Bernhard Landwehrmeyer

Georg Bernhard Landwehrmeyer FRCP is a German neurologist and neuroscientist in the field of neurodegeneration primarily focusing on Huntington's disease.[1] Landwehrmeyer is a professor of neurology at Ulm University Hospital. He was one of the founders of the European Huntington's Disease Network (EHDN) in 2004 and was chairman of its executive committee until 2014.[1]

Bernhard Landwehrmeyer

Landwehrmeyer in 2022
Born
Georg Bernhard Landwehrmeyer

1960 (age 6263)
Freiburg, Germany
Alma mater
Known forResearch into neurodegeneration, particularly Huntington disease
Scientific career
Fields
InstitutionsUKU
Thesis (1990)
Doctoral advisorR. Jung
Websitewww.uniklinik-ulm.de/neurologie/sprechstunden-ambulanzen/morbus-huntington.html

Education and career

Landwehrmeyer received his MD degree and Doctoral Degree from the Albert Ludwigs University of Freiburg, Germany, where he also completed a residency in neurology, research training in neuropathology and molecular pharmacology, and a residency in neurology and psychiatry.[1][2] Landwehrmeyer studied at the Royal Victoria Hospital, Belfast and Kantonsspital St. Gallen, Basel. He was a post-Doc from 1993 to 1995 at Massachusetts General Hospital, Harvard Medical School. During 1995–1999, he was a staff member at Albert Ludwigs University of Freiburg, Department of Neurology & Psychiatry. In 1999, he received his Board certification in Neurology and has been a full professor since 2000.[3] He served as principal investigator in numerous HD clinical trials[4][5][6] and observational studies[7][8] and is the principal investigator of the CHDI-sponsored Enroll-HD study.[3]

Research

Landwehrmeyer started working on Huntington's Disease (HD) in 1993 when he started a postdoc at Massachusetts General Hospital (MGH) with Anne B. Young, then Chief of Neurology, a couple of months before the HD gene and the HD expansion mutation was discovered. He went to Venezuela with Anne and Nancy Wexler several times, and was alerted to stimulating HD field studies aside from work at the bench.[9]

In 2000 he was appointed full Professor of Neurology, 'Clinical Neurobiology,' at the University of Ulm and was given the opportunity to organize (together with Albert Ludolph, the chairperson of the Department of Neurology at the University of Ulm, who initiated the work) the first large (>500 participants), long-term (3-year randomized clinical trial, followed by a blinded extension) multicenter European phase III HD trial. This collaboration led to forming the European HD Network (EHDN) in 2003–2004, funded by CHDI Foundation, a philanthropic US-American organization. He is the founding chair of the executive committee of EHDN and served in this capacity in 2004–2014.[10] He continues to serve as leader of the EHDN project at the University of Ulm.[11]

The large prospective observational cohort study REGISTRY,[7] conducted by EHDN, recruiting more than 15,000 participants, merged with the cohort study of the Huntington Study Group (HSG) to form Enroll-HD study[8] in 2011, which is still ongoing. Landwehrmeyer serves as the Principal Investigator (PI) of Enroll-HD, a worldwide platform to facilitate HD research and to conduct prospective, observational HD cohort studies for HD families.[8]

His main area of interest is neurodegenerative diseases, such as Huntington disease,[12][13][14] Parkinsonian disorders (including progressive supranuclear palsy[15] and multiple system atrophy),[16] frontotemporal lobar degeneration (FTD),[17][18][19] and amyotrophic lateral sclerosis[20][21][22] (ALS). Other topics on which he published include neuroimaging[23][24] and pain.[25][26] Vast majority of Landwehrmeyer's publications are devoted to various aspects of neurobiology of HD,[27][28] including its genetics,[29][9] genetic modifiers.[30]

Bernhard Landwehrmeyer was involved in almost all RCTs in HD conducted in Europe since 1999, often serving as coordinating PI or national lead investigator. He contributed to Track-HD[31] and Track-ON HD,[32] two influential observational studies in HD, and to 26 phase I-III clinical trials, primarily in HD,[33][34][35] including a first-in-man intrathecal application of antisense oligonucleotides ASO to silence huntingtin gene expression evaluating the safety, tolerability, and efficacy of intrathecally administered agents[36] as well as non-pharmacological interventions, studying the impact of physical activity and exercise in people with HD.

