DZNE Foundation honors two young researchers with Best Paper Award 2024

500 euros each for outstanding research at the DZNE site in Munich on harmful immune cells and a therapeutic approach against protein deficiency in FTD.

Last year, the DZNE Foundation announced a prize for the best scientific publication for the third time. For this “Best Paper Award 2024”, publications by first authors from our Munich site could be submitted. The papers should have been published in renowned international journals within the last twelve months prior to the call for submissions and should have made a significant contribution to research into the development, diagnosis and treatment of neurodegenerative diseases or the care of people affected.

Research is almost always a team effort, which is why scientific publications generally have several authors. However, the so-called first authors, to whom the “Best Paper Award” is dedicated, have a prominent position: they have shouldered most of the work.

The award ceremony recently took place at the DZNE Munich: Shreeya Kedia (RG Prof. Mikael Simons) was honored for the article “T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis” published in the journal “Nature Neuroscience”. And Marvin Reich, Ph.D. (Stanford University, Wyss-Coray Lab, previously RG Prof. Christian Haass) received the award for his paper “Peripheral expression of brain-penetrant progranulin rescues pathologies in mouse models of frontotemporal lobar degeneration“, which was published in “Science Translational Medicine”.

Basis for novel therapies in Alzheimer’s: preserving the protective sheath of nerve fibers

As the brain ages, the oligodendrocytes – cells that form a protective sheath around nerve fibers called the “myelin sheath” and enable rapid signal transmission in the brain – become damaged and inflamed. It is not yet fully understood how this damage contributes to the development of neurodegenerative diseases like Alzheimer's. To address this question, cell biologist Shreeya Kedia used mouse models to study mechanisms of Alzheimer's disease: She found that damage to the protective layer of nerve fibers is triggered by amyloid protein deposits – a characteristic feature of Alzheimer's.

Kedia also discovered an increase in certain immune cells, so-called cytotoxic T cells (CD8+ T cells), which trigger inflammatory processes (neuroinflammation). She used antibodies to remove these immune cells in order to gain a better understanding of their effect: this reduced the neuroinflammation and improved learning and memory performance as well as the condition of the myelin sheath.

Conclusion: Shreeya Kedias' research provides insights into how these immune cells contribute to neuroinflammation. If these findings are confirmed in further studies in humans, they could form the basis for novel therapies to delay the progression of Alzheimer's disease: treatments that aim to preserve the myelin sheath by reducing inflammation. In the future, Kedia wants to investigate the role of cytotoxic T cells in other neurodegenerative diseases.

New option against frontotemporal dementia: innovative treatment approach

Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by loss of memory, speech disorders and changes in behavior and personality. There is currently no cure for FTD. It is one of the most common forms of early-onset dementia, often occurring before the age of 65. The disease is often triggered by a shortage of a certain protein called progranulin, which is produced in insufficient amounts in many affected individuals for genetic reasons. A lack of progranulin increases the risk of developing FTD (especially the subtype FTLD-GRN).

A major challenge with previous therapeutic approaches is that progranulin is difficult to replace in sufficient amounts in the brain, as this requires regular injections into the bloodstream or direct brain injections. The aim of biochemist Marvin Reich was to find a way to deliver this protein to the brain more effectively to compensate for its deficiency.

In his study, Marvin Reich, in collaboration with the biotech company Denali Therapeutics, developed a new treatment approach for FTD: This gene therapy enables the body to produce modified progranulin itself, which is more easily transported to the brain, avoiding inflammation or difficulties in distributing the protein in the brain. Reich's method ensures that the protein is produced permanently by the body itself and reaches the brain without the need for periodic or direct injections.

In so-called mouse models of FTLD-GRN, this treatment proved successful and a single injection was sufficient to increase the amount of progranulin in the brain stably and evenly over a long period of time. In addition, Reich found that several disease symptoms improved, such as movement disorders, problems with fat metabolism, difficulties in removing harmful proteins in cells, and nerve cell damage.

Conclusion: The results show that this therapeutic approach can have long-lasting and promising effects on the brain without the need for repeated or direct injections of progranulin. Reich's research thus provides the basis for clinical trials to test the therapy in humans and to examine its long-term safety and efficacy.

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