Bispecific antibodies show effectiveness in treating autoimmune neuropathy in two patients

Clinical Cases of Treatment

Christian Geiss and his team from Friedrich Schiller University Jena detailed two cases of Teclumab application for the treatment of chronic autoimmune neuropathy. The first patient, a 65-year-old woman, had suffered from chronic peripheral myelopathy related to kappa-immunoglobulin M (IgM-kappa) for over five years. Her symptoms included loss of sensation in the extremities, leg and back pain, and balance problems. She could walk no more than 300 meters with support, had difficulty climbing stairs, and could not stand for long periods. Examinations revealed peripheral nerve edema and clear signs of demyelination. Despite treatment with high doses of glucocorticoids, immunoglobulins, and plasmapheresis, the disease continued to progress.

After four injections of Teclumab, this woman's condition significantly improved: her walking distance increased, grip strength rose, and neuropathy symptoms decreased according to clinical scales. Subjective indicators, including quality of life, pain, and fatigue, also improved. Nerve conduction parameters, distal latency, and muscle action potential improved, and nerve edema resolved. These positive changes were maintained during nine months of observation. A decrease in the serum level of neurofilament light chains (a marker of neuronal damage) was noted, the disappearance of paraprotein and its absence for nine months, as well as the disappearance of free light kappa-chains of immunoglobulins, although they later began to be detected again. Immediately after therapy, there was a depletion of B-lymphocytes, followed by their repopulation, mainly through naive cells. Side effects were moderate and controlled.

The second patient, aged 73, had chronic peripheral myelopathy associated with anti-myelin-associated glycoprotein (MAG) antibodies, lasting 13 years. Her condition was characterized by sensorimotor ataxia and distal sensorimotor problems. Initially, high doses of glucocorticoids helped reduce sensory deficits; however, the disease subsequently worsened despite receiving steroids, immunoglobulins, plasmapheresis, and rituximab, leading to ataxia, leg paresis, and frequent falls with fractures. Instrumental examinations showed an absence of motor and sensory responses in the leg nerves, marked slowing of conduction in arm nerves, and multifocal nerve edema.

Following a course of four Teclumab injections, her walking distance increased more than sixfold by the sixth month, symptoms decreased on clinical scales, nerve conduction improved, and nerve edema significantly reduced. Pain and other neuropathic manifestations decreased, improving quality of life. Similar to the first patient, paraprotein disappeared and was not detected for six months of observation, and the neurofilament light chain level decreased, while anti-MAG antibodies were not found. Following B-lymphocyte depletion, their population recovered. Side effects were also moderate and controlled, and clinical and instrumental improvements remained stable without signs of relapse for six months.

Study Conclusions

The results of this pilot experiment indicate the significant therapeutic potential of T-cell recruitment-based therapy for chronic autoimmune neuropathy, and potentially for other neuroimmunological disorders, which requires further study. It should be noted that previously another German research group achieved success in treating two patients with severe autoimmune polyneuropathy using T-lymphocytes with chimeric antigen receptors (CAR-T cells), allowing some patients to begin walking.