Landwehrmeyer directs the HD Center Ulm, where a multi-disciplinary team takes care of over 700 with HD in an out-patient setting where more than 600 agreed to participate in Enroll-HD. This multi-disciplinary center provides genetic counselling, clinical in- and out-patient services as well as rehabilitation for HD affected families along with basic and translational science. In addition, the HD Center South (in Taufkirchen/Vils) offers 19 in-patient beds dedicated to HD in the setting of a psychiatric hospital and 20-25 beds for in-patient rehab at Ulm.

Landwehrmeyer's most significant publications are:

  • Long, Jeffrey D; Mills, James A; Leavitt, Blair R; Durr, Alexandra; Roos, Raymund A; Stout, Julie C; Reilmann, Ralf; Landwehrmeyer, Bernhard (2017). "Survival End Points for Huntington Disease Trials Prior to a Motor Diagnosis". JAMA Neurol. 74 (11): 1352–1360. doi:10.1001/jamaneurol.2017.2107. PMC 5710578. PMID 28975278.
  • Lehmer, Carina; Oeckl, Patrick; Weishaupt, Jochen H; Volk, Alexander E; Diehl-Schmid, Janine; Schroeter, Matthias L; Lauer, Martin; Kornhuber, Johannes; Levin, Johannes; Fassbender, Klaus; Landwehrmeyer, Bernhard (2017). "Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD". EMBO Mol Med. 9 (7): 859–868. doi:10.15252/emmm.201607486. PMC 5494528. PMID 28408402.
  • Tabrizi, Sarah J; Scahill, Rachael I; Owen, Gail; Durr, Alexandra; Leavitt, Blair R; Roos, Raymund A; Borowsky, Beth; Landwehrmeyer, Bernhard (2013). "Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: analysis of 36-month observational data". Lancet Neurol. 12 (7): 673–49. doi:10.1016/S1474-4422(13)70088-7. PMID 23664844. S2CID 12204298.

Landwehrmeyer is a Fellow of the Royal College of Physicians and a member of several learned medical societies.

As of April 2022, Landwehrmeyer had authored over 300 publications, with over 15,000 citations for his research.[37]

Research awards

Personal life

Landwehrmeyer currently lives in Ulm, Germany. His father, Richard Landwehrmeyer, was a German librarian. From 1972 to 1987 he headed the University Library of Tübingen[44] and from 1987 to 1995 the State Library of Berlin as Director General.

