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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 (ENCCALS)

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 (570)

Validating biomarkers and models for epigenetic inference of alcohol consumption from blood

Maas Silvana C E, Vidaki Athina, Teumer Alexander, Costeira Ricardo, Wilson Rory, van Dongen Jenny, Beekman Marian, Völker Uwe, Grabe Hans J, Kunze Sonja, Ladwig Karl-Heinz, van Meurs Joyce B J, Uitterlinden André G, Voortman Trudy, Boomsma Dorret I, Slagboom P Eline, van Heemst Diana, van der Kallen Carla J H, van den Berg Leonard H, Waldenberger Melanie, Völzke Henry, Peters Annette, Bell Jordana T, Ikram M Arfan, Ghanbari Mohsen, Kayser Manfred 26 okt 2021, In: Clinical Epigenetics. 13

Safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis (the REFALS study):a randomised, double-blind, placebo-controlled phase 3 trial

Cudkowicz Merit, Genge Angela, Maragakis Nicholas, Petri Susanne, van den Berg Leonard, Aho Valtteri V, Sarapohja Toni, Kuoppamäki Mikko, Garratt Chris, Al-Chalabi Ammar, okt 2021, In: The Lancet. Neurology. 20 , p. 821-831 11 p.

A Road Map for Remote Digital Health Technology for Motor Neuron Disease

van Eijk Ruben P A, Beelen Anita, Kruitwagen Esther T, Murray Deirdre, Radakovic Ratko, Hobson Esther, Knox Liam, Helleman Jochem, Burke Tom, Rubio Pérez Miguel Ángel, Reviers Evy, Genge Angela, Steyn Frederik J, Ngo Shyuan, Eaglesham John, Roes Kit C B, van den Berg Leonard H, Hardiman Orla, McDermott Christopher J 22 sep 2021, In: Journal of Medical Internet Research. 23

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Johnson Janel O, Chia Ruth, Miller Danny E, Li Rachel, Kumaran Ravindran, Abramzon Yevgeniya, Alahmady Nada, Renton Alan E, Topp Simon D, Gibbs J Raphael, Cookson Mark R, Sabir Marya S, Dalgard Clifton L, Troakes Claire, Jones Ashley R, Shatunov Aleksey, Iacoangeli Alfredo, Al Khleifat Ahmad, Ticozzi Nicola, Silani Vincenzo, Gellera Cinzia, Blair Ian P, Dobson-Stone Carol, Kwok John B, Bonkowski Emily S, Palvadeau Robin, Tienari Pentti J, Morrison Karen E, Shaw Pamela J, Al-Chalabi Ammar, Brown Robert H, Calvo Andrea, Mora Gabriele, Al-Saif Hind, Gotkine Marc, Leigh Fawn, Chang Irene J, Perlman Seth J, Glass Ian, Scott Anna I, Shaw Christopher E, Basak A Nazli, Landers John E, Chiò Adriano, Crawford Thomas O, Kenna Kevin P, McLaughlin Russell L, van Rheenen Wouter, Veldink Jan H, van den Berg Leonard H, 30 aug 2021, In: JAMA Neurology. 78 , p. 1236-1248 13 p.

Informal Caregivers in Amyotrophic Lateral Sclerosis:A Multi-Centre, Exploratory Study of Burden and Difficulties

Conroy Éilís, Kennedy Polly, Heverin Mark, Leroi Iracema, Mayberry Emily, Beelen Anita, Stavroulakis Theocharis, van den Berg Leonard H, McDermott Christopher J, Hardiman Orla, Galvin Miriam 20 aug 2021, In: Brain sciences. 11 , p. 1-16

High-resolution mapping identifies HLA class II associations with multifocal motor neuropathy

Bos Jeroen W., Otten Henny G., Herraets Ingrid J.T., Goedee H. Stephan, Cats E. A., de Hoop Talitha, Verduijn Willem, van der Pol W. Ludo, van den Berg Leonard H. mei 2021, In: Neurobiology of Aging. 101 , p. 79-84 6 p.

The Effect of SMN Gene Dosage on ALS Risk and Disease Severity

Moisse Matthieu, Zwamborn Ramona A J, van Vugt Joke, van der Spek Rick, van Rheenen Wouter, Kenna Brendan, Van Eijk Kristel, Kenna Kevin, Corcia Philippe, Couratier Philippe, Vourc'h Patrick, Hardiman Orla, McLaughin Russell, Gotkine Marc, Drory Vivian, Ticozzi Nicola, Silani Vincenzo, de Carvalho Mamede, Mora Pardina Jesús S, Povedano Monica, Andersen Peter M, Weber Markus, Başak Nazli A, Chen Xiao, Eberle Michael A, Al-Chalabi Ammar, Shaw Chris, Shaw Pamela J, Morrison Karen E, Landers John E, Glass Jonathan D, Robberecht Wim, van Es Michael, van den Berg Leonard, Veldink Jan, Van Damme Philip, apr 2021, In: Annals of Neurology. 89 , p. 686-697 12 p.

Participation and autonomy in the first 10 months after diagnosis of ALS: a longitudinal study.

Kruitwagen-van Reenen Esther, van den Berg Leonard, Visser-Meilij JM Anne, Post Marcel, Scholten Eline, van Groenestijn AC 8 mrt 2021, In: Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration. 22 , p. 459-466 8 p.

SCFD1 expression quantitative trait loci in amyotrophic lateral sclerosis are differentially expressed

Iacoangeli Alfredo, Fogh Isabella, Selvackadunco Sashika, Topp Simon D, Shatunov Aleksey, van Rheenen Wouter, Al-Khleifat Ahmad, Opie-Martin Sarah, Ratti Antonia, Calvo Andrea, Van Damme Philip, Robberecht Wim, Chio Adriano, Dobson Richard J, Hardiman Orla, Shaw Christopher E, van den Berg Leonard H, Andersen Peter M, Smith Bradley N, Silani Vincenzo, Veldink Jan H, Breen Gerome, Troakes Claire, Al-Chalabi Ammar, Jones Ashley R, 2021, In: Brain communications. 3

Discussing personalized prognosis in amyotrophic lateral sclerosis:development of a communication guide

van Eenennaam Remko M, Kruithof Willeke J, van Es Michael A, Kruitwagen-van Reenen Esther T, Westeneng Henk-Jan, Visser-Meily Johanna M A, van den Berg Leonard H, Beelen Anita 14 dec 2020, In: BMC Neurology. 20 , p. 1-11

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