Monday, 5 October 2015

Remyelination saves nerves

Wootla B, Denic A, Watzlawik JO, Warrington AE, Rodriguez M.
Antibody-Mediated Oligodendrocyte Remyelination Promotes Axon Health in Progressive Demyelinating Disease. Mol Neurobiol. 2015 Sep. [Epub ahead of print]

Demyelination underlies early neurological symptoms in multiple sclerosis (MS); however, axonal damage is considered critical for permanent chronic deficits. The precise mechanisms by which axonal injury occurs in MS are unclear; one hypothesis is the absence or failure of remyelination, suggesting that promoting remyelination may protect axons from death. This report provides direct evidence that promoting oligodendrocyte remyelination protects axons and maintains transport function. Persistent Theiler's virus infection of Swiss Jim Lambert (SJL)/J mice was used as a model of MS to assess the effects of remyelination on axonal injury following demyelination in the spinal cord. Remyelination was induced using an oligodendrocyte/myelin-specific recombinant human monoclonal IgM, rHIgM22. The antibody is endowed with strong anti-apoptotic and pro-proliferative effects on oligodendrocyte progenitor cells. 

We used 1H-magnetic resonance spectroscopy (MRS) at the brainstem to measure N-acetyl-aspartate (NAA) as a surrogate of neuronal health and spinal cord integrity. We found increased brainstem NAA concentrations at 5 weeks post-treatment with rHIgM22, which remained stable out to 10 weeks. Detailed spinal cord morphology studies revealed enhanced remyelination in the rHIgM22-treated group but not in the isotype control antibody- or saline-treated groups. Importantly, we found rHIgM22-mediated remyelination protected small- and medium-caliber mid-thoracic spinal cord axons from damage despite similar demyelination and inflammation across all experimental groups. The most direct confirmation of remyelination-mediated protection of descending neurons was an improvement in retrograde transport. Treatment with rHIgM22 significantly increased the number of retrograde-labeled neurons in the brainstem, indicating that preserved axons are functionally competent. This is direct validation that remyelination preserves spinal cord axons and protects functional axon integrity.

Remyelination saves nerves

8 comments:

  1. This study used TMV as a model to show remyelination. Will rHIgM22 cross the BBB in MSers?

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    1. There is a presentation at ectrims2015about phase I and they mention it does get in, but to what extent I will have to see

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    2. Dear MD,

      QQ: why do we consider crossing the BBB rather than intrathecal infusion?

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    3. Good question intrathecal/ventricular would be a better option. I'll see what the phase I trial says and report back

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  2. It works like that in mice, but what about clams or screaming pihas?

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  3. Perhaps this is already a step further, and realistic, than anti-Lingo1 can do ... Studies with rHIgM22 are at what stage?

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    1. If we look at ECTRIMS we can see that rHigM22 is finished phase I and ant-LINGO-1 is phase II with positive results

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