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 \<1.5x ULN (unless there is documented history of Gilbert's disease), serum Cr \< 1.5x ULN, WBC \> 3.5, HCT \>33, Plts \> 120.
6. Negative tests for HIV, HepB sAg, HCV.
7. Available potential donor who must be a haploidentical match to the recipient and agree to be the B cell donor for this study.
* Note: Participants are eligible if they are taking any, all, or none of the following: riluzole, edaravone, and/or high-dose methylcobalamine; and the start date of these medications are at least 30 days prior to the baseline visit.
Exclusion Criteria:
1. Unable or unwilling to comply with protocol requirements.
2. Known current or history of recurrent bacterial, viral, fungal, mycobacterial, or other opportunistic infection.
3. Use of tofersen (Qalsody).
4. Use of Rituximab (Rituxan), Ocrelizumab (Ocrevus), Ofatumumab (Kesimpta, Arzerra), Epratuzumab (LymphoCide), Belimumab (Benlysta), MEDI-551, or other anti-CD20, anti-CD19, or anti-CD22 antibodies.
5. Use of Atacicpet or other BlyS or APRIL inhibitors.
6. Use of Chimeric antigen-receptor T cells targeting CD19 or CD20, including tisagenlecleucel (Kymriah), Aaxicabtagene ciloleucel (Yescarta), brexucabtagene autoleucel (Tecartus), and lisocabtagene maraleucel (Breyanzi).
7. Additional active neurological disease that could confound the participant's ALS symptoms.
8. Major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening.
9. Immunization with live-attenuated vaccines within 4 weeks of screening. Study participant must agree to forgo live-attenuated vaccines throughout the study.
10. Chronic immunosuppression (any chronic immunosuppressive immunotherapy including daily oral steroid use \> 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.
