Intranasal delivery of M2 macrophage-derived soluble products reduces neuropsychological deficit in patients with cerebrovascular disease: a pilot study

Abstract

Objective:We assessed the safety and clinical effectiveness of intranasal therapy with M2 macrophage-derived soluble products (M2-SPs) for treating patients with cerebrovascular disease (CVD).Materials and methods:The protocol of the study was registered at www.ClinicalTrails.gov (NCT02957123). The study group comprised 30 patients with chronic CVD. Neurological status was examined before therapy and at 1- and 6-month follow–up. Concentrations of 32 cytokines in the blood serum were evaluated before and 1 month after therapy onset. Neurological assessment was conducted with the following scales: Subjective Assessment of Clinical (neurological) Symptoms (SACS), Hospital Anxiety and Depression Scale (HADS), Functional Mobility Assessment in Eldery Patients (FMA), and Montreal Cognitive Assessment (MoCa).Results:M2-SPs treatment (once daily for 28~30 days) was found to be safe and well tolerated. Neuropsychological improvements showed the amelioration of neurological symptoms, reduction in anxiety and depression levels, improvement in balance and gait ability as well as cognitive functions. Clinical effects could be detected at the end of treatment course and was stable during 6-month follow-up. Blood serum cytokine evaluation demonstrated diminished baseline levels of many cytokines including those with neurotrophic activity (brain-derived neurotrophic factor, BDNF; hepatocyte growth factor, HGF; migration inhibitory factor, MIF). Upon treatment, most pronounced clinical responses were observed in patients with most severe cytokine deficiency and post-therapy normalization of MIF and HGF levels.Conclusion:Intranasal therapy with M2-SPs is safe and according to preliminary data reduces neuropsychological deficit in patients with chronic CVD. The positive effect of M2-SPs treatment seems to be HGF- and MIF-dependent.

Keywords

• chronic cerebrovascular disease
• intranasal therapy
• m2-macrophages
• cytokines
• neurological improvement