Evidence suggestive of partial lesion remyelination after alemtuzumab therapy has been found by Australian researchers using a unique visual neuronal pathway model.
A team at the Sydney Neuroimaging Analysis Centre, and the Australia Brain and Mind Centre, University of Sydney, used measurements of visual evoked potential (VEP) latency as a surrogate marker of myelin integrity/recovery in the optic nerve to investigate the effects of the anti-CD52 monoclonal antibody which is known to have a sustained anti-inflammatory effect in people with relapsing MS.
In a prospective study they monitored clinical, multifocal visual evoked potential (mfVEP) and MRI outcomes in 30 patients starting alemtuzumab for relapsing MS, and a control group of 20 healthy individuals, over 24 months.
They found that over the study period there was a significant shortening of mfVEP latency of 1.21 ms, which was still evident after adjusting for age, gender, disease duration and change in lesion volume.
In the control group there was a small but nonsignificant increase (0.72ms) in mean mfVEP latency over the course of the study.
In the patients with MS, analysis of chronic OR T2 lesions showed a significant increase in normalised fractional anisotropy and axial diffusivity from baseline to 24 months (both p<0.01).
Visual acuity (Mean Mars letter contrast sensitivity) was improved at 24 months compared to baseline, and was driven by an early improvement, in both patients and in the healthy control group.
The researchers said the modest improvements in VEP latency potentially reflected remyelination of MS lesions in the visual pathway as a results of alemtuzumab treatment.
They said similar modest but potential pro-remyelinating effects had been seen with drugs such as clemastine and opicinumab in patients with relapsing MS.
It was notable that inn preclinical studies these agents had also shown effects on oligodendrocyte precursor cells and produced robust remyelination in the absence of immunomodulation.
However, since alemtuzumab causes immune cell depletion it was not possible to separate its strong anti-inflammatory effects from a potentially independent, pro-reparative mechanism of action in MS, the authors said.
Nevertheless, they noted the study showed a small increase in global retinal nerve fibre layer over two years in patients with MS over two years, possible evidence of axonal stability in the optic nerve, “which in turn could potentially reflect remyelination with secondary neuroprotection.”
“Although limited by its observational nature, relatively small size and lack of a true control group, our study nevertheless provides insights into the mechanisms of sustained clinical and MRI improvements following therapy with alemtuzumab and a framework for future remyelination trials,” they concluded.
The findings are published in the Journal of Neurology Neurosurgery and Psychiatry.