The goal of treating rheumatoid arthritis has, in recent years, been a complete remission, i.e., cessation of disease activity. Neurologists seem much more cautious and risk-averse in treating multiple sclerosis.
Dr Gavin Giovannoni has been a forceful advocate of a different approach. He outlined this strategy at the 2016 AAN Annual Meeting.
His goal is to treat simultaneously all the pathogenic processes that underpin progressive MS. These strategies include:
- Anti-inflammatory therapies, which deal with both adaptive and innate immune responses.
- Neuroprotective therapies.
- Remyelination strategies.
Controlling the initial autoimmune-driven inflammatory component is key. Thereafter, neuroprotection should be sought for all stages of the disease. Lastly, remyelination medications fully improve recovery from relapses. They are less likely to lead to regaining lost function.
Further, he believes that aggressive treatment early in the disease is best. He views stem cell therapy as most effective and Lemtrada next for patients with poor prognostic factors and who have demonstrated an early aggressive course.
Neuroprotective therapies include sodium channel blockers, such as phenytoin, lamotrigine, riluzole, and oxcarbazepine; ion channel-1 blockers, such as amiloride; SSRIs, such as fluoxetine; phosphodiesterase inhibitors, such as ibudilast; microglial inhibitors, such as laquinimod and minocycline; and drugs that improve mitochondrial function, such as biotin and idebenone.
Regarding remyelination, there are 6 compounds in clinical trials. A monoclonal antibody to LINGO-1 is furthest along. Next is a retinoid X receptor agonist, then a muscarinic antagonist (benztropine). Also in trials is an antihistamine H3 antagonist, developed by GSK and termed clemastine; an anti-SEMA4D (VX15); and lastly biotin.
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