A combination therapy of low-dose methylprednisolone and interferon (IFN)-beta-secreting stem cells is effective in a mouse model of multiple sclerosis (MS), a new Korean study suggests.
Doctors often prescribe methylprednisolone, a corticosteroid used to suppress the immune system and decrease inflammation, to MS patients. However, high doses over a long period are inconvenient and costly. They may cause side effects including weight gain and decreased resistance to infection, as well as hyperglycemia (high levels of glucose in the blood).
In a mouse model of MS known as the experimental autoimmune encephalomyelitis (EAE) mouse, methylprednisolone suppressed disease activity and progression. However, combining low-dose methylprednisolone with other drugs also reduced clinical severity in mice, suggesting that new formulations may decrease MS severity while avoiding the side effects of high-dose methylprednisolone.
IFN-beta, an approved therapy for MS, has potent anti-inflammatory and immunomodulatory effects. Yet its short half-life — the period of time over which the concentration of the drug in the body falls by half — hampers its therapeutic efficacy. IFN-beta’s inability to cross the blood-brain barrier and reach the central nervous system is also a disadvantage.
The research team at Seoul’s Catholic University of Korea previously showed that IFN-beta-secreting mesenchymal stem cells (MSCs-IFN-beta) derived from human bone marrow reduce the severity of MS and in EAE mice. Specifically, stem-cell treatment decreased inflammatory cell infiltration, mitigated the loss of myelin and promoted anti-inflammatory effects.
MS symptoms and pathological mechanisms are complex. For this reason, combination therapies targeting multiple disease aspects could provide significant therapeutic benefit.
In the latest study, investigators assessed whether combining low-dose methylprednisolone and MSCs-IFNβ could offer more therapeutic benefits to EAE mice than either therapy alone.
Results showed that the combo treatment decreased disease severity and inflammatory cell infiltration, and helped repair the myelin sheath. In addition, the combo treatment reduced disruption of the blood-brain barrier as well as reactivation and death of T-cells, a type of immune cell involved in MS development.
Overall, the study shows “for the first time that a combined treatment consisting of MP [methylprednisolone ] and MSCs-IFN[-beta] has enhanced therapeutic efficacy compared with each treatment individually. These results provide invaluable insight into the potential of combined treatments with standard MS drugs and may offer new therapeutic options for treating patients with MS.”