Demicheva E, Cui YF, Bardwell P, Barghorn S, Kron M, Meyer AH, Schmidt M, Gerlach B, Leddy M, Barlow E, O’Connor E, Choi CH, Huang L, Veldman GM, Rus H, Shabanzadeh AP, Tassew NG, Monnier PP, Müller T, Calabresi PA, Schoemaker H, Mueller BK. Cell Rep. 2015 pii: S2211-1247(15)00206-5. doi: 10.1016/j.celrep.2015.02.048. [Epub ahead of print]
Repulsive guidance molecule A (RGMa) is a potent inhibitor of neuronal regeneration and a regulator of cell death, and it plays a role in multiple sclerosis (MS). In autopsy material from progressive MS patients, RGMa was found in active and chronic lesions, as well as in normal-appearing gray and white matter, and was expressed by cellular meningeal infiltrates. Levels of soluble RGMa in the cerebrospinal fluid were decreased in progressive MS patients successfully treated with intrathecal corticosteroid triamcinolone acetonide (TCA), showing functional improvements. In vitro, RGMa monoclonal antibodies (mAbs) reversed RGMa-mediated neurite outgrowth inhibition and chemorepulsion. In animal models of CNS damage and MS, RGMa antibody stimulated regeneration and remyelination of damaged nerve fibres, accelerated functional recovery, and protected the retinal nerve fibre layer as measured by clinically relevant optic coherence tomography. These data suggest that targeting RGMa is a promising strategy to improve functional recovery in MS patients.
Repulsive Guidance Molecules (RGMs) are members of a three gene family (in vertebrates) composed of RGMa, RGMb, and RGMc (also called hemojuvelin). RGMa has been implicated to play an important role in the developing brain and in the scar tissue that forms after a brain injury. For example, RGMa helps guide Retinal Ganglion Cell(RGC) axons to the midbrain. It has also been demonstrated that after induced spinal cord injury RGMa accumulates in the scar tissue around the lesion. Further research has shown that RGMa is an inhibitor of axonal outgrowth. Taken together, these findings highlight the importance of RGMa in axonal guidance and outgrowth. In this study they made a blocker of RGMa and this facilitated recovery and may have stimulated nerve outgrowth. It is open source so you can all read the paper.It will have the same problem as the anti-Lingo in that it has to get into the CNS (Biogen claim that it is the 0.1% that gets in that does the business.) However very encouraging