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prof. dr. L.H. (Leonard) van den Berg

prof. dr. L.H. (Leonard) van den Berg

Full Professor
prof. dr. L.H. (Leonard) van den Berg
  • Neurologen
  • Neurology & Neurosurgery

Biography

Biography

Leonard van den Berg did a fellowship at the Neurological Institute at Columbia University in New York and obtained his PhD degree in 1995 in Utrecht. He has been professor of Experimental Neurology since 2005 and leads a research group focused on translational research into ALS and other diseases of motor neurons. His research has been focused on the search for effective treatment for patients with motor neuron diseases and motor neuropathies by delineating the biological and molecular pathways that initiate and/or drive motor neuron degeneration. These efforts are based on clinical, lifestyle, environmental,genetic and imaging data obtained from large population-based case–control studies. Part of the research activity has been focused on characterizing the phenotype, diagnosis, pathology and treatment options for multifocal motor neuropathy, which is an important treatable ALS mimic. He is principal investigator of the largest, prospective population-based case-control study in ALS (PAN) to provide class I level of evidence of both environmental/lifestyle and genetic factors that determine risk and outcome of ALS and related motor neuron disorders. His research group has strong bioinformatic expertise in genome-wide association studies, copy number variation, gene expression pathways and other systems biology approaches. He is founder and director of The Netherlands ALS Center, which aims to improve the diagnosis, treatment/care and scientific research for ALS in The Netherlands. He promotes international collaborations on ALS research as chairman of the European Network to find the Cure for ALS (ENCALS)) and as coordinator of awarded EU grants (FP7 Euro-MOTOR (systems biology), JPND SOPHIA (biomarkers)).He promotes international collaborations on ALS research as chairman of the European Network for the Cure of ALS (ENCALS)), as coordinator of awarded EU grants (FP7 Euro-MOTOR(systems biology), JPND SOPHIA (biomarkers)) and as initiator of the worldwide ALS genetics research Project MinE.

Prof. Leonard van den Berg has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits.

UMCU has received major funding by Julius Clinical for participating in clinical studies sponsored by Amylyx and Ferrer.

UMCU has received funding by Apellis and Orphazyme for providing outcome measure training during clinical trials.

UMCU received minor funding (€200-10,000 per industrial partner) for consultation and invited lectures by Neuropath, Orphazyme, Avexis, BrainEver, Amylyx, Argenx, Calico Life Sciences, Ferrer, Biogen, QurAlis, Brainstorm Cell Therapeutics, Arrowhead, Egeen, Corcept, Sanofi, Kadimastem, Medscape, Takeda, Ionis, RRD, Uniqure and Novartis.

UMC Utrecht participation in following clinical trials (all payments are received by the UMC Utrecht)

UMC Utrecht executes the investigator initiated study: Safety and Efficacy of Tauroursodeoxycholic (TUDCA) as add-on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis (ALS). Van den Berg is local principal investigator. The UMC Utrecht sponsors this trial (2019-)

UMC Utrecht executes the industry initiated study: An Extension Study to Assess the Long-Term Safety, Tolerability, Pharmacokinetics, and Effect on Disease Progression of BIIB078 Administered to Previously Treated Adults With C9ORF72-Associated Amyotrophic Lateral Sclerosis. Van den Berg is local principal investigator. (2020-)

UMC Utrecht executes the industry initiated study: A Phase 1 Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB105 Administered Intrathecally to Adults With Amyotrophic Lateral Sclerosis With or Without Poly-CAG Expansion in the Ataxin-2 Gene. Van den Berg is local principal investigator. (2020-)

UMC Utrecht executes the industry initiated study: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-004 Administered Intrathecally to Patients With C9orf72-associated Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal Dementia (FTD). Van den Berg is local principal investigator. (2021-)

UMC Utrecht executes the industry initiated study: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Assess Efficacy, Long Term Safety and Tolerability of RT001 in Subjects With Amyotrophic Lateral Sclerosis. Van den Berg is local principal investigator. (2021-)

UMC Utrecht executes the industry initiated study: A Multi-arm, Adaptive, Group-sequential trial NETwork to evaluate lithium efficacy in patients with Amyotrophic Lateral Sclerosis (ALS). This trial is sponsored by the UMC Utrecht. Van den Berg is local principal investigator. (2021-) TRICALS and the UMC Utrecht sponsor this trial.

