Tracing a New MS-like Disease

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Research over the past several years has shown that the condition long referred to as multiple sclerosis (MS) is likely to encompass a whole spectrum of different inflammatory autoimmune diseases of the central nervous system (CNS) – the brain and spinal cord. In these conditions, the immune system attacks different molecular targets, known as antigens.

A team of researchers at LMU University Hospital, working with national and international collaborators and co-led by Prof. Edgar Meinl and Prof. Simone Mader (now based at Friedrich-Alexander-Universität Erlangen-Nürnberg and University Hospital Erlangen, and a BMC alumna), has now identified one such antigen. “These findings expand our understanding of autoimmune reactions against the brain itself, with potential implications for diagnosis and treatment,” says Edgar Meinl. The study is published in the journal Science Translational Medicine.

When recurrent or persistent inflammation occurs in the central nervous system and certain other criteria are met, most patients are diagnosed with multiple sclerosis. However, research in recent years has shown that some patients have diseases that resemble classical MS but differ from it and constitute distinct diagnoses. These include MOGAD (MOG antibody-associated disease) and NMOSD (neuromyelitis optica spectrum disorder). Distinguishing these conditions from MS has been made possible by detecting specific autoantibodies directed against antigens in the CNS. For the vast majority of patients diagnosed with MS or an MS-like disease, however, the precise targets of the autoimmune response remain unknown.

The Munich researchers and their collaborators have now identified an antigen in the brain that is targeted by the misdirected immune response in some patients with MS or MS-like diseases. The study was prompted by a patient seen at the neuroimmunology outpatient clinic at the Institute of Clinical Neuroimmunology, headed by Prof. Tania Kümpfel. The patient had inflammation of the spinal cord, suggesting an antibody-mediated disease. However, none of the known autoantibodies could be detected. The research team found antibodies in the patient’s blood that bound to brain tissue – specifically to astrocytes, support cells that surround blood vessels in the CNS.

Identifying the target structure

Using advanced methods, the researchers were able to identify the target structure precisely. It is a protein called MLC1, which is found on the surface of astrocytes. Using a newly developed test, the researchers detected antibodies against MLC1 in the blood of four out of around 300 patients diagnosed with MS or an MS-like disease. In a range of laboratory experiments, the team also demonstrated that antibodies against MLC1 can destroy astrocytes and increase inflammation in the spinal cord.

The new findings illustrate, says Tania Kümpfel, “that the spectrum of diseases that present similarly to multiple sclerosis is continuing to expand. This is also reflected in updated diagnostic criteria. This is an important foundation for treating these diseases with increasing precision and effectiveness.” This development is already happening. According to Kümpfel, four medicines are now approved for NMOSD in Germany, and they are highly effective. A recent clinical trial has shown that one of these drugs is also effective in MOGAD. Detecting autoantibodies can therefore help to enable more targeted treatment.

The co-leads of the study

• Prof. Simone Mader, Head of the Translational Immunology Division, University Hospital Erlangen
• Prof. Monika Bradl, Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna
• PD Dr Naoto Kawakami, Institute of Clinical Neuroimmunology, LMU University Hospital
• Clinical team of the neuroimmunology outpatient clinic, headed by Prof. Tania Kümpfel, Institute of Clinical Neuroimmunology, LMU University Hospital

Publication: Hoi Kiu Wong et al.: Antibodies against MLC1 found in patients with NMOSD-like disease mediate astrocytopathy in rodent models. Science Translational Medicine, 2026

Source: LMU University Hospital