Novel Mechanisms Causing Lafora Disease – Rare Diseases 2010


Für den Inhalt der Angaben zeichnet die Projektleitung verantwortlich.


This project is one of the five winners of the call 2010 «Rare Diseases - New Approaches».

Project partners: ETH Zürich; University of Kentucky, Lexington, USA


Projekt-Nr.: GRS-049/10
Förderbeitrag: CHF 250'000
davon Löhne: CHF 200'000
Bewilligung: 27.10.2010
Dauer: 04.2011 - 04.2015
Handlungsfeld: Rare Diseases, seit 2009

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Projekt nummerGRS-058/14 BudgetCHF 400'000 VerantwortlichChristoph Hess Laufzeit04.2015 - 03.2018

Towards Small Molecule Intervention in Cockayne Syndrome – Rare Diseases 2014
Projekt nummerGRS-057/14 BudgetCHF 480'000 VerantwortlichNicolas Thomä Laufzeit07.2015 - 06.2018

Schweizer Register für Seltene Krankheiten
Projekt nummerGRS-030/14 BudgetCHF 50'000 VerantwortlichMatthias Baumgartner Laufzeit11.2014 - 03.2017

Nrf2 and Netherton Syndrome – Rare Diseases 2013
Projekt nummerGRS-052/13 BudgetCHF 380'000 VerantwortlichMatthias Schäfer Laufzeit06.2014 - 05.2018

New Drug Targets to Treat Polycystic Kidney Disease (ADPKD) – Rare Diseases 2013
Projekt nummerGRS-051/13 BudgetCHF 480'000 VerantwortlichDaniel Constam Laufzeit03.2014 - 07.2017

Treatment for Cutaneous Lupus Erythematosus – Rare Diseases 2013
Projekt nummerGRS-050/13 BudgetCHF 450'000 VerantwortlichJean Pieters Laufzeit01.2014 - 11.2017

Neurodegeneration in Rasmussen Encephalitis – Rare Diseases 2013
Projekt nummerGRS-049/13 BudgetCHF 490'000 VerantwortlichDoron Merkler Laufzeit04.2014 - 09.2017

Treating Dominant Optic Athrophy – Rare Diseases 2013
Projekt nummerGRS-048/13 BudgetCHF 300'000 VerantwortlichAlbert Neutzner Laufzeit07.2014 - 11.2017

Optogenic Vision Restoration – Rare Diseases 2012
Projekt nummerGRS-039/12 BudgetCHF 500'000 VerantwortlichBotond Roska Laufzeit12.2012 - 08.2016

Uromodulin-Associated Kidney Diseases – Rare Diseases 2012
Projekt nummerGRS-038/12 BudgetCHF 490'000 VerantwortlichOlivier Devuyst Laufzeit03.2013 - 08.2016

Inducing Immunological Tolerance to Galsulfase – Rare Diseases 2012
Projekt nummerGRS-037/12 BudgetCHF 300'000 VerantwortlichJeffrey A. Hubbell Laufzeit04.2013 - 05.2016

Diseases of Imprinting – Rare Diseases 2012
Projekt nummerGRS-036/12 BudgetCHF 400'000 VerantwortlichDidier Trono Laufzeit01.2013 - 06.2016

Molecular Basis of Pseudomonas aeruginosa Persistence during Chronic Infections of Cystic Fibrosis Airways – Rare Diseases 2012
Projekt nummerGRS-035/12 BudgetCHF 370'000 VerantwortlichUrs Jenal Laufzeit02.2013 - 12.2016

Role of snoRNAs in the Development of Prader Willi Syndrome – Rare Diseases 2011
Projekt nummerGRS-046/11 BudgetCHF 110'000 VerantwortlichShivendra Kishore Laufzeit02.2012 - 01.2013

Lymphedema-Distichiasis – Rare Diseases 2011
Projekt nummerGRS-045/11 BudgetCHF 500'000 VerantwortlichTatiana Petrova Laufzeit03.2012 - 09.2015

Chronic Mucocutaneous Candidiasis - Rare Diseases 2011
Projekt nummerGRS-044/11 BudgetCHF 500'000 VerantwortlichSalomé Leibundgut-Landmann Laufzeit07.2012 - 05.2017

Vaccination for the Prevention and Cure of Inflammatory Bowel Disease – Rare Diseases 2011
Projekt nummerGRS-043/11 BudgetCHF 190'000 VerantwortlichAnne Müller Laufzeit02.2012 - 11.2015

Therapies for Dysferlinopathies - Rare Diseases 2011
Projekt nummerGRS-042/11 BudgetCHF 480'000 VerantwortlichMichael Sinnreich Laufzeit04.2012 - 03.2015

Prodrug Platform for Rare Colonic Diseases - Rare Diseases 2011
Projekt nummerGRS-041/11 BudgetCHF 300'000 VerantwortlichJean-Christophe Leroux Laufzeit05.2012 - 07.2015

Novel Mechanisms Causing Lafora Disease – Rare Diseases 2010
Projekt nummerGRS-049/10 BudgetCHF 250'000 VerantwortlichOliver Kötting Laufzeit04.2011 - 04.2015

