Smith C, Greenberg BM, Reynolds J, Mosavi-Hecht R, Semedo-Kuriki P, Benavides S, Zhang W, Wu Y, Adams G, Evers BM, Telesford KM, Yanev PG, Mettlen M, Stowe AM, Kerr D, Monson NL. A Patient-Derived Antibody Ameliorates Disease Severity in a Relapsing Remitting Murine Model of Multiple Sclerosis. Ann Neurol. 2026. doi: 10.1002/ana.78149.
Objective: Naturally occurring autoantibodies are commonly considered to be causative of autoimmune diseases or epiphenomena with no known biological impact. Although clinically beneficial autoantibodies have been described, there have been no naturally occurring anti-neuronal antibodies that have been found to be neuroprotective. Here, we identify a recombinant human antibody (TGM-010) derived from a patient with multiple sclerosis (MS) that binds human and mouse neurons, leading to beneficial effects.
Methods: TGM-010 was examined for its ability to be internalized by human and mouse neurons and protect neurons from death in vitro following a stress event. TGM-010 was also injected systemically into a relapsing-remitting model of experimental autoimmune encephalomyelitis (EAE) to examine its ability to impact disease score, extent of demyelination, and neuron frequency.
Results: TGM-010 demonstrates many novel characteristics including crossing the blood-brain barrier (BBB) and internalizing into neurons. TGM-010 also protects primary mouse neurons from death in vitro. In a mouse model of MS, TGM-010 ameliorates disease severity and is associated with improved neuronal survival.
Interpretation: This study identified a patient-derived neuron-binding autoantibody that crosses the BBB in mice and reduces neuron loss in a mouse model of MS. These data suggest that the human derived anti-neuronal antibody, TGM-010, may potentially be used to ameliorate neurodegeneration that underlies disability in neurodegenerative conditions.
Antibodies can be good or bad this antibody binds to nerves and was thought to have the potential to reduce nerve damage. The antibodies bind to the nucleus of nerves. They inject it into EAE mice the controls show subsequent worsening and those treated do not and them they do histology which being hard nosed tells us very little that makes sense because if the control has another disease episode it will lose nerves and as for demyelination you cant really tell there is any you need electronmicroscopy to show the nerves are alive. However interesting and it is not unknown that antibodies can have possitive impact, we showed this years ago.
Morris-Downes MM, Smith PA, Rundle JL, Piddlesden SJ, Baker D, Pham-Dinh D, Heijmans N, Amor S. Pathological and regulatory effects of anti-myelin antibodies in experimental allergic encephalomyelitis in mice. J Neuroimmunol. 2002; 125:114-24.
There was also an IgM antibody that was reported to promote myelin repair called rHIgM22. I hope that if the current antibody is developed it gets there quicker
Source: multiple-sclerosis-research.org