References

  1. Landwehrmeyer, G Bernhard (2012). "Interview: Following a standard of care for Huntington's disease". Neurodegener Dis Manag. 2 (2): 159–63. doi:10.2217/nmt.12.3.
  2. Deeprose, Catherine (2 July 2021). "Taking Stock: Interview with G. Bernhard Landwehrmeyer" (PDF). EHDN News. No. 43. Retrieved 30 April 2022.
  3. "Executive Committee - Public Documents". European Huntington's Disease Network. Retrieved 30 April 2022.
  4. "An Exploratory Clinical Trial in Early Stage Huntington's Disease Patients With SEN0014196 (PADDINGTON)". ClinicalTrials.gov. United States National Library of Medicine. 24 November 2015. Retrieved 1 May 2022. ... Principal Investigator: Bernhard G Landwehrmeyer, MD, PhD European Huntington's Disease Network ...'
  5. "Imaging of PDE10A Enzyme Levels in Huntington's Disease Gene Expansion Carriers and Healthy Controls With PET. (PEARL-HD)". ClinicalTrials.gov. United States National Library of Medicine. 31 May 2016. Retrieved 1 May 2022. ... Principal Investigator: Bernhard Landwehrmeyer, MD, PhD Ulm University Hospital ...'
  6. "Effects of Pregabalin on Mechanical Hyperalgesia". ClinicalTrials.gov. United States National Library of Medicine. 4 April 2007. Retrieved 1 May 2022.
  7. "REGISTRY - an Observational Study of the European Huntington's Disease Network (EHDN)". ClinicalTrials.gov. United States National Library of Medicine. 14 September 2017. Retrieved 1 May 2022. ... Principal Investigator: Bernhard Landwehrmeyer, Professor University Hospital of Ulm / Dept. of Neurology ...'
  8. "Enroll -HD: A Prospective Registry Study in a Global Huntington's Disease Cohort". ClinicalTrials.gov. United States National Library of Medicine. 29 March 2022. Retrieved 1 May 2022. ... Principal Investigator: Bernhard G Landwehrmeyer, MD, PhD University of Ulm ...'
  9. Landwehrmeyer, G. Bernhard; McNeil, Sandra M.; Dure, Leon S. IV; Ge, Pei; Aizawa, Hitoshi; Huang, Qin; Ambrose, Christine M.; Duyao, Mabel P.; Bird, Edward D.; Bonilla, Ernesto; Young, Margot de; Avila-Gonzales, Alejandro J.; Wexler, Nancy S.; DiFiglia, Marian; Gusella, James F.; MacDonald, Marcy E.; Penney, John B.; Young, Anne B.; Vonsattel, Jean-Paul (1995). "Huntington's disease gene: regional and cellular expression in brain of normal and affected individuals". Ann Neurol. 37 (2): 218–30. doi:10.1002/ana.410370213. PMID 7847863. S2CID 40930776.
  10. Townhill, Jenny; McLean, Tim; Levey, Jamie; Rosser, Anne; Weydt, Patrick; Orth, Michael; Capper-Loup, Christine (2021). "F46 The European huntington's disease network". Journal of Neurology, Neurosurgery, and Psychiatry. 92 (1): 218–30. doi:10.1136/jnnp-2021-EHDN.89. S2CID 239647435.
  11. "Das Team der Morbus Huntington Sprechstunde". Universitätsklinikum Ulm (in German). Retrieved 2 May 2022.
  12. van der Burg, Jorien M M; Gardiner, Sarah L; Ludolph, Albert C; Landwehrmeyer, G Bernhard (2017). "Body weight is a robust predictor of clinical progression in Huntington disease". Ann Neurol. 82 (3): 479–483. doi:10.1002/ana.25007. PMID 28779551. S2CID 20730952.
  13. Langbehn, Douglas R; Stout, Julie C; Gregory, Sarah; Mills, James A; Durr, Alexandra; Leavitt, Blair R; Roos, Raymund A C; Long, Jeffrey D; Owen, Gail; Johnson, Hans J; Borowsky, Beth; Craufurd, David; Reilmann, Ralf; Landwehrmeyer, G Bernhard (2019). "Association of CAG Repeats With Long-term Progression in Huntington Disease". JAMA Neurol. 76 (11): 1375–1385. doi:10.1001/jamaneurol.2019.2368. PMC 6692683. PMID 31403680.
