Anti-CD38 & NAD+ Boost Platelet Counts in Immune Thrombocytopenia: Trial Results

A new study published in Nature Medicine on April 29, 2026, details promising results from a phase 1/2 clinical trial investigating low-dose oral nicotinamide mononucleotide (NMN) as a potential treatment for immune thrombocytopenia (ITP), a chronic autoimmune disorder characterized by low platelet counts. The research builds on previous findings demonstrating that anti-CD38 antibody treatment can rapidly increase platelet counts in patients with refractory ITP, and identifies a key mechanism involving nicotinamide adenine dinucleotide (NAD+) levels and macrophage function.

The phase 1/2 trial enrolled 25 adults with steroid-refractory or steroid-dependent ITP. Participants received 450 mg of NMN twice daily for two weeks. The primary endpoints of the study were safety and tolerability, as well as the proportion of patients achieving a platelet response – defined as a platelet count of 50 x 10⁹ per liter or higher within two weeks, confirmed by two consecutive measurements.

According to the study, NMN was well-tolerated, with no dose-limiting toxicities or treatment-related serious adverse events reported. Mild treatment-related adverse events occurred in 12% of patients, and non-severe infections (grade 1) were observed in 8% of participants. Importantly, immunoglobulin levels remained stable, suggesting that NMN treatment did not compromise humoral immunity. Five patients (20.0%) met the primary platelet-response endpoint.

Mechanism of Action: CD38, NAD+, and Macrophage Polarization

The study sheds light on the mechanism by which anti-CD38 antibody treatment boosts platelet counts. Researchers found that anti-CD38 antibody induces platelet recovery within three days, even after retreatment in patients whose ITP had relapsed. This recovery is linked to a depletion of NAD+ caused by CD38, which drives a shift in macrophage polarization towards an M1-like phenotype. These M1 macrophages exhibit increased expression of Fc gamma receptor I (FcγRI), enhancing their ability to phagocytose (engulf and destroy) opsonized platelets – platelets marked for destruction by autoantibodies.

In laboratory experiments using mice, inhibiting CD38 or supplementing with NMN restored NAD+ levels, reprogrammed macrophages, downregulated FcγRI expression, and prevented thrombocytopenia. NMN treatment did not impair antigen-specific antibody production in an ovalbumin immunization model, indicating that it preserves humoral immune responses.

Implications for ITP Treatment

ITP is an autoimmune disease where the immune system mistakenly attacks and destroys platelets, leading to an increased risk of bleeding. Current treatments often involve broad immunosuppression, which can have significant side effects. The findings from this study suggest a more targeted approach to modulating the immune response in ITP, potentially offering a safer and more effective treatment option.

The researchers note that the observed platelet response rate of 20% in the phase 1/2 trial is encouraging, particularly given the challenging nature of treating patients with steroid-refractory or steroid-dependent ITP. Exploratory analyses revealed that 60% of patients achieved platelet counts greater than 100 x 10⁹ per liter.

Future Research Directions

While these results are promising, further research is needed to confirm the efficacy and optimal dosage of NMN for ITP treatment. Larger, randomized controlled trials are necessary to compare NMN to standard therapies and to identify the patients most likely to benefit from this approach. The study also highlights the potential for targeting the CD38-NAD+ pathway in other autoimmune diseases beyond ITP.

“We previously showed that anti-CD38 antibody can rapidly elevate platelet counts in refractory immune thrombocytopenia (ITP), but the underlying mechanism was unclear.”

Nature Medicine study authors

The study was a single-arm, open-label trial, meaning there was no control group for comparison. This limits the ability to definitively attribute the observed platelet increases to NMN treatment alone. However, the favorable safety profile and mechanistic insights gained from this research provide a strong rationale for continued investigation of NMN as a potential therapeutic strategy for ITP and potentially other autoimmune disorders.