Evaluation of Donor-Derived B Cell Infusions in Patients With Amyotrophic Lateral Sclerosis (ALS)

This study is testing whether giving people with ALS specially matched immune cells called B cells from a related donor is safe. Up to 10 participants will each receive two B cell infusions at least 60 days apart. The main goals are to watch closely for side effects, see whether the participant's immune system rejects the donor cells, and determine whether this treatment should be studied further in people with ALS. The first three participants will receive the infusions in the hospital with extra safety spacing between participants; if those infusions appear safe, the remaining participants may receive them in an outpatient setting.

Inclusion Criteria: 1. Confirmed diagnosis of ALS that meets the revised El Escorial criteria for probable lab-supported, probable, or definite ALS. 2. Age 18-70 years. 3. Vital capacity of \>65%. 4. ALSFRS-R score of \>30. 5. Absence of clinically important abnormalities on screening labs, including but not limited to ALT/AST \< 3x ULN, Bilirubin \ 6 months). 11. Other active autoimmune disease except psoriasis or hypothyroidism. 12. Active malignancy (excluding skin cancer other than melanoma) within 5 years. 13. History of any of the following: cardiac insufficiency (defined as New York Heart Association III/IV), unstable ischemic heart disease, uncontrolled cardiac arrhythmias, or uncontrolled hypertension (defined as systolic blood pressure \>170 mmHg or diastolic blood pressure \>110 mmHg). 14. Unstable cardiac, renal, hepatic, endocrine, pulmonary or hematologic disease, at the discretion of the PI. 15. Anything that, in the opinion of the PI, would place the participant at increased risk or preclude the participant's full compliance with or the completion of the study. 16. Participant unwilling to practice contraception for the duration of the study. Men and women of childbearing potential (WOCBP) should use an approved method of birth control and agree to continue to use this method for the duration of the study. Acceptable methods of contraception include abstinence, female participants/partner's use of hormonal contraceptive (oral, implanted, or injected) in conjunction with a barrier method (WOCBP only) (e.g., diaphragm, cervical cap, male condom, and female condom and spermicidal foam, sponges, and film), female participant's/partner's use of an intrauterine device (IUD), or if the female participant/partner is surgically sterile (e.g., bilateral tubal ligation, hysterectomy) or two years postmenopausal at time of screening. All male participants/partners (excluding men who have been sterilized) must agree to consistently and correctly use a condom for duration of the study. In addition, participants may not donate sperm for the duration of the study. 17. Participation in another interventional trial or use of an experimental ALS product with an ongoing clinical development program in an expanded access program, compassionate use program or through practitioner prescription. Over the counter medications are acceptable, as are standard of care ALS medications.