  14. Lunkes, Astrid; Lindenberg, Katrin S; Ben-Haı̈em, Léa; Weber, Chantal; Devys, Didier; Landwehrmeyer, G Bernhard; Mandel, Jean-Louis; Trottier, Yvon (2002). "Proteases Acting on Mutant Huntingtin Generate Cleaved Products that Differentially Build Up Cytoplasmic and Nuclear Inclusions". Molecular Cell. 10 (2): 259–269. doi:10.1016/S1097-2765(02)00602-0. PMID 12191472.
  15. Brown, Richard G; Lacomblez, Lucette; Landwehrmeyer, Bernard G (2010). "Cognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy". Brain. 133 (8): 2382–2393. doi:10.1093/brain/awq158. PMID 20576697.
  16. Süssmuth, Sigurd D; Uttner, Ingo; Landwehrmeyer, Bernhard; Pinkhardt, Elmar H; Brettschneider, Johannes; Petzold, Axel; Kramer, Bernd; Schulz, Jörg B; Palm, Christian; Otto, Markus; Ludolph, Albert C; Kassubek, Jan; Tumani, Hayrettin (2010). "Differential pattern of brain-specific CSF proteins tau and amyloid-beta in Parkinsonian syndromes". Mov Disord. 25 (9): 1284–8. doi:10.1002/mds.22895. PMID 20589870. S2CID 40634639.
  17. Otto, M; Ludolph, A C; Landwehrmeyer, B; Förstl, H; Diehl-Schmid, J; Neumann, M; Kretzschmar, H A; Schroeter, M; Kornhuber, J; Danek, A; FTLD consortium (2011). "Konsortium zur Erforschung der frontotemporalen Lobärdegeneration". Der Nervenarzt (in German). 82 (1002): 1002–1005. doi:10.1007/s00115-011-3261-3. PMID 21805118.
  18. Frings, Lars; Mader, Irina; Landwehrmeyer, G Bernhard; Weiller, Cornelius; Hüll, Michael; Huppertz, Hans-Jürgen (2011). "Quantifying change in individual subjects affected by frontotemporal lobar degeneration using automated longitudinal MRI volumetry". Hum Brain Mapp. 33 (7): 1526–35. doi:10.1002/hbm.21304. PMC 6869947. PMID 21618662.
  19. Denk, Johannes; Oberhauser, Felix; Kornhuber, Johannes; Wiltfang, Jens; Fassbender, Klaus; Schroeter, Matthias L; Volk, Alexander E; Diehl-Schmid, Janine; Prudlo, Johannes; Danek, Adrian; Landwehrmeyer, Bernhard; Lauer, Martin; Otto, Markus; Jahn, Holger (2018). "Specific serum and CSF microRNA profiles distinguish sporadic behavioural variant of frontotemporal dementia compared with Alzheimer patients and cognitively healthy controls". PLOS ONE. 13 (5): e0197329. Bibcode:2018PLoSO..1397329D. doi:10.1371/journal.pone.0197329. PMC 5945001. PMID 29746584.
  20. Münch, C; Ebstein, M; Seefried, U; Zhu, B; Stamm, S; Landwehrmeyer, G B; Ludolph, A C; Schwalenstöcker, B; Meyer, T (2002). "Alternative splicing of the 5′-sequences of the mouse EAAT2 glutamate transporter and expression in a transgenic model for amyotrophic lateral sclerosis". J Neurochem. 82 (3): 594–603. doi:10.1046/j.1471-4159.2002.01012.x. PMID 12153483. S2CID 26006717.
  21. Steinacker, Petra; Verde, Federico; Fang, Lubin; Feneberg, Emily; Oeckl, Patrick; Roeber, Sigrun; Anderl-Straub, Sarah; Danek, Adrian; Diehl-Schmid, Janine; Fassbender, Klaus; Fliessbach, Klaus; Foerstl, Hans; Giese, Armin; Jahn, Holger; Kassubek, Jan; Kornhuber, Johannes; Landwehrmeyer, G Bernhard (2002). "Chitotriosidase (CHIT1) is increased in microglia and macrophages in spinal cord of amyotrophic lateral sclerosis and cerebrospinal fluid levels correlate with disease severity and progression". Journal of Neurology, Neurosurgery, and Psychiatry. 89 (3): 239–247. doi:10.1136/jnnp-2017-317138. PMID 29142138. S2CID 3411700.
  22. van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M (2016). "Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis". Nat Genet. 48 (9): 1043–1048. doi:10.1038/ng.3622. PMC 5556360. PMID 27455348. ...  Department of Neurology, Ulm University, Ulm, Germany: Bernhard Landwehrmeyer, Albert C Ludolph, Jochen H Weishaupt & Peter M Andersen ...'
