In Amyotrophic Lateral Sclerosis (ALS), the reduction of regulatory T-lymphocyte (Treg) numbers and suppressive function correlates with rapid disease progression. The investigator completed a phase 1 study of infusions of expanded autologous Tregs in combination with subcutaneous IL-2 injections in ALS patients, which showed enhancement of Treg numbers and suppressive function in vivo. The enhanced Treg suppressive function correlated strongly with slowing and stabilization of disease progression. Drugs that enhance endogenous Treg numbers and suppressive function may also stabilize disease in ALS. This phase 1 study aims to determine whether the combination therapy of subcutaneous IL-2 and abatacept (Orencia®) is safe and well-tolerated in 6 patients with ALS, and whether the therapy enhances Treg numbers and suppressive function in vivo.

Inclusion Criteria:

Patients will be eligible for initial enrollment on this study if they meet the following criteria at the time of screening:

1. Provided informed consent and authorized use of protected health information (PHI) in accordance with national and local patient privacy regulations.
2. ALS meeting El Escorial criteria for possible, probable, lab-supported probable, or definite ALS.
3. At least 18 years old.
4. Total bilirubin less than or equal to 1.5 mg/dL
5. Alanine aminotransferase level (ALT) less than or equal to five times normal, albumin greater than or equal to 3.0 gm/dL
6. Serum creatinine less than 1.5 mg/dL
7. Capable of complying with all study procedures, including the study drug delivery procedure, in the Investigator's opinion.
8. A family member or caretaker who is expected to be consistently available to administer both study drugs of abatacept and IL-2 if the participant is unable to do so.
9. On a stable regimen of riluzole for at least 30 days at the time of screening. If not on riluzole at the time of study entry, willing to refrain from initiation of the agent for the duration of the trial.
10. Patients on edaravone willing to refrain from taking edaravone on the same day as they will receive the abatacept injection for the duration of the trial. If not on edaravone at the time of study entry, willing to refrain from initiation of the agent for the duration of the trial.
11. Forced vital capacity (FVC) ≥50% of predicted capacity for age, height, and sex at screening, or receiving treatment with noninvasive ventilation if FVC < 50% of predicted for age, height, and sex at screening.

Exclusion Criteria:

Patients will be ineligible to participate if any of the following are true at the time of screening:

1. Serious, active bacterial, fungal, or viral infection, active or latent tuberculosis.
2. Tracheostomy.
3. Severe cardiac dysfunction defined as left ventricular ejection fraction <40% if an echocardiogram is medically indicated to clarify ongoing symptoms or EKG findings.; a history of non-controlled cardiac arrhythmias; history of cardiac tamponade; Unstable angina or MI in the last 3 months.
4. Hypersensitivity or allergy to IL-2 or abatacept.
5. History of bowel ischemia/perforation, or GI bleeding requiring surgery.
6. History of resistant seizures, history of coma or toxic psychosis lasting >48 hours.
7. Platelets <100,000/mm3; hematocrit <30%.
8. History of cancer in the past 5 years (except cutaneous Basal cell carcinoma or squamous cell carcinoma).
9. Hx of immunomodulation therapy including IL-2 or abatacept administration in the past 90 days.
10. Treatment with another investigational drug, biological agent, or device within 30 days or 5 half-lives of screening, whichever is longer.
11. If female, breastfeeding, known to be pregnant, planning to become pregnant during the study, or unwilling to use effective contraception for the duration of the trial and for 90 days after treatment.
12. If male of reproductive capacity, unwilling to use effective contraception for the duration of the trial and for 90 days after treatment