SOD1 Inhibition by Pyrimethamine in Familial Amyotrophic Lateral Sclerosis (ALS)

Inclusion Criteria

• Subjects with definite, probable, or laboratory supported probable ALS will be eligible.
• ALS diagnosed as probable, laboratory supported probable or definite according to the World Federation of Neurology El Escorial criteria [Brooks et al. 2000]
• Age 18 or older
• Capable of providing informed consent and complying with trial procedures
• SOD1 mutation confirmation by study team
• Not taking Riluzole (Rilutek) or on a stable dose for 30 days
• Not taking Coenzyme QR10R or on a stable dose and brand for 30 days
• Absence of exclusion criteria

Exclusion Criteria

• History or evidence of malabsorption syndromes
• Exposure to any experimental agent within 30 days of onset of this protocol
• Women who are pregnant or planning to become pregnant
• Women of childbearing potential not practicing contraception
• Women who are breastfeeding
• Enrollment in another research study within 30 days of or during this trial
• Alcoholism
• Patients taking phenytoin (Dilantin) or other therapy affecting folate levels
• Dementia (MMSE <22)
• Seizure disorder
• Folate deficiency
• Megaloblastic anemia
• Cardiovascular disorder/arrhythmia
• Impaired kidney function, defined as creatinine levels of 2.5 x ULN
• Impaired liver function, defined as AST or ALT of 3 X ULN
• Advanced ALS patients, defined as those with any of the following: forced vital capacity <60% (use of BIPAP is allowed); tracheostomy; or mechanical ventilation
• Use of any of the following medications: cytosine, arabinoside, methotrexate, daunorubicin, sulfonamides, zidovudine, lorazepam, coumadin, sulfamethoxazole, and trimethoprim
• Patients taking Lithium within 30 days of or during this trial
• Incapable of providing informed consent and complying with trial procedures