  23. Fazio, Patrik; Schain, Martin; Mrzljak, Ladislav; Amini, Nahid; Nag, Sangram; Al-Tawil, Nabil; Fitzer-Attas, Cheryl J; Bronzova, Juliana; Landwehrmeyer, Bernhard; Sampaio, Cristina; Halldin, Christer; Varrone, Andrea (2017). "Patterns of age related changes for phosphodiesterase type-10A in comparison with dopamine D2/3 receptors and sub-cortical volumes in the human basal ganglia: A PET study with 18F-MNI-659 and 11C-raclopride with correction for partial volume effect". NeuroImage. 152 (4): 330–339. doi:10.1002/mds.10229. PMID 12210870. S2CID 32410300.
  24. Wolf, Robert C; Grön, Georg; Sambataro, Fabio; Vasic, Nenad; Wolf, Nadine D; Thomann, Philipp A; Saft, Carsten; Landwehrmeyer, G Bernhard; Orth, Michael (2011). "Magnetic resonance perfusion imaging of resting-state cerebral blood flow in preclinical Huntington's disease". J Cereb Blood Flow Metab. 31 (9): 1908–18. doi:10.1038/jcbfm.2011.60. PMC 3185882. PMID 21559028.
  25. Maier, C; Baron, R; Tölle, T R; Binder, A; Birbaumer, N; Birklein, F; Gierthmühlen, J; Flor, H; Geber, C; Huge, V; Krumova, E K; Landwehrmeyer, G B; Magerl, W; Maihöfner, C; Richter, H; Rolke, R; Scherens, A; Schwarz, A; Sommer, C; Tronnier, V l; Üçeyler, N; Valet, M; Wasner, G; Treede, D-R (2010). "Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values". Pain. 150 (3): 439–450. doi:10.1016/j.pain.2010.05.002. PMID 20627413. S2CID 9601884.
  26. Rolke, R; Baron, R; Maier, C; Tölle, T R; Treede, D R; Beyer, A; Binder, A; Birbaumer, N; Birklein, F; Bötefür, I C; Braune, S; Flor, H; Huge, V; Klug, R; Landwehrmeyer, G B; Magerl, W; Maihöfner, C; Rolko, C; Schaub, C; Scherens, A; Sprenger, T; Valet, M; Wasserka, B (2006). "Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes". Pain. 123 (3): 231–243. doi:10.1016/j.pain.2006.01.041. PMID 16697110. S2CID 44333.
  27. McAllister, Branduff; Donaldson, Jasmine; Binda, Caroline S (2022). "Exome sequencing of individuals with Huntington's disease implicates FAN1 nuclease activity in slowing CAG expansion and disease onset". Nat Neurosci. 25 (4): 446–457. doi:10.1038/s41593-022-01033-5. PMC 8986535. PMID 35379994. ...  Department of Neurology, Ulm University, Ulm, Germany: Bernhard Landwehrmeyer ...'
  28. Goehler, Heike; Lalowski, Maciej; Stelzl, Ulrich; Waelter, Stephanie; Stroedicke, Martin; Worm, Uwe; Droege, Anja; Lindenberg, Katrin S; Knoblich, Maria; Haenig, Christian; Herbst, Martin; Suopanki, Jaana; Scherzinger, Eberhard; Abraham, Claudia; Bauer, Bianca; Hasenbank, Renate; Fritzsche, Anja; Ludewig, Andreas H; Buessow, Konrad; Coleman, Sarah H; Gutekunst, Claire-Anne; Landwehrmeyer, G Bernhard (2004). "A Protein Interaction Network Links GIT1, an Enhancer of Huntingtin Aggregation, to Huntington's Disease". Molecular Cell. 15 (6): 853–865. doi:10.1016/j.molcel.2004.09.016. PMID 15383276.
  29. Genetic Modifiers of Huntington's Disease (GeM-HD) Consortium (2019). "CAG Repeat Not Polyglutamine Length Determines Timing of Huntington's Disease Onset". Cell. 178 (4): 887–900. doi:10.1016/j.cell.2019.06.036. PMC 6700281. PMID 31398342. ... Consortia <…> Group 5: Michael Orth and G. Bernhard Landwehrmeyer on behalf of the European Huntington's Disease Network (EHDN) Registry investigators; Jane S. Paulsen on behalf of the Huntington Study Group (HSG) PREDICT-HD investigators ...
