| First Author | Sîrbulescu RF | Year | 2024 |
| Journal | FASEB J | Volume | 38 |
| Issue | 13 | Pages | e23796 |
| PubMed ID | 38967302 | Mgi Jnum | J:357723 |
| Mgi Id | MGI:7763752 | Doi | 10.1096/fj.202302659R |
| Citation | Sirbulescu RF, et al. (2024) Allogeneic B cell immunomodulatory therapy in amyotrophic lateral sclerosis. FASEB J 38(13):e23796 |
| abstractText | Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease. Immune system dysregulation plays an essential role in ALS onset and progression. Our preclinical studies have shown that the administration of exogenous allogeneic B cells improves outcomes in murine models of skin and brain injury through a process termed pligodraxis, in which B cells adopt an immunoregulatory and neuroprotective phenotype in an injured environment. Here, we investigated the effects of B-cell therapy in the SOD1(G93A) mouse preclinical model of ALS and in a person living with ALS. Purified splenic mature naive B cells from haploidentical donor mice were administered intravenously in SOD1(G93A) mice for a total of 10 weekly doses. For the clinical study in a person with advanced ALS, IgA gammopathy of unclear significance, and B lymphopenia, CD19(+) B cells were positively selected from a healthy haploidentical donor and infused intravenously twice, at a 60-day interval. Repeated intravenous B-cell administration was safe and significantly delayed disease onset, extended survival, reduced cellular apoptosis, and decreased astrogliosis in SOD1(G93A) mice. Repeated B-cell infusion in a person with ALS was safe and did not appear to generate a clinically evident inflammatory response. An improvement of 5 points on the ALSFRS-R scale was observed after the first infusion. Levels of inflammatory markers showed persistent reduction post-infusion. This represents a first demonstration of the efficacy of haploidentical B-cell infusion in the SOD1(G93A) mouse and the safety and feasibility of using purified haploidentical B lymphocytes as a cell-based therapeutic strategy for a person with ALS. |
