- Source: Matthis Synofzik
Matthis Synofzik is a German translational neurologist and research neuroscientist. He is Professor (apl. Prof.) for Translational Genomics of Neurodegenerative Disease and leads the research division of Translational Genomics of Neurodegenerative Diseases at the Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Germany.
Education
Synofzik studied Philosophy at the Munich School of Philosophy and at the University of Tübingen. Concurrently, he studied Medicine. He earned his clinical medical qualification (2006), as well as was awarded his Philosophy degree (Magister artium) from the University of Tübingen. In 2008, he submitted his thesis in the field of cognitive neuroscience and was awarded his doctorate (Dr. med.) at the University of Tübingen. In 2013, he completed his board certification in clinical neurology at the University of Tübingen. In 2014, he was appointed as a consultant neurologist with a main focus on neurodegenerative diseases, and established his research laboratory, focusing on genetic, molecular and cognitive neuroscience levels of systems neurodegeneration. In 2015, he completed his (Habilitation) (Qualification for full professorship) in Neurology at the University of Tübingen titled Clinics and Genetics of autosomal-recessive ataxias (Klinik und Genetik autosomal-rezessiver Ataxien) under the guidance of Ludger Schöls and Thomas Gasser.
Research interests
His work, which has been widely published and cited, focuses on understanding the mechanisms of neurodegenerative diseases, particularly in the areas of hereditary ataxias, motor neuron diseases (ALS; hereditary spastic paraplegias), frontotemporal dementia and Alzheimer’s Disease. In his next-generation precision medicine and translational neuroscience approach, he combines next-generation genomics, biomarker development of ultra-sensitive fluid protein biomarkers, digital-motor biomarkers, and disease progression modeling to develop and investigate individualized molecular precision therapies. In his clinical practice, he specializes in diagnosing and treating patients with hereditary neurodegenerative disorders like hereditary ataxias, motor neuron diseases, frontotemporal dementia and Alzheimer’s Disease. He focuses on developing and applying advanced therapies, including RNA therapies and personalized medicine approaches. His clinical interests also extend to other rare and complex neurological disorders, where he combines diagnostic precision with cutting-edge research to develop individualized treatment plans for his patients.
Synofzik is known for his contributions to genetic research on ataxias and spastic paraplegias. He leads large-scale genomic initiatives like the PREPARE GENESIS database, which holds over 3,000 next-gen sequencing datasets for ataxia. This work has resulted in the discovery of over 20 novel genes related to ataxia and spasticity (e.g., DNAJC3, KCNA2, and PRDX3.)
For example, in a recent publication, Synofzik helped to identify a novel genetic cause of late-onset cerebellar ataxia—GAA repeat expansions in the FGF14 gene - a previously unexplored cause of disease; and then set forth to demonstrate that this novel disease might be treatable by an already marketed drug (4-Aminopyridine). It highlights the importance of examining deep intronic regions in genetic diagnostics, expanding the scope of mutation types considered in late-onset ataxia cases. The discovery of this repeat expansion underlying a treatable disease (as shown by Synofzik) may improve genetic screening and diagnosis for patients with unexplained ataxia, potentially leading to more targeted therapies. Similarly, in the field of frontotemporal dementia, Synofzik and colleagues demonstrated the genetic underpinnings of frontotemporal dementia in a 2018 paper.
His group has also pioneered the use of neurofilament light chain and other protein biomarkers to track disease progression in neurodegenerative conditions, particularly in frontotemporal dementia and ataxias. These biomarkers are vital for understanding disease stages and measuring treatment effects. As part of a larger body of work on these biomarker, a large longitudinal study demonstrated that serum neurofilament light and phosphorylated neurofilament heavy can stratify the presymptomatic phase of genetic frontotemporal dementia. These biomarkers track disease progression well before clinical symptoms appear. The findings provide crucial tools for early detection and for designing preventive or early-stage clinical trials for frontotemporal dementia, which is essential for slowing or halting disease progression before significant neurological damage occurs. Synofzik has shown similar metrics of these biomarkers in ataxias and motor neuron diseases.
He also specializes in digital-motor biomarker development, creating techniques to capture movement data using body-worn sensors and smartphones to monitor neurodegenerative conditions also remotely in patients’ real life. He is a leader in developing individualized antisense oligonucleotides (ASOs), as part of a specific innovative personalized RNA therapy platfom approach for ultra-rare neurological diseases. This 1Mutation 1 Medicine (1M1M) initiative, co-chaired by Synofzik, focuses on creating tailored therapies for patients with specific genetic mutations, representing a novel approach to precision medicine in neurology. In a 2022 paper, Synofzik and colleagues set the stage for a genetic, regulatory, and ethical path for individualized ASO therapies in Europe.
Synofzik has contributed to the creation of multimodal progression models for diseases like frontotemporal dementia and ataxias, incorporating data from fluid biomarkers, clinical outcomes, and neuroimaging. These models are essential for understanding disease dynamics and preparing for clinical trials.
Synofzik’s work thus bridges basic neuroscience, clinical research, and translational applications, advancing the diagnosis and treatment of complex neurodegenerative diseases. His contributions significantly enhance the understanding of the genetic underpinnings and biomarker-based stratification in neurodegenerative diseases, advancing precision medicine and early intervention strategies.
Career
Following the completion of his Habilitation, Synofzik added clinical subspecialization in Geriatrics (2016) and Palliative Medicine (2018). In 2018, he was appointed professor (apl. Prof.) at the University of Tuebingen. In 2020, he assumed leadership of the research division of Translational Genomics of Neurodegenerative Diseases at the Hertie Institute for Clinical Brain Research.
Prof. Synofzik is actively engaged in the clinical, research and ethics community on a local, national and international level:
Chair - Ataxia Global Initiative (AGI)
Coordinator - European PROSPAX consortium: an integrated multimodal progression chart in spastic ataxias
Coordinator - European EVIDENCE-RND consortium: Creating robust evidence for longitudinal progression changes and treatment effects in ultra-rare neurological diseases
Task leader and Work package co-leader of the European ERDERA consortium: European Rare Disease Research Alliance
Steering Committee - 1Mutation 1 Medicine (1M1M)
Steering Committee - N-of-1 collaborative (N1C)
Co-Director - Gene and RNA Therapy Center (GRTC) - University of Tübingen
Member of the Medical Advisory Board - German Society for Friedreich Ataxia
Member - German Academy for Ethics in Medicine (AEM)
Awards
Synofzik has received several awards and honors throughout his career, including:
FARA - Bronya J. Keats International Research Collaboration Award on Friedreich Ataxia - 2017
Else-Kröner Fresenius Stiftung - Clinical Scientist Scholarship - 2016-2018
German Hereditary Ataxia Society (DHAG) - Heredo-Ataxia Prize - 2012
University of Tübingen - Attempto-Award for the Neurosciences - 2009
External links
https://www.medizin.uni-tuebingen.de/de/das-klinikum/mitarbeiter/profil/1527
https://www.hih-tuebingen.de/en/research/independent-research-groups/translational-genomics/
https://www.semanticscholar.org/author/M.-Synofzik/143813340
https://www.researchgate.net/profile/Matthis-Synofzik
https://orcid.org/0000-0002-2280-7273
https://scholar.google.com/citations?hl=en&user=sI0F658AAAAJ
https://www.adscientificindex.com/scientist/matthis-synofzik/1787576
