that diagnose and treat JMG, we selected these doctors because there is evidence of their vast experience and they have been featured in scientific articles that talk about the successful treatment of the disease.

Active Trials for Juvenile Myasthenia Gravis

• This trial, conducted by Alexion Pharmaceuticals, is currently on Phase 3. Its purpose is to test "the efficacy, safety, pharmacokinetics, and pharmacodynamics of eculizumab" for treating refractory gMG in pediatric patients. The study includes participants aged 6 to 17 years old.
• The trial is being held in Florida, Illinois, Missouri, North Carolina, Ohio, Pennsylvania, and South Carolina.
• Alexion Pharmaceuticals has not yet reported any initial results regarding this trial.

Active Trials for Myasthenia Gravis in Adults

• This clinical trial is currently on Phase 2 and is conducted by Ra Pharmaceuticals. The trial aims to test the safety and efficacy of RA101495 (zilucoplan) in treating patients with generalized Myasthenia Gravis.
• The trial accepts participants aged 18 to 85 years old. It is being held in Alabama, California, Connecticut, District of Columbia, Florida, Illinois, Kansas, Maryland, Massachusetts, Michigan, New York, Tennessee, Texas, North Carolina, Ohio, Pennsylvania, Utah, Vermont, and Wisconsin.
• In Phase 2 of this trial, Ra Pharmaceuticals found that "near-complete complement inhibition was associated with a faster onset and greater magnitude of a benefit than submaximal complement inhibition," and they observed "favorable safety and tolerability" to zilucoplan. Also, after 12 weeks, patients treated with zilucoplan had significant improvement in both QMG and MG-ADL compared to people given a placebo.

• The University of Alberta, alongside CSL Behring, is conducting Phase 3 of a clinical trial that has the purpose to test the "efficacy, safety, feasibility, and tolerability of SCIG in patients with worsening MG" and to test the drug as an alternative therapy to IVIG.
• Persons aged 18 to 80 are eligible for this study, which is being conducted in Alberta and British Columbia in Canada. Since CSL Behring is headquartered in the US, we are considering this trial to have a US focus.
• In 2017, the first 20 patients "showed a significant reduction in the QMG score by 5.12 points," which indicates that the treatment may be effective for the treatment of worsening MG.

• This trial is being conducted by Argenx BVBA and aims to test the "efficacy, safety, tolerability, quality of life, and impact on normal daily activities of ARGX-113 (efgartigimod)" for the treatment of patients suffering from Generalized Myasthenia Gravis.
• The study accepts participants aged 18 and older and its locations include Arizona, California, Colorado, Florida, Iowa, Kansas, Massachusetts, Michigan, New York, North Carolina, Ohio, Oregon, South Carolina, Texas, Virginia, and Washington.
•  Phase 1 and Phase 2 trials showed that efgartigimod safely dropped autoantibody levels and allowed a "fast and clinically meaningful reduction in disease severity."

• This study, conducted by DAS-MG, Inc., is currently on Phase 2 and aims to test the effectivity of DAS-001 (ondansetron + pyridostigmine) for the treatment in patients with a diagnosis of anti-AchR antibody positive myasthenia gravis.
• The trial accepts persons aged 18 years or older. It is located at George Washington University.
• DAS-MG, Inc. has not yet provided initial results for this trial.

Research Strategy