Medications and Therapies

Drugs acting on or through oligodendrocytes: approved MS therapies, remyelination candidates, and investigational agents.

2026-09-09 · New England Journal of Medicine
Hauser et al.: Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis

Anti-CD20 B-cell depletion reduces relapse rate and new lesions in relapsing MS. Oligodendrocyte protection is indirect, by removing the immune attack.

2026-09-09 · New England Journal of Medicine
Montalban et al.: Ocrelizumab versus placebo in primary progressive multiple sclerosis

The trial behind the first approval for primary progressive MS, a form with no previous disease-modifying option.

2026-09-09 · New England Journal of Medicine
Polman et al.: A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis

Anti-VLA-4 blocks lymphocyte entry to the CNS. Carries PML risk, which is JC virus replicating in oligodendrocytes themselves.

2026-09-09 · Lancet
Green et al.: Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD)

An antimuscarinic antihistamine repurposed as a differentiation promoter. In this crossover trial it shortened visual evoked potential latency in chronic optic neuropathy, the first remyelination signal from a drug in humans.

2026-09-09 · Lancet
Kappos et al.: Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND)

S1P receptor modulator approved for secondary progressive MS. S1P5 is expressed on oligodendrocytes, so a direct effect is plausible alongside the immune one.

2026-09-09 · Multiple Sclerosis Journal
Tourbah et al.: MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis

High-dose biotin as a cofactor for the carboxylases in myelin fatty acid synthesis. Later phase III work did not confirm the benefit; not approved.

2026-09-09 · Nature
Deshmukh et al.: A regenerative approach to the treatment of multiple sclerosis

High-throughput screen identifying benztropine and other antimuscarinics as OPC differentiation promoters. The origin of the clemastine hypothesis.

2026-09-09 · Nature Neuroscience
Huang et al.: Retinoid X receptor gamma signaling accelerates CNS remyelination

RXR gamma is required for OPC differentiation; agonists accelerate remyelination in aged rodents. The retinoid pathway as a repair target.

2026-09-09 · Nature Neuroscience
Fancy et al.: Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination

Stabilising Axin2 dampens Wnt signalling in OPCs and accelerates their maturation, linking a developmental pathway to a repair target.

2026-09-10 · PNAS
Nanou et al.: Fibronectin inhibition restores myelination in endothelial TNFR2-dependent nonremitting experimental autoimmune encephalomyelitis

Mouse, preclinical. Fibronectin piling up in lesions traps OPCs short of repair; inhibiting it systemically restored remyelination and clinical remission.

2026-09-10 · Pharmacological Research
Raffaele et al.: Selective targeting of the oligodendroglial GPR17 receptor improves myelin integrity and motor function in female SOD1G93A mice

Mouse ALS model. A brain-penetrant GPR17 agonist restored oligodendrocyte maturation, extended survival and improved motor function in females, with no benefit in males.