
Tomas Björklund
Research team manager

Earlier research work
I have over ten-year of experience in the fields of gene therapy, in vivo studies and Parkinson’s disease (PD). My earlier research work has focused on the development of novel AAV (adeno-associated viral) vector based therapies and disease models for PD and related disorders. Two major lines have emerged from that; an optimized therapy for PD using AAV mediated enzyme replacement and novel disease models for PD, Huntington’s disease and dementia with Lewy bodies.
AAV-mediated enzyme replacement has become a very promising clinical candidate that is now being taken by my own company, Genepod Therapeutics, towards clinical trials in Parkinson patients. The disease models we have established using AAV-vectors have started to gain significant momentum and the results have been replicated in a number of labs.
We have recently completed two major studies utilizing a second generation, inhibitory chemogenetic receptor (commonly named DREADDs) in advanced in vivo experiments on cell transplantation for PD where we have for the first time been able to show important mechanisms underlying graft-induced abnormal involuntary movements or dyskinesias (published in Neuron).
Current research work
Translational combination of genome editing and chemogenetic modulation to dissect the striatal circuitry in vivo
The main goal of this project is to validate our newly identified mechanism underlying the emergence of dyskinesias in PD and find a clinically applicable therapeutic approach to modulate this target. In our completed study (Neuron 2016), we have identified the 5-HT6 receptor as a potential therapeutic target in GIDs. In a follow-up study, we have furthered this approach and found mechanistic similarities between the GID and L-DOPA induced dyskinesias (LIDs). Recent studies point to the striatal cholinergic interneurons (AChINs) being a key player in the emergence and maintenance of LIDs in PD and that they can be inhibited through administration of muscarinic receptor antagonists. Using a novel ChAT-Cre transgenic rat in combination with the novel set of AAV-mediated orthogonal DREADDs, we have also shown that AChINs modulate LIDs in PD. In our ongoing work, we seek to bring all these data together and experimentally define a unified model of the Serotonin/Dopamine/Acetylcholine interaction in PD.
Barcode-based genetic screening of novel AAV serotypes for translational gene therapy
We have successfully developed a novel methodology to uniquely label each viral particle in a preparation with a unique identifier sequence (20 nucleotide random sequence) that is inserted in the 3’UTR (untranslated region) of mRNA expressed from the cell infected by that specific particle. Details on this process can be found in our Scientific reports 2016 paper. Using this approach, we have been able to develop an entirely new way to produce, screen and select new AAV serotypes that harbour infectivity profiles that are tailor-made for specific clinical applications.
Publications
Displaying of publications. Sorted by year, then title.
Mutant huntingtin expression in the hypothalamus promotes ventral striatal neuropathology
Rana Soylu Kucharz, Natalie Adlesic, Marcus Davidsson, Tomas Björklund, Maria Björkqvist, et al.
(2023)
PreprintA novel two-factor monosynaptic TRIO tracing method for assessment of circuit integration of hESC-derived dopamine transplants
Patrick Aldrin-Kirk, Malin Åkerblom, Tiago Cardoso, Sara Nolbrant, Andrew F. Adler, et al.
(2022) Stem Cell Reports, 17 p.159-172
Journal articleIn vivo conversion of dopamine neurons in mouse models of Parkinson's disease - a future approach for regenerative therapy?
Malin Parmar, Anders Björklund, Tomas Björklund
(2021) Current Opinion in Genetics & Development, 70 p.76-82
Journal article reviewFRET-Based Screening Identifies p38 MAPK and PKC Inhibition as Targets for Prevention of Seeded α-Synuclein Aggregation
Alexander Svanbergsson, Fredrik Ek, Isak Martinsson, Jordi Rodo, Di Liu, et al.
(2021) Neurotherapeutics, 18 p.1692-1709
Journal articleNext-Generation Gene Therapy for Parkinson's Disease Using Engineered Viral Vectors
Tomas Björklund, Marcus Davidsson
(2021) Journal of Parkinson's Disease, 11 p.209-217
Journal article reviewAAV Production Everywhere : A Simple, Fast, and Reliable Protocol for In-house AAV Vector Production Based on Chloroform Extraction
Matilde Negrini, Gang Wang, Andreas Heuer, Tomas Björklund, Marcus Davidsson
(2020) Current Protocols in Neuroscience, 93 p.103-103
Journal articleA systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism
Marcus Davidsson, Gang Wang, Patrick Aldrin-Kirk, Tiago Cardoso, Sara Nolbrant, et al.
(2019) Proceedings of the National Academy of Sciences of the United States of America, 116 p.27053-27062
Journal articleSeeding of protein aggregation causes cognitive impairment in rat model of cortical synucleinopathy
Elena Espa, Erik K.H. Clemensson, Kelvin C. Luk, Andreas Heuer, Tomas Björklund, et al.
(2019) Movement Disorders, 34 p.1699-1710
Journal articleVector-mediated l-3,4-dihydroxyphenylalanine delivery reverses motor impairments in a primate model of Parkinson's disease
Carl Rosenblad, Qin Li, Elsa Y Pioli, Sandra Dovero, André S L M Antunes, et al.
(2019) Brain : a journal of neurology , p.2402-2416
Journal articlePractical Considerations for the Use of DREADD and Other Chemogenetic Receptors to Regulate Neuronal Activity in the Mammalian Brain
Patrick Aldrin-Kirk, Tomas Björklund
(2019) Methods in molecular biology (Clifton, N.J.), 1937 p.59-87
Journal articleA novel adeno-associated virus capsid with enhanced neurotropism corrects a lysosomal transmembrane enzyme deficiency
Julie Tordo, Claire O'Leary, André S.L.M. Antunes, Nuria Palomar, Patrick Aldrin-Kirk, et al.
(2018) Brain, 141 p.2014-2031
Journal articleMolecular barcoding of viral vectors enables mapping and optimization of mRNA trans-splicing
Marcus Davidsson, Paula Díaz-Fernández, Marcos Torroba, Oliver D. Schwich, Patrick Aldrin-Kirk, et al.
(2018) RNA, 24 p.673-687
Journal articleChemogenetic modulation of cholinergic interneurons reveals their regulating role on the direct and indirect output pathways from the striatum
Patrick Aldrin-Kirk, Andreas Heuer, Daniella Ottosson, Marcus Davidsson, Bengt Mattsson, et al.
(2018) Neurobiology of Disease, 109 p.148-162
Journal articleRepairing the brain : Gene therapy
Tomas Björklund
(2018) Journal of Parkinson's Disease, 8 p.123-130
Journal article reviewA novel process of viral vector barcoding and library preparation enables high-diversity library generation and recombination-free paired-end sequencing
Marcus Davidsson, Paula Diaz-Fernandez, Oliver D. Schwich, Marcos Torroba, Gang Wang, et al.
(2016) Scientific Reports, 6
Journal articleIdentification of multiple QTLs linked to neuropathology in