  30. Genetic Modifiers of Huntington's Disease (GeM-HD) Consortium (2015). "Identification of Genetic Factors that Modify Clinical Onset of Huntington's Disease". Cell. 162 (3): 516–526. doi:10.1016/j.cell.2015.07.003. PMC 4524551. PMID 26232222.
  31. Tabrizi, Sarah J; Reilmann, Ralf; Roos, Raymund A C; Durr, Alexandra; Leavitt, Blair; Owen, Gail; Jones, Rebecca; Johnson, Hans; Craufurd, David; Hicks, Stephen L; Kennard, Christopher; Landwehrmeyer, Bernhard; Stout, Julie C; Borowsky, Beth; Scahill, Rachael I; Frost, Chris; Langbehn, Douglas R; TRACK-HD investigators (2012). "Potential endpoints for clinical trials in premanifest and early Huntington's disease in the TRACK-HD study: analysis of 24 month observational data". Lancet Neurol. 11 (1): 42–53. doi:10.1016/S1474-4422(11)70263-0. PMID 22137354. S2CID 34929053.
  32. Klöppel, Stefan; Gregory, Sarah; Scheller, Elisa; Minkova, Lora; Razi, Adeel; Durr, Alexandra; Roos, Raymund A C; Leavitt, Blair R; Papoutsi, Marina; Landwehrmeyer, G Bernhard; Reilmann, Ralf; Borowsky, Beth; Johnson, Hans; Mills, James A; Owen, Gail; Stout, Julie; Scahill, Rachael I; Long, Jeffrey D; Rees, Geraint; Tabrizi, Sarah J; Track-On investigators (2015). "Compensation in Preclinical Huntington's Disease: Evidence From the Track-On HD Study". eBioMedicine. 2 (10): 1420–9. doi:10.1016/j.ebiom.2015.08.002. PMC 4634199. PMID 26629536.
  33. HORIZON Investigators of the Huntington Study Group and European Huntington's Disease Network (2013). "A Randomized, Double-blind, Placebo-Controlled Study of Latrepirdine in Patients With Mild to Moderate Huntington Disease". JAMA Neurol. 70 (1): 25–33. doi:10.1001/2013.jamaneurol.382. PMID 23108692. S2CID 21645327. ... *The authors for the HORIZON Investigators of the Huntington Study Group and European Huntington's Disease Network are as follows: <…> Georg B. Landwehrmeyer ...
  34. Reilmann, Ralf; McGarry, Andrew; Grachev, Igor D; Savola, Juha-Matti; Borowsky, Beth; Eyal, Eli; Gross, Nicholas; Langbehn, Douglas; Schubert, Robin; Wickenberg, Anna Teige; Papapetropoulos, Spyros; Hayden, Michael; Squitieri, Ferdinando; Kieburtz, Karl; Landwehrmeyer, G Bernhard (2019). "Safety and efficacy of pridopidine in patients with Huntington's disease (PRIDE-HD): a phase 2, randomised, placebo-controlled, multicentre, dose-ranging study". Lancet Neurol. 18 (2): 165–176. doi:10.1016/S1474-4422(18)30391-0. PMID 30563778. S2CID 54588998.
  35. Landwehrmeyer, G. Bernhard; Dubois, Bruno; de Yébenes, Justo Garcia (2007). "Riluzole in Huntington's disease: a 3-year, randomized controlled study". Ann Neurol. 62 (3): 161–272. doi:10.1002/ana.21181. PMID 17702031. S2CID 23715098.
  36. Tabrizi, Sarah J; Leavitt, Blair R; Landwehrmeyer, G Bernhard (2019). "Targeting Huntingtin Expression in Patients with Huntington's Disease". N Engl J Med. 680 (24): 2307–2316. doi:10.1056/NEJMoa1900907. PMID 31059641. S2CID 146811503.
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  40. "Pharmacodynamic Approaches to Demonstration of Disease-Modification in Huntington's Disease by SEN0014196". CORDIS. European Commission. Retrieved 30 April 2022.
  41. "CHDI Foundation". CHDI Foundation. CHDI Foundation. Retrieved 30 April 2022.
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  44. "History of the library". University Library of Tübingen. University of Tübingen. Retrieved 1 May 2022. ... 1972-1987: Richard Landwehrmeyer ...'
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