A Pilot Study of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Generalized Myasthenia Gravis

Twelve patients aged 18-80 with symptomatic generalized autoimmune MG that are not being
treated with medication that suppresses their immune system, other than prednisone, will
enter the study at UIC over a two year period. The study will involve a screening visit and
visits at baseline and at days 5, 15, 30, 45, 60, 90, and 120. The study drug, Leukine
(GM-CFS), is given by injection. Subjects will give themselves one dose of GM-CSF every day
for 10 days. Study visits will include muscle testing, immunologic studies and
quality-of-life studies.

Inclusion Criteria:

- Must be between 18 and 80 years of age

- Established diagnosis of myasthenia based on: the presence of fatigable weakness of
ocular, oropharyngeal, and/or limb muscles AND the presence of abnormal acetylcholine
receptor binding antibodies ≥ 0.4 nmol/l.

- Patients of childbearing potential must agree to use a medically acceptable form of
contraception defined by consistent use of oral contraceptive medications or history
of tubal ligation or men who are in sexual relationship with such women during and
for at least 8 weeks following completion of the study.

- Patient or designee must have the ability to self-inject investigational product

- If thymectomized, the procedure must have been performed at least one year prior to
screening.

- Dose of current anticholinesterase drugs must be constant for 2 weeks prior to
screening.

- If taking prednisone, dose must be stable for ≥4 weeks prior to screening.

Exclusion criteria:

- exclusively ocular MG (MGFA Class I)

- severe respiratory and/ or swallowing muscle weakness (MGFA Class Vb or V)

- presence of thymoma

- Must not have received plasm exchange or IVIG within 4 weeks of screening

- Must not have received immuno-modulating agents within the 4 weeks of screening,
including Azathioprine (Imuran), Cyclosporine (Sandimmune, Neoral), Mycophenolate
mofetil (CellCept), GM-CSF (Filgrastim; Neupogen; pegfilgrastim, sargramostim), or
any other chronic immunosuppressive agent

- History of tuberculosis or evidence of latent tuberculosis (positive PPD skin test or
a chest X-ray with evidence of tuberculosis)

- vital capacity of less than 1.2 liters or on supplemental oxygen therapy.

- severe comorbidities including lung disease, stroke, congestive heart failure of any
severity, myocardial infarction, EKG abnormalities, uncontrolled hypertension -
(sitting systolic BP <80 or > 160 mm Hg or diastolic BP > 100 mm Hg, unstable angina
pectoris, hepatic or renal disease, insulin-dependent diabetes mellitus, history of
cancer (other than in-situ cervical cancer or resected, cutaneous basal cell or
squamous cell carcinoma), open cutaneous ulcers, known hepatitis B surface antigen
(HbsAg) or hepatitis C virus (HCV) positive, or any other concurrent medical
condition, which would make it unsafe for subjects to participate in the trial or
interfere with the interpretation of the results.

- Laboratories values which, at the time of the screening visit or at any time during
the study that in the opinion of the Investigator would preclude participation in the
study including: serum creatinine > 2.5 mg/dL, serum potassium < 3.5 mmol/L or > 5.5
mmol/L, serum aspartate transaminase (AST), alanine transaminase (ALT), or alkaline
phosphatase (ALP)> 3 times the upper limit of normal, platelet count < 100,000/mm3,
WBC count < 3,000 cells/mm3, Hemoglobin, hematocrit, or red blood cell count outside
30% of the upper or lower limits of normal

- Receipt of a live vaccine within 3 months of screening

- participation in another investigational drug study within 90 days of screening.

- known hypersensitivity to GM-CSF or any of its components

- Known HIV-positive status or known history of any other immuno-suppressing disease.

- Any mycobacterial disease.

- Active severe infections within 4 weeks before screening visit, or between the
screening and baseline visits.

- Untreated Lyme disease.

- History of TB or TB exposure, chronic hepatitis B or hepatitis C, SLE, history of
multiple sclerosis, transverse myelitis, optic neuritis or epilepsy.

- History of recent alcohol or substance abuse (< 1 year)

- Pregnant or lactating females

- History of non-compliance with other therapies

- abnormal mental status sufficient to exclude informed consent

- History of any opportunistic infection - to include but not limited to Pneumocystis
carinii, aspergillosis, histoplasmosis, or atypical mycobacterium

- History of Sickle cell disease.