New Therapies for Neurological Ion Channel and Transporter Disorders
Treat-ION represents a network of clinicians and scientists across Germany to advance the knowledge about recognizing and treating rare neurological ion channel and transporter disorders. Those comprise a variety of neuropsychiatric diseases and symptoms including developmental delay, epilepsy, episodic and chronic ataxia, migraine and others, which often occur in combination or are caused by mutations in the same channels. Due to the common fundamental function of channels and transporters to regulate neuronal excitability and ionic homeostasis, pathophysiological and therapeutic principles are shared across diseases.
The main goal of the consortium is to translate findings from genetic and pathophysiological studies into rational, individualized therapies. Treat-ION will therefore focus on therapeutic studies in cellular, animal and human models, which will be complemented by in silico searches for new treatments, better predictions for the functional consequences of mutations for therapeutic purposes and cellular drug screens. The consortium will focus its efforts on approved and available ‘repurposed’ drugs. As a proof-of-principle, Treat-ION has successfully been performing n-of-1 trials and established three investigator-initiated trials in specific rare channel disorders with other funding, which will be of great value for the network.
The results of our research and the knowledge of experts will be systematically and directly delivered to patients through a structured molecular therapeutic board attached to the German academy of rare neurological diseases (DASNE).
- Coordination, Mol.-Therap. Board, and engaging with existing rare disease initiatives (Prof. Dr. Holger Lerche, Dr. Holm Graeßner, University of Tübingen
- Data integration and in silico precision medicine for neurological ion channel and transporter disorders (Prof. Dr. Yvonne Weber, RWTH Aachen)
- In silico characterization of disease-associated sites in ion channel and transporter proteins (Dennis Lal M.Sc., University of Cologne)
- Pathophysiology and new treatment options of CACNA1A disease variants in Drosophila melanogaster (Prof. Dr. Ludger Schöls, University of Tübingen)
- Novel therapies in KCNT1 channelopathies (PD Dr. Axel Neu, Dr. Dirk Isbrandt, University Hamburg-Eppendorf)
- Pathophysiology and new therapies for syndromes associated with glutamate transporter dysfunction (Prof. Dr. Christoph Fahlke, Forschungszentrum Jülich)
- Multimodal analysis of novel mouse models associated with glutamate transporter dysfunction Dr. Nikolaus Plesnila, Medical center of the University of Munich LMU)
- Pathophysiology and therapy in human neuronal models of KCNA2 channelopathies, Prof. Dr. Holger Lerche (University of Tübingen)
University of Tübingen
Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research
Tel.: +49 7071 29-80466
Fax +49 7071 29 4488.
Email: email@example.com Publications
1. December 2019 (Treat-ION)
SCN2A channelopathies: Mechanisms and models
Epilepsia. 2019 Dec;60 Suppl 3:S68-S76
Hedrich UBS, Lauxmann S, Lerche H.
8. November 2019 (Treat-ION)
Novel treatment approaches and pediatric research networks in status epilepticus
Epilepsy Behav. 2019 Dec;101(Pt B):106564. Epub 2019 Nov 8
Bialer M, Cross H, Hedrich UBS, Lagae L, Lerche H, Loddenkemper T.
1. October 2019 (Treat-ION)
Generation of an induced pluripotent stem cell (iPSC) line (HIHDNEi003-A) from a patient with developmental and epileptic encephalopathy carrying a KCNA2 (p.Thr374Ala) mutation
Stem Cell Res. 2019 Oct;40:101543.
Uysal B, Löffler H, Rosa F, Lerche H, Schwarz N
1. May 2019 (Treat-ION)
Establishment of a human induced pluripotent stem cell (iPSC) line (HIHDNEi002-A) from a patient with developmental and epileptic encephalopathy carrying a KCNA2 (p.Arg297Gln) mutation
Stem Cell Res. 2019 May;37:101445
Schwarz N, Uysal B, Rosa F, Löffler H, Mau-Holzmann UA, Liebau S, Lerche H.