Jean-Philippe Loeffler. Inserm Research Director 
University of Strasbourg. Website
Faculty of Life Sciences/INSERM. Faculté de Médecine, Bâtiment 3, Etage 8, 11 rue Humann, 67085 Strasbourg, France.
Reseach subject
We aim at deciphering the pathological mechanisms that trigger amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We study the reciprocal relationships occurring between the central nervous system and the peripheral organs, with an emphasis on metabolic interactions.
Summary
ALS is the most frequent motor neuron disease, with 15,000 new patients each year in Europe and 140,000 worldwide. ALS develops as a progressive paralysis leading to death within 2-5 years of diagnosis. FTD is the second most frequent form of dementia, and progresses to death within a few years following diagnosis. In spite of some 20 years of preclinical research, ALS and FTD remain incurable. While the two diseases present with very different clinical signs, they may result from mutations affecting same genes.
Our lab aims at developing new therapeutic strategies and identifying both diagnostic and prognostic biomarkers that may further help assessing the benefits of clinical trials conducted on ALS and FTD patients. Our work thus intersects the disciplines of fundamental research and translational research.
We develop 5 complementary research axes:
1. Characterization of the neural pathways involved in energy metabolism defects in ALS.
2. Identification of biomarkers for ALS and FTD via high-throughput screening.
3. Cerebral cortex and corticospinal motor neurons in ALS.
4. Characterization of the peripheral alterations in ALS and FTD, with a focus on the neuromuscular junctions.
5. Development and characterization of new ALS and FTD animal models.
Publications
- Scekic-Zahirovic J, Oussini HE, Mersmann S, Drenner K, Wagner M, Sun Y, Allmeroth K, Dieterlé S, Sinniger J, Dirrig-Grosch S, René F, Dormann D, Haass C, Ludolph AC, Lagier-Tourenne C, Storkebaum E, Dupuis L. Motor neuron extrinsic mechanisms contribute to the pathogenesis of FUS-associated amyotrophic intrinsic and lateral sclerosis. Acta Neuropathol. 2017 Feb 28. doi: 10.1007/s00401-017-1687-9.
- Vernay A, Therreau L, Blot B, Risson V, Dirrig-Grosch S, Waegaert R, Lequeu T, Sellal F, Schaeffer L, Sadoul R, Loeffler JP, René F. A transgenic mouse expressing CHMP2Bintron5 mutant in neurons develops histological and behavioural features of amyotrophic lateral sclerosis and frontotemporal dementia. Hum Mol Genet. 2016 Aug 1;25(15):3341-3360.
- Vercruysse P, Sinniger J, El Oussini H, Scekic-Zahirovic J, Dieterlé S, Dengler R, Meyer T, Zierz S, Kassubek J, Fischer W, Dreyhaupt J, Grehl T, Hermann A, Grosskreutz J, Witting A, Van Den Bosch L, Spreux-Varoquaux O; GERP ALS Study Group., Ludolph AC, Dupuis L. Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis. Brain. 2016 Apr;139(Pt 4):1106-22.
- Palamiuc L, Schlagowski A, Ngo ST, Vernay A, Dirrig-Grosch S, Henriques A, Boutillier AL, Zoll J, Echaniz-Laguna A, Loeffler JP, René F. A metabolic switch toward lipid use in glycolytic muscle is an early pathologic event in a mouse model of amyotrophic lateral sclerosis. EMBO Mol Med. 2015 Mar 27;7(5):526-46.
- Henriques A, Croixmarie V, Priestman DA, Rosenbohm A, Dirrig-Grosch S, D’Ambra E, Huebecker M, Hussain G, Boursier-Neyret C, Echaniz-Laguna A, Ludolph AC, Platt FM, Walther B, Spedding M, Loeffler JP, Gonzalez De Aguilar JL. Amyotrophic lateral sclerosis and denervation alter sphingolipids and up-regulate glucosylceramide synthase. Hum Mol Genet. 2015 Dec 20;24(25):7390-405.
