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Myelin repairLaboratory or animal researchMixed findings

Mouse and brain-slice experiments before human testing

MMP-9 loss changed microglial responses but had little effect on remyelination in mice

Published by MyelinWatch:

Organisation
Acta Neuropathologica Communications

What happened

A study tested whether deleting matrix metalloprotease-9 (MMP-9) affects myelin injury and repair. In isolated brain slices, deficiency impaired repair through microglia/macrophage-related mechanisms. In the cuprizone mouse model, deficiency increased activated microglia/macrophages but had minimal impact on demyelination or remyelination. Proteomic and cell analyses pointed to altered inflammatory responses, not a demonstrated repair therapy.

What this means for people with MS

This helps map a complex repair-related pathway and cautions against assuming that suppressing MMP-9 will restore myelin. Mouse and slice findings cannot establish a treatment effect, safety, or benefit for people with MS. No approved clinical treatment has been shown to reliably restore myelin in MS.

What kind of evidence exists?
Cuprizone-treated mice and ex-vivo brain slices comparing MMP-9 deficiency with controls
How reliable is this source?
Full peer-reviewed primary paper reviewed; complementary ex-vivo and mouse models produced different repair effects. No human treatment study.
Source: Acta Neuropathologica Communications — peer-reviewed primary article ↗
Research event/source date
Published by MyelinWatch
Last substantive MyelinWatch update

Related substantive developments

Research event/source date:
Myelin repairResults from peopleNo reported conclusion on effect

Published longitudinal imaging cohort study in people

MRI study follows a myelin-sensitive signal in MS lesions over about one year

Organisation: Second Hospital & Clinical Medical School, Lanzhou University · China

Researchers at the Second Hospital of Lanzhou University, China, used an MRI technique called APART-QSM, which separates a myelin-sensitive (diamagnetic) signal from an iron-sensitive one. At the first scan, white matter lesions had a lower myelin-sensitive signal than the corresponding normal-appearing white matter. In the 101 people with multiple sclerosis who had a second scan after a median of about one year, the myelin-sensitive signal in lesions increased. Larger increases were associated with female sex, ofatumumab treatment, relapsing-remitting MS and improvement in EDSS disability scores, and they were smaller with longer disease duration.

Published by MyelinWatch:

What this means for people with MS

The work tests whether this MRI method could track changes linked to remyelination. It does not show that myelin was restored, that ofatumumab repairs myelin, or that the signal explains changes in disability: this was an observational cohort with no randomised comparison of treatments, and about 30% of the people with MS had no follow-up scan. There is still no established approved treatment in clinical practice proven to reliably restore myelin in MS. It does not support a change to an individual treatment.

Read the update →Source: Journal of Magnetic Resonance Imaging (Wiley) — peer-reviewed primary article ↗
Research event/source date:
Myelin repairLaboratory or animal researchLess myelin damage and inflammation in mouse models; not clinical benefit

Mouse experiments; not tested in people

Mouse study links chronic demyelination to a dysfunctional microglial state

Organisation: Technical University of Munich and German Center for Neurodegenerative Diseases (DZNE) · Germany

Researchers at the Technical University of Munich and the German Center for Neurodegenerative Diseases (DZNE) compared mouse models of acute and chronic myelin loss. With chronic demyelination, microglia, the brain's immune cells, entered a distinct state with ongoing inflammation, fats trapped inside their lysosomes and fewer lipid droplets, together with higher cholesterol production and lower cholesterol export. A desmosterol-like compound (DMHCA) reversed this state, reduced inflammatory signalling and myelin damage, and improved movement in a mouse model of the inherited myelin disorder Pelizaeus–Merzbacher disease. In experimental autoimmune encephalomyelitis (EAE), a mouse model used to study MS, DMHCA lessened disease severity and reduced lesions. In post-mortem tissue from chronic active MS lesions of 3 people, about 75% of phagocytic immune cells (CD68+) carried a marker of this inflammatory state (CCL4), compared with about 13% in white matter from people without MS.

Published by MyelinWatch:

What this means for people with MS

The study points to a possible research target for chronic myelin damage, including in MS. The compound was given only to mice, EAE mice do not reproduce all features of MS, and the human finding is a small descriptive tissue observation, so the work cannot show that the compound would be safe or useful for people with multiple sclerosis. There is no established approved treatment in clinical practice proven to reliably restore myelin in MS. It does not support a change to an individual treatment.

Read the update →Source: Nature Neuroscience — peer-reviewed primary article ↗
Research event/source date:
Myelin repairLaboratory or animal researchMore maturing myelin-forming cells in aged rodents; not clinical benefit

Rat cell and mouse experiments; not tested in people

Rodent study: restoring BCL11A helped aged myelin precursor cells mature

Organisation: Altos Labs-Cambridge Institute of Science and University of Cambridge · United Kingdom

Researchers at Altos Labs-Cambridge Institute of Science and the University of Cambridge, UK, studied why oligodendrocyte progenitor cells, the precursor cells that can form new myelin, mature less well with age. Using a new computational method (gSWITCH) on gene-activity data from young and aged rats, they found several regulatory genes with lower activity in aged precursor cells and highlighted one, BCL11A. Blocking BCL11A reduced the maturation of these precursor cells into myelin-forming cells (oligodendrocytes). Adding BCL11A to precursor cells from aged rats in the lab increased the number of oligodendrocytes by about 54% without changing cell division. In 18-month-old mice, raising BCL11A in these cells with a viral gene vector before a chemically induced spinal cord lesion led to more maturing oligodendrocytes in the lesion 14 days later; the authors report no difference in lesion size.

Published by MyelinWatch:

What this means for people with MS

The study points to a gene that may help explain why myelin repair slows with age, a question relevant to MS. It did not test a treatment: BCL11A was raised by gene delivery in rodents, the lesion was chemically induced rather than an MS model, and the study counted maturing cells rather than measuring restored myelin or recovery of function. It cannot show that this approach would be safe or useful for people with multiple sclerosis. There is no established approved treatment in clinical practice proven to reliably restore myelin in MS. It does not support a change to an individual treatment.

Read the update →Source: eLife — peer-reviewed primary article ↗