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Sleep disorders as a warning signal: New findings on anti-IgLON5 disease
RUB Neurology reports on the anti-IgLON5 disease and a promising immunotherapy in JAMA Neurology.
Sleep disorders as a warning signal: New findings on anti-IgLON5 disease
Anti-IgLON5 disease, also known as anti-IgLON5 syndrome, is a rare neurological autoimmune disease characterized by the formation of antibodies against the IGLON5 protein. This disease manifests itself in a combination of sleep disorders, movement disorders and neurodegenerative symptoms. According to an international observational study that included 107 patients, research recommends using immunotherapy as early as possible to slow disease progression and improve the quality of life of those affected. The intravenous administration of immunoglobulins appears to be the most effective therapy, as scientists Prof. Dr. Ilya Ayzenberg and private lecturer Dr. Thomas Grüter from the neurology department at St. Josef Hospital, Clinic of the Ruhr University Bochum, presented in the renowned journal JAMA Neurology on August 4, 2025.
The symptoms of anti-IgLON5 disease are diverse and can cause significant disability if left untreated. Restlessness during sleep is often an early warning signal, followed by difficulty moving, swallowing and speaking. Diagnosing the disease is difficult because many of the symptoms can also occur in other diseases. This problem is further compounded by an unknown incidence, estimated at around 1 in 150,000.
Challenges in diagnosis
The diagnosis requires the detection of anti-IgLON5 antibodies in the serum and cerebrospinal fluid as well as specific examination methods, such as polysomnography to evaluate the sleep disorders and an MRI to rule out the diagnosis. The heterogeneity of symptoms makes recognizing the disease even more difficult. This complexity is compounded by the fact that less than 50% of patients respond to current immunotherapies, which to date also include corticosteroids, plasmapheresis, and rituximab.
The basic etiopathogenesis of anti-IgLON5 syndrome is incompletely understood. Nevertheless, the IGLON5 protein is suspected to play a central role in neuronal adhesion, neurogenesis and the maintenance of the blood-brain barrier. Misunderstandings regarding the mechanisms and involvement of the hyperphosphorylated tau protein raise additional questions that remain to be explored.
Research efforts and science news
The Charité – Universitätsmedizin Berlin is intensively dedicated to researching neurological autoimmune diseases. The clinical research group “BecauseY” investigates the development, diagnosis and treatment of neurological diseases influenced by antibodies. A comprehensive project will be implemented over four years with funding from the German Research Foundation (DFG) with almost 6.2 million euros. The main goal is to develop new diagnostic procedures and innovative therapies, while basic and clinical research are closely linked.
The research group plans to not only investigate the frequency and functions of autoantibodies in neurological diseases, but also to shed light on the influence of inflammatory processes on diseases such as dementia, epilepsy and autoimmune encephalitis. There is a great need for further studies on neurological and psychiatric symptoms associated with autoimmunity.