Low-dose oral nicotinamide mononucleotide for immune thrombocytopenia: a phase 1/2 trial

Autoimmunity remains challenging to treat without broad immunosuppression. We previously showed that anti-CD38 antibody can rapidly elevate platelet counts in refractory immune thrombocytopenia (ITP), but the underlying mechanism was unclear.

Here we report that anti-CD38 antibody induces platelet recovery within 3 days, including after retreatment in relapsed cases. Mechanistically, CD38-mediated nicotinamide adenine dinucleotide (NAD + ) depletion drives M1-like macrophage polarization with increased Fc gamma receptor I (FcγRI) expression, thereby promoting macrophage phagocytosis of opsonized platelets.

In mice, CD38 inhibition or nicotinamide mononucleotide (NMN) supplementation restores NAD + , reprograms macrophages, downregulates FcγRI and prevents thrombocytopenia. In an ovalbumin immunization model, NMN treatment does not impair antigen-specific antibody production, supporting preservation of humoral responses.

Based on these findings, we conducted a single-arm, open-label phase 1/2 trial of low-dose oral NMN (450 mg twice daily for 2 weeks) in adults with steroid-refractory or steroid-dependent ITP.