Progressive multiple sclerosis: from pathophysiology to therapeutic strategies

Area of Science:

• Neuroscience
• Immunology
• Neurology

Background:

• Multiple sclerosis (MS) is a chronic central nervous system disease causing demyelination and axonal degeneration.
• Current treatments are effective for relapsing-remitting MS but inadequate for progressive forms, highlighting an unmet clinical need.
• Progressive MS involves complex pathophysiological mechanisms including chronic inflammation, impaired remyelination, and neurodegeneration.

Purpose of the Study:

• To review current understanding of MS progression mechanisms.
• To highlight emerging therapeutic strategies for progressive MS.
• To discuss approaches targeting neuroinflammation, degeneration, and remyelination.

Main Methods:

• Literature review of current research on MS pathophysiology.
• Analysis of disease mechanisms including inflammation, mitochondrial damage, and ion channel alterations.
• Evaluation of emerging therapeutic strategies for progressive MS.

Main Results:

• Chronic inflammation, microglia activation, and T/B cell involvement are key features behind the blood-brain barrier.
• Neuronal mitochondrial damage and energy deficits contribute to axonal degeneration.
• Impaired remyelination and altered ion channel expression exacerbate neurodegeneration.

Conclusions:

• Understanding the complex interplay of inflammation, mitochondrial dysfunction, and impaired repair is crucial for treating progressive MS.
• Emerging therapies focus on modulating neuroinflammation, protecting neurons, and promoting remyelination.
• Targeting these mechanisms offers potential for improved management of progressive multiple sclerosis.