Once-Weekly Oral Aminopterin for the Treatment of Subjects With Moderate-To-Severe Psoriasis

Inclusion Criteria: 1. Be 18 years of age or older. 2. Have a diagnosis of moderate-to-severe psoriasis for at least 6 months confirmed by a dermatologist, defined here as plaque-type psoriasis affecting a body surface area of \>10% and a PASI of \>10. 3. Agree to avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during the study. 4. Ability to understand and sign written informed consent. 5. Heterosexually active men and women of childbearing potential must use two methods of contraception during the study (20 weeks) and for 90 days after study completion. The two methods of birth control may be used simultaneously in the same subject or simultaneously in both partners. The two birth control methods can be (a) 2 barrier methods or (b) a barrier method plus a hormonal method to prevent pregnancy. Barrier methods include: condom (female or male), copper intrauterine device, sponge, or spermicide. Hormonal Methods include: any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent, including oral, subcutaneous, intrauterine, or intramuscular agents. 6. For pre-menopausal women, a negative pregnancy test, obtained within 1 week prior to first study drug dose and at study visits Week 0, Week 6, Week10, Week 14, and Week 20. If at any visit during the Treatment Phase (see Appendix A) a positive pregnancy test is returned, the subject will be discontinued from any further study drug. 7. Negative serology for human immunodeficiency virus 1 and 2 (HIV1/2), hepatitis B and hepatitis C. 8. The following screening laboratory blood tests must have the following values, or not clinically significant as determined by the PI and Medical Monitor: white blood cells (WBC) within normal limits (WNL); absolute neutrophil count \> lower limit of normal; platelet count WNL; hemoglobin \>10.0 g/dL; aspartate aminotransferase (AST) \< 2.5 x the upper limit of normal. 9. Adequate renal function: creatinine clearance estimated by Cockcroft-Gault formula \>60 ml/min Exclusion Criteria: 1. Known history of hepatitis, HIV infection, interstitial lung disease. 2. Greater than moderate alcohol consumption on a regular basis (moderate consumption for females is 1 drink or 1 glass of wine a day; for males is 2 drinks or 2 glasses of wine a day) and unwilling, or unable, to control consumption during the study period. 3. Prior use of aminopterin (AMT). 4. Use of these biologic treatments in the time frames specified: * Within 9 months of first study drug dose: ustekinumab (Stelara). * Within 12 weeks of first study drug dose: any experimental therapy for psoriasis or rheumatoid arthritis. * Within 8 weeks of first study drug dose: infliximab (Remicade), adalimumab (Humira). * Within 4 weeks of first study drug dose: etanercept (Enbrel). * Other biologic therapies will have discontinuation periods determined by 5x their half-life. 5. Within 90 days prior to Day 0 and at any time while on study, the use of MTX. 6. Within 4 weeks prior to randomization and at any time while on study, use of phototherapy (e.g., ultraviolet B (UVB), narrow band UVB, Goeckerman regimen, Ingram regimen, PUVA), systemic medications (e.g. acitretin, mycophenolate mofetil, tacrolimus/FK506, cyclosporine A, azathioprine, 6-thioguanine, sulfasalazine, hydroxyurea, calcitriol, any systemic immunosuppressants), lithium, or any treatments that could affect psoriasis or sPGA evaluations. Subjects are eligible 4 weeks after the last dose of any of the aforementioned treatments was received. 7. Within 2 weeks prior to randomization and at any time while on study, use of any topical medications or treatments that could affect psoriasis evaluations (e.g., corticosteroids, anthralin, vitamin D3/calcitriol and analogues such calcipotriene and tacalcitol, synthetic retinoids such as tazarotene, coal tar, and keratolytics such as salicylic acid, lactic acid and urea including those contained in over-the-counter medicated shampoos). Subjects are eligible 2 weeks after the last dose of any of the aforementioned treatments was received. Note: Over-the-counter topical steroids will be permitted for use limited to the face, axilla, and/or genitalia, as needed. These topical medications should not be used within approximately 24 hours prior to study visits Day 0 and Day 98. Over-the-counter shampoos for the treatment of psoriasis of the scalp are also permitted. 8. Use of emollients on the morning of the first (Week 0) study visit. 9. Within 2 weeks prior to Study Day 0, or on Study Day 0, or at any time during the study, use of any of the following medications that may result in drug/drug interactions with AMT: trimethoprim with or without sulfamethoxazole; sulfonamides; sulfonylureas; pyrimethamine; tromethamine; salicylates; non-steroidal anti-inflammatory (NSAID) drugs including ibuprofen; dipyridamole; colchicine; probenecid; aminoglycosides; theophylline; phenytoin; and folinic acid (i.e., leucovorin). 10. Known concurrent malignancy except basal or squamous cell skin carcinoma, or cervical carcinoma in situ. 11. Concurrent participation in another clinical trial involving experimental treatment within 30 days of Study Day 0. 12. Current and uncontrolled infection, cardiovascular, renal, pulmonary, hepatic or GI conditions that will interfere with the conduct of the trial or pose a morbid risk. 13. Investigator's opinion that a concurrent disease or condition impairs the subject's ability to complete the trial: includes psychological, familial, sociological, geographical or medical conditions. 14. Breast-feeding.