Rescue of Dysfunctional RNA Processing in Spinal Muscular Atrophy – Rare Diseases 2010
Projekt nummerGRS-048/10 BudgetCHF 400'000 VerantwortlichChristoph Handschin Laufzeit07.2011 - 11.2014

Identification of the Genomic Cause of Rare Autosomal Recessive Disorders Using Consanguinity – Rare Diseases 2010
Projekt nummerGRS-047/10 BudgetCHF 500'000 VerantwortlichStylianos Antonarakis Laufzeit01.2011 - 02.2015

Role of Macroautophagy in CGD and Correction of the Defect – Rare Diseases 2010
Projekt nummerGRS-046/10 BudgetCHF 390'000 VerantwortlichJanine Reichenbach Laufzeit07.2011 - 04.2015

Towards a better mechanistic understandig of Friedreich’s Ataxia – Rare Diseases 2010
Projekt nummerGRS-045/10 BudgetCHF 498'000 VerantwortlichMarc Bühler Laufzeit02.2011 - 05.2014

Identification of new factors implicated in genetic gonadal disorders – Rare Diseases 2009
Projekt nummerGRS-048/09 BudgetCHF 450'000 VerantwortlichSerge Nef Laufzeit04.2010 - 12.2013

Seltene Nervenkrankheit – Rare Diseases 2009
Projekt nummerGRS-047/09 BudgetCHF 340'000 VerantwortlichThorsten Hornemann Laufzeit03.2010 - 09.2013

Gene hunting for recessive hereditary peripheral neuropathies by recent and highly-parallel technologies – Rare Diseases 2009
Projekt nummerGRS-046/09 BudgetCHF 440'000 VerantwortlichCarlo Rivolta Laufzeit07.2010 - 03.2014

Genetic screening for disease-causing mutations in familial polycythemia using next generation DNA sequencing – Rare Diseases 2009
Projekt nummerGRS-045/09 BudgetCHF 300'000 VerantwortlichRadek Skoda Laufzeit04.2010 - 12.2012

Towards preventing nodule formation in Hyaline Fibromatosis patients – Rare Diseases 2009
Projekt nummerGRS-044/09 BudgetCHF 450'000 VerantwortlichGisou van der Goot Laufzeit04.2010 - 09.2013

Kommunikation Programm «Rare Diseases»
Projekt nummerGRS-063/08 BudgetCHF 85'000 VerantwortlichThomas Pfluger Laufzeit01.2009 - 12.2009


Dr. Oliver Kötting, Oberassistent, ETH Zurich, Institute of Plant, Animal and Agroecosystem Sciences, Universitätsstrasse 2, LFW E 51, 8092 Zürich (Schweiz), koetting@ethz.notexisting@nodomain.comch


Lafora disease (LD) is an inherited autosomal recessive progressive myoclonus epilepsy. It typically presents as a single seizure in the second decade of the patient’s life and is followed by progressive neurological deterioration and usually death within ten years of the onset. LD cannot be managed by medication and there is no known cure. Approximately 88% of the LD cases are caused by mutations in either of the two genes encoding for the proteins laforin and malin. The mutations that cause LD in the remaining 12% of the cases are not known. A characteristic of LD is the accumulation of insoluble deposits that contain an aberrant form of glycogen (the major human energy reserve) within muscle and nerve cells. It is hypothesized that these so-called Lafora bodies (LBs) trigger the development of the LD symptoms. Little is known about the mechanisms that lead to LB formation, though. Two different mechanisms have been proposed. Either excessive glycogen phosphorylation or an imbalance between glycogen synthesizing enzymes could result in the accumulation of insoluble LBs. However, up to know the mechanism responsible for glycogen phosphorylation is unknown and the LB structure is only insufficiently characterized.

Was ist das Besondere an diesem Projekt?

Gebert Rüf Stiftung was supporting this project because of its innovative strategy for the identification of novel factors involved in Lafora disease formation. The complementary approach applied state-of-the-art analytical techniques and led to a better molecular and biochemical understanding of the disease. It thus paved the way to potentially develop new forms of Lafora disease treatment.


In order to identify novel protein factors involved in LB formation and/or glycogen phosphorylation, we took a proteomics approach. We isolated native LBs from various tissues of a LD mouse model (mice that are deficient in laforin) and identified bound proteins by mass spectrometry. We found a number of proteins known to be involved in glycogen metabolism indicating the feasibility of our approach. Interestingly, we also identified proteins, which were not directly assigned to glycogen metabolism before. These are likely new proteins involved in glycogen phosphorylation, LB formation and/or LD establishment, thus representing new potential targets for LD diagnostics and/or therapy. Our future research will hopefully unravel the in vivo role of these proteins with particular emphasis on their function in Lafora disease.


In preparation


Not yet


Oliver Kötting’s website, ETH Zürich:
Plant Biochemistry group, ETH Zürich:
Matthew Gentry’s website, University of Kentucky:
The Lafora Gene Mutation Database:
Lafora Children Research Fund:

Am Projekt beteiligte Personen

Dr. Oliver Kötting, ETH Zürich, project leader
Dr. Elham Schokraie, ETH Zürich, postdoc
Prof. Dr. Matthew Gentry, University of Kentucky
Prof. Dr. Samuel C. Zeeman, ETH Zürich

Letzte Aktualisierung dieser Projektdarstellung