Next wave of DMTs

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frodo
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Next wave of DMTs

Post by frodo »

These are the new expected DMT in the horizon:

The Future of Progressive Multiple Sclerosis Therapies

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182248/

Lipoic acid (LA), also known as α-lipoic acid and thiotic acid. It has antioxidant (AO) properties including direct radical scavenging, regeneration of glutathione, and upregulation of AO enzymes.

Simvastatin also targets alternative pathophysiology in SPMS. It has anti-inflammatory effects, improves vascular function, and promotes neuroprotection by reducing excitotoxicity. A phase 2 RCT demonstrated a reduction in whole brain atrophy in SPMS (n = 140), and a phase 3 trial is underway.

Lithium and riluzole promote neuroprotection by reducing excitotoxicity. Three neuroprotective agents, riluzole (reduces glutamate excitotoxicity), fluoxetine (stimulates glycogenolysis and improves mitochondrial energy production), and amiloride (an acid-sensing ion channel blocker that opens in response to inflammation) were tested in a phase 2b multi-arm, multi-site parallel group RCT in SPMS (n = 445). The study failed to yield differences from placebo for any agent in reduction of brain volume loss.29 A prior study of lamotrigine, a sodium channel blocker, also failed to find changes in brain volume loss.30 These studies highlight the large sample sizes and/or long study durations needed to test agents using brain atrophy as primary outcome. In the future, precise surrogate markers of neuroprotection will be a great need for earlier phase trials. These results also suggest that targeting > 1 MOA may be necessary to treat SPMS effectively.

High dose biotin (about 10,000× usual dose) may promote myelin repair as a cofactor for fatty acid synthesis and support mitochondrial oxidative phosphorylation. While a RCT yielded a greater proportion of participants with either PPMS or SPMS with improvement in disability than placebo at 12 months, an open label trial suggested otherwise indicating a need for a more definitive trial.

Anti-LINGO-1 (opicinumab) is a monoclonal antibody that targets LINGO, a potent negative regulator of oligodendrocyte differentiation and myelination. Although this agent failed in a phase 2 trial in relapsing MS, and is thus unlikely to be tested in progressive forms, the innovative approach to stimulating oligodendrocytes is ongoing. One such effort is to use thyroid hormone, crucial to myelin formation during development, as a repair agent in MS
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