New glimmer of hope: immune activation detected in spastic paraplegia!

New glimmer of hope: immune activation detected in spastic paraplegia!

The latest developments in the research of spastic paraplegia type 15 are the focus of an interdisciplinary project led by Prof. Dr. Elvira Mass from the LIMES Institute at the University of Bonn and Dr. Marc Beyer from the German Center for Neurodegenerative Diseases (DZNE). This disease affects neurons in the brain that are responsible for controlling movement and causes uncontrolled twitching and paralysis that usually begins in late childhood. The exact trigger for the brain cell death is currently unknown, but a defect in the SPG15 gene, which is responsible for an important protein, appears to play a key role. According to the researchers, massive inflammation occurs before the first neuronal damage occurs, which indicates an early progression of the disease.

The study focuses in particular on the role of the immune system, with researchers examining the behavior of microglia - the immune cells in the brain - and immune cells from the bone marrow. Microglia migrate to the brain during embryonic development, while other immune cells can reach there via the bloodstream. A notable part of the research involves labeling bone marrow cells with a fluorescent dye to distinguish them from microglia. The microglia change early in the development of the disease and transform into so-called “disease-associated microglia”, which release messenger substances and promote the activation of cytotoxic T cells. This interaction increases the inflammatory process, suggesting that early immune activation characterizes the first phases of the disease and not the loss of motor neurons.

Neurological autoimmune diseases in focus

In addition, research at the Charité – Universitätsmedizin Berlin sheds light on the development, diagnosis and treatment of neurological diseases that are influenced by autoantibodies. The clinical research group “BecauseY” is funded by the German Research Foundation (DFG) with 6.2 million euros over four years. This group aims to investigate the frequency, targets and functions of neuron-affected autoantibodies, which can potentially trigger diseases such as dementia, epilepsy, psychoses and autoimmune encephalitis. Prof. Dr. Matthias Endres points out that the need for research into autoimmunity in neurology and psychiatry is still great.

As part of the research, a center will be set up that combines basic and clinical research. Patient samples will be collected here in order to develop new diagnostic tests and innovative therapeutic methods. Researchers led by Prof. Dr. Harald Prüß, plan to recreate autoantibodies and understand how they work. The possibilities with which autoantibodies can be treated in the future could also provide insights into other diseases such as stroke and neurodegenerative dementia.

Potential therapeutic approaches

The results of this research are promising and highlight the importance of interdisciplinary collaboration. The findings from the study on spastic paraplegia type 15 and neurological autoimmune diseases could lead to new therapeutic perspectives. These include, among other things, drugs to suppress the immune system, which can be important not only in spastic paraplegia, but also in other neurodegenerative diseases such as Alzheimer's.

Current developments show that medicine is on a comprehensive path to better understanding the causes and mechanisms of neurological diseases. The combination of basic research, clinical application and interdisciplinary collaboration is crucial to developing new therapies and sustainably improving the quality of life of those affected.

For more information about the current study and its results, visit University of Bonn, the National Institutes of Health as well as the Charité – University Medicine Berlin.