New research shows the potential of melatonin to reduce corticosteroid dosage in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease of unknown origin, considered the leading cause of non-traumatic disability in young people, affecting approximately 50,000 people in Spain. It is characterized by the infiltration of encephalitogenic cells into the central nervous system (CNS), causing the appearance of multifocal areas of demyelination and ultimately leading to neurodegeneration. The most common form of the disease, relapsing-remitting multiple sclerosis (RR-MS), is characterized by acute inflammatory episodes that lead to varying degrees of disability followed by partial or complete recovery.

In this sense, first-line treatment for relapsed RR-MS consists of administering high doses of glucocorticoidsespecially methylprednisolone, for three to five days in a row. However, this approach has limitations. Methylprednisolone, although effective, can cause serious side effects, including osteoporosis, hypertension, and sleep disturbances. In addition, some patients develop hypersensitivity to corticosteroids, further complicating their treatment. In fact, one study found that long-term use of corticosteroids may contribute to bone fragility and fracture risk in patients with multiple sclerosis, especially those who are chronically treated.

A recent study by the Molecular Neuroimmunoendocrinology Research Group of the Institute of Biomedicine of Seville (IBiS) and the University of Seville has highlighted the potential of melatonin as an adjunctive treatment in relapsing-remitting multiple sclerosis (MS). . The results, published in the scientific journal Autoimmunity, show that combined use of melatonin and corticosteroids (methylprednisolone) It provided protection in 90 percent of animals studied, achieving significant reductions in neuroinflammation. In addition, this combination can significantly reduce the required dose of corticosteroids to obtain the desired therapeutic effect.

Reduce neuroinflammation

A study by the Molecular Neuroimmunoendocrinology Group led by Professor Antonio Carrillo Vico found that co-administration of melatonin and methylprednisolone protected 90 percent of the animals studied from developing symptoms of multiple sclerosis. In addition, co-treatment with melatonin allowed reduce the dose of methylprednisolone to four timeswhich represents a significant reduction in the side effects associated with long-term corticosteroid use. Melatonin is also known for its safety profile and low risk of side effects, making it an attractive candidate for use in combination with existing treatments.

“This finding is significant because we not only confirmed the effectiveness of melatonin in enhancing the effect of corticosteroids, but also observed that melatonin itself can improve the resolution of disease flare and enhance the effect of corticosteroids.” in subsequent relapse,” Carrillo said.

Melatonin reduces the entry of pathogenic immune cells such as CD4+ T cells, B cells, macrophages and dendritic cells into the central nervous system, helping to limit neuroinflammation. In addition, melatonin treatment stimulates the production of anti-inflammatory markerswhich contributes to less destruction of myelin and, therefore, better protection of nerve fibers.

The results of this preclinical study, together with the team’s previous research, laid the foundation for the development of a human clinical trial called MELATOMES-1. This study, coordinated by the IBiS team in collaboration with the Virgen del Rocío University Hospital (HUVR) and the Virgen Macarena University Hospital (HUVM) in Seville, aims to evaluate the use of melatonin in patients with primary progressive multiple sclerosis (EM-PP). ), the most aggressive form of the disease, for which only one drug is currently approved in Spain.

“Melatonin’s potential to reduce inflammation and corticosteroid dosage in multiple sclerosis could mean a significant improvement in patients’ quality of life,” Carrillo said. The MELATOMS-1 study is a multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the safety and effectiveness of melatonin in patients with primary progressive multiple sclerosis (EM-PP) who are already receiving treatment with ocrelizumab. This approach aims to determine whether melatonin can act as an adjunctive treatment to improve clinical outcomes and slow disease progression in this highly aggressive form of multiple sclerosis.

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