Speaker
Ludo Van Den Bosch
All Events
Therapeutic effects of HDAC6 inhibition in peripheral neuropathies and amyotrophic lateral sclerosis (ALS)
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Teams
Description
Abstract Ludo research focuses on the cause, mechanism and treatment options for neurodegenerative diseases. In particular, he studies amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) and its relation to frontotemporal dementia, as well as Charcot-Marie-Tooth disease (an axonal peripheral neuropathy). To this end, he performs genetic studies, study in vitro models and fruit fly, fish, mouse and rat models, and has an intensive clinical research program. He aims to translate results from genetic and animal studies to biomarker aspects and treatment strategies. His group has contributed significantly to the development of in vitro motor neuron models (including iPSC-derived motor neurons). The fish model for ALS that he developed, has found its way to many other groups, and allowed genetic screens for the identification of modifiers. These research activities have resulted in many papers in top journals.
HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease. Nature Medicine, 17 (8), 968-974. van Outryve d’Ydewalle, C., Krishnan, J., Chiheb, D., Van Damme, P., Irobi, J., Kozikowski, A.P., Vanden Berghe, P., Timmerman, V., Robberecht, W., Van Den Bosch, L. (2011).
HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients. Nature Communications. Guo, W., Naujock, M., Fumagalli, L., Vandoorne, T., Baatsen, P., Boon, R., Ordovás, L., PATEL, S., Welters, M., Vanwelden, T., Geens, N., Tricot, T., Benoy, V., Steyaert, J., Lefebvre-Omar, C., Boesmans, W., Jarpe, M., Sterneckert, J., Wegner, F., Petri, S., Bohl, D., Vanden Berghe, P., Robberecht, W., Van Damme, P., Verfaillie, C., Van Den Bosch, L. (2017).
HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients. Nature Communications, 8 (1), Art.No. ARTN 861. Guo, W., Naujock, M., Fumagalli, L., Vandoorne, T., Baatsen, P., Boon, R., Ordovás, L., PATEL, S., Welters, M., Vanwelden, T., Geens, N., Tricot, T., Benoy, V., Steyaert, J., Lefebvre-Omar, C., Boesmans, W., Jarpe, M., Sterneckert, J., Wegner, F., Petri, S., Bohl, D., Vanden Berghe, P., Robberecht, W., Van Damme, P., Verfaillie, C., Van Den Bosch, L. (2017).
HDAC6 is a therapeutic target in mutant GARS-induced Charcot-Marie-Tooth disease. Brain, 141 (3), 673-687 Benoy, V., Van Helleputte, L., Prior, R.C., d’Ydewalle, C., Haeck, W., Geens, N., Scheveneels, W., Schevenels, B., Vanden Berghe, P., Van Damme, P., Robberecht, W., Van Den Bosch, L. (2018).
Inhibition of histone deacetylase 6 (HDAC6) protects against vincristine-induced peripheral neuropathies and inhibits tumor growth. Neurobiology of Disease, 111, Art.No. S0969-9961(17)30267-X, 59-69. Van Helleputte, L., Kater, M., Cook, D.P., Eykens, C., Rossaert, E., Haeck, W., Jaspers, T., Geens, N., Vanden Berghe, P., Gysemans, C., Mathieu, C., Robberecht, W., Van Damme, P., Cavaletti, G., Jarpe, M., Van Den Bosch, L. (2018).
Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition. bioRxiv Dittlau, K.S., Krasnow, E., Fumagalli, L., Vandoorne, T., Baatsen, P., Kerstens, A., Giacomazzi, G., Pavie, B., Sampaolesi, M., Van Damme, P., Van Den Bosch, L. (2020).
HDAC6 inhibition restores TDP-43 pathology and axonal transport defects in human motor neurons with TARDBP mutations. EMBO JOURNAL, 40 (7), Art.No. ARTN e106177. doi: 10.15252/embj.2020106177 Open Access. Fazal, R., Boeynaems, S., Swijsen, A., De Decker, M., Fumagalli, L., Moisse, M., Vanneste, J., Guo, W., Boon, R., Vercruysse, T., Eggermont, K., Swinnen, B., Beckers, J., Pakravan, D., Vandoorne, T., Vanden Berghe, P., Verfaillie, C., Van den Bosch, L., Van Damme, P. with Van den Bosch, L. (corresp. author), Van Damme, P. (corresp. author) (2021).
FUS-ALS hiPSC-derived astrocytes impair human motor units through both gain-of-toxicity and loss-of-support mechanisms. Katarina Stoklund Dittlau, Lisanne Terrie, Pieter Baatsen,4 Axelle Kerstens, Lim De Swert, Rekin’s Janky, Nikky Corthout, Pegah Masrori, Philip Van Damme, Poul Hyttel, Morten Meyer, Lieven Thorrez, Kristine Freude and Van Den Bosch Ludo.(2023)