UMC Utrecht executes the industry initiated study: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Subjects With Amyotrophic Lateral Sclerosis (ALS). Van den Berg is local principal investigator. (2021-)

UMC Utrecht executes the industry initiated study: A Phase 1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study, Followed by an Open-Label Extension, to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral Sclerosis. Van den Berg is local principal investigator. (2021-)

UMC Utrecht executes the investigator initiated study study: Targeting Metabolic Flexibility in ALS (MetFlex); Safety and Tolerability of Trimetazidine for the Treatment of ALS. Van den Berg is local principal investigator. The UMC Utrecht sponsors this trial (2021-)

Research line

Neuromuscular Disease, Motor Neuron Disease

Most recent key publications

1: Walhout R, Westeneng HJ, Verstraete E, Hendrikse J, Veldink JH, van den Heuvel MP*, van den Berg LH*. Cortical thickness in ALS: towards a marker for upper motor neuron involvement. J Neurol Neurosurg Psychiatry 2015;86:288-94.
2: Diekstra FP, Van Deerlin VM, van Swieten JC, Al-Chalabi A, Ludolph AC, Weishaupt JH, Hardiman O, Landers JE, Brown RH Jr, van Es MA, Pasterkamp RJ, Koppers M, Andersen PM, Estrada K, Rivadeneira F, Hofman A, Uitterlinden AG, van Damme P, Melki J, Meininger V, Shatunov A, Shaw CE, Leigh PN, Shaw PJ, Morrison KE, Fogh I, Chiò A, Traynor BJ, Czell D, Weber M, Heutink P, de Bakker PI, Silani V, Robberecht W, Veldink JH*, van den Berg LH*. C9orf72 and UNC13A are shared risk loci for amyotrophic lateral sclerosis and frontotemporal dementia: A genome-wide meta-analysis. Ann Neurol 2014;76:120-33.
3: Van den Berg LH. Therapy of amyotrophic lateral sclerosis remains a challenge. Lancet Neurol 2014;13:1062-3
4: Vlam L, van der Pol WL, Cats EA, Straver DC, Piepers S, Franssen H, van den Berg LH. Multifocal motor neuropathy: diagnosis, pathogenesis and treatment strategies. Nature Rev Neurol 2011;8:48-58.
5: Hardiman O, van den Berg LH, Kiernan MC. Clinical diagnosis and management of ALS. Nat Rev Neurol. 2011 Oct 11;7(11):639-49

Side Activities

Chair section Motor Neuron Diseases, European Reference Network - EURO-NMD

Chair Executive Board, European Network for the Cure of ALS (ENCALS)

Chair Executive Board, Treatment Research Initiative to Cure ALS (TRICALS)

Director, Netherlands Neuromuscular Centre

Fellowship and Awards

2015 'Winkler award' from the Dutch Association for Neurology recognizing the largest scientific contribution to neurological science over the past 5 years.
2013 'Forbes Norris award' for high-impact ALS research results in trials, epidemiology and care combined with a major role in the delivery of evidence-based multidisciplinary ALS care.
2011 ‘Sheila Essey Award’ from the American Academy of Neurology (‘This award recognizes an individual who has made significant research contributions in the search for the cause, prevention of, and cure for amyotrophic lateral sclerosis’)
2011-2016 Personal grant ZonMw (VICI ). ‘Amyotrophic lateral sclerosis: disease or syndrome?’
2008-2013 Prinses Beatrix Fonds Neuromuscular Research Prize. ‘The identification and validation of biomarkers for amyotrophic lateral sclerosis’.
2002-2007 Personal grant ZonMw (VIDI subsidie). ‘Genetic susceptibility factors in patients with amyotrophic lateral sclerosis’.
1997-2002 Personal grant (KNAW-onderzoeker). ‘Elucidation of the molecular basis of the cross-reactive immune response to Campylobacter jejuni and peripheral nerve tissue in patients with the Guillain-Barre syndrome using phage antibody display technology’.

Research Output (609)

Acute retigabine-induced effects on myelinated motor axons in amyotrophic lateral sclerosis

Sleutjes Boudewijn T H M, Stikvoort García Diederik J L, Kovalchuk Maria O, Heuberger Jules A A C, Groeneveld Geert Jan, Franssen Hessel, van den Berg Leonard H Aug 2022, In: Pharmacology research & perspectives. 10 , p. 1-7

Author Correction:Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Barc Julien, Tadros Rafik, Glinge Charlotte, Chiang David Y, Jouni Mariam, Simonet Floriane, Jurgens Sean J, Baudic Manon, Nicastro Michele, Potet Franck, Offerhaus Joost A, Walsh Roddy, Choi Seung Hoan, Verkerk Arie O, Mizusawa Yuka, Anys Soraya, Minois Damien, Arnaud Marine, Duchateau Josselin, Wijeyeratne Yanushi D, Muir Alison, Papadakis Michael, Castelletti Silvia, Torchio Margherita, Ortuño Cristina Gil, Lacunza Javier, Giachino Daniela F, Cerrato Natascia, Martins Raphaël P, Campuzano Oscar, Van Dooren Sonia, Thollet Aurélie, Kyndt Florence, Mazzanti Andrea, Clémenty Nicolas, Bisson Arnaud, Corveleyn Anniek, Stallmeyer Birgit, Dittmann Sven, Saenen Johan, Noël Antoine, Honarbakhsh Shohreh, Rudic Boris, Marzak Halim, Rowe Matthew K, Federspiel Claire, Le Page Sophie, Placide Leslie, Veldink Jan H, van den Berg Leonard H, 26 Apr 2022, In: Nature Genetics. 54 , p. 735 1 p.

Whole-genome sequencing reveals that variants in the Interleukin 18 Receptor Accessory Protein 3'UTR protect against ALS

Eitan Chen, Siany Aviad, Barkan Elad, Olender Tsviya, van Eijk Kristel R, Moisse Matthieu, Farhan Sali M K, Danino Yehuda M, Yanowski Eran, Marmor-Kollet Hagai, Rivkin Natalia, Yacovzada Nancy Sarah, Hung Shu-Ting, Cooper-Knock Johnathan, Yu Chien-Hsiung, Louis Cynthia, Masters Seth L, Kenna Kevin P, van der Spek Rick A A, Sproviero William, Al Khleifat Ahmad, Iacoangeli Alfredo, Shatunov Aleksey, Jones Ashley R, Elbaz-Alon Yael, Cohen Yahel, Chapnik Elik, Rothschild Daphna, Weissbrod Omer, Beck Gilad, Ainbinder Elena, Ben-Dor Shifra, Werneburg Sebastian, Schafer Dorothy P, Brown Robert H, Shaw Pamela J, Van Damme Philip, van den Berg Leonard H, Phatnani Hemali, Segal Eran, Ichida Justin K, Al-Chalabi Ammar, Veldink Jan H, Hornstein Eran, Apr 2022, In: Nature Neuroscience. 25 , p. 433-445 13 p.

Genetic variants associated with longitudinal changes in brain structure across the lifespan

Brouwer Rachel M, Klein Marieke, Grasby Katrina L, Schnack Hugo G, Jahanshad Neda, Teeuw Jalmar, Thomopoulos Sophia I, Sprooten Emma, Franz Carol E, Gogtay Nitin, Kremen William S, Panizzon Matthew S, Olde Loohuis Loes M, Whelan Christopher D, Aghajani Moji, Alloza Clara, Alnæs Dag, Artiges Eric, Ayesa-Arriola Rosa, Barker Gareth J, Bastin Mark E, Blok Elisabet, Bøen Erlend, Breukelaar Isabella A, Bright Joanna K, Buimer Elizabeth E L, Bülow Robin, Cannon Dara M, Ciufolini Simone, Crossley Nicolas A, Damatac Christienne G, Dazzan Paola, de Mol Casper L, de Zwarte Sonja M C, Desrivières Sylvane, Díaz-Caneja Covadonga M, Janssen Joost, Koevoets Martijn G J C, Mandl René C W, Setiaman Nikita, van Haren Neeltje E M, Westeneng Henk-Jan, van Eijk Kristel R, Cahn Wiepke, Hillegers Manon, Kahn Rene S, Ophoff Roel A, van den Berg Leonard H, Veldink Jan H, Hulshoff Pol Hilleke E, Apr 2022, In: Nature Neuroscience. 25 , p. 421-432 12 p.

Sports and trauma as risk factors for Motor Neurone Disease:New Zealand case-control study

Chen Grace Xia, Douwes Jeroen, van den Berg Leonard H, Glass Bill, McLean David, 't Mannetje Andrea Martine 31 Mar 2022, In: Acta Neurologica Scandinavica. 145 , p. 770-785 16 p.

Joint modeling of endpoints can be used to answer various research questions in randomized clinical trials

van Eijk Ruben P A, Roes Kit C B, van den Berg Leonard H, Lu Ying 26 Mar 2022, In: Journal of Clinical Epidemiology. 147 , p. 32-39 8 p.

Occupational exposures to pesticides and other chemicals:a New Zealand motor neuron disease case-control study

Chen Grace Xia, Douwes J, van den Berg Leonard, Pearce Neil, Kromhout Hans, Glass Bill, McLean David J, 't Mannetje Andrea Martine 22 Mar 2022, In: Occupational and Environmental Medicine. 79 , p. 412-420 9 p.

Burden and benefit-A mixed methods study of informal Amyotrophic Lateral Sclerosis caregivers in Ireland and the Netherlands

Kennedy Polly, Conroy Éilís, Heverin Mark, Leroi Iracema, Beelen Anita, van den Berg Leonard, Hardiman Orla, Galvin Miriam 14 Mar 2022, In: International Journal of Geriatric Psychiatry. 37 , p. 1-12

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Barc Julien, Tadros Rafik, Glinge Charlotte, Chiang David Y, Jouni Mariam, Simonet Floriane, Jurgens Sean J, Baudic Manon, Nicastro Michele, Potet Franck, Offerhaus Joost A, Walsh Roddy, Choi Seung Hoan, Verkerk Arie O, Mizusawa Yuka, Anys Soraya, Minois Damien, Arnaud Marine, Duchateau Josselin, Wijeyeratne Yanushi D, Muir Alison, Papadakis Michael, Castelletti Silvia, Torchio Margherita, Ortuño Cristina Gil, Lacunza Javier, Giachino Daniela F, Cerrato Natascia, Martins Raphaël P, Campuzano Oscar, Van Dooren Sonia, Thollet Aurélie, Kyndt Florence, Mazzanti Andrea, Clémenty Nicolas, Bisson Arnaud, Corveleyn Anniek, Stallmeyer Birgit, Dittmann Sven, Saenen Johan, Noël Antoine, Honarbakhsh Shohreh, Rudic Boris, Marzak Halim, Rowe Matthew K, Federspiel Claire, Le Page Sophie, Placide Leslie, Veldink Jan H, van den Berg Leonard H, 24 Feb 2022, In: Nature Genetics. 54 , p. 232-239 8 p.

Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS

Hop Paul J, Zwamborn Ramona A J, Hannon Eilis, Shireby Gemma L, Nabais Marta F, Walker Emma M, van Rheenen Wouter, van Vugt Joke J F A, Dekker Annelot M, Westeneng Henk-Jan, Tazelaar Gijs H P, van Eijk Kristel R, Moisse Matthieu, Baird Denis, Al Khleifat Ahmad, Iacoangeli Alfredo, Ticozzi Nicola, Ratti Antonia, Cooper-Knock Jonathan, Morrison Karen E, Shaw Pamela J, Basak A Nazli, Chiò Adriano, Calvo Andrea, Moglia Cristina, Canosa Antonio, Brunetti Maura, Grassano Maurizio, Gotkine Marc, Lerner Yossef, Zabari Michal, Vourc'h Patrick, Corcia Philippe, Couratier Philippe, Mora Pardina Jesus S, Salas Teresa, Dion Patrick, Ross Jay P, Henderson Robert D, van Es Michael A, Pasterkamp R Jeroen, McLaughlin Russell L, Kenna Kevin P, van den Berg Leonard H, Veldink Jan H, Veldink Jan H, van den Berg Leonard H, Deelen Patrick, Deelen Patrick, Veldink Jan H, 23 Feb 2022, In: Science translational medicine. 14 , p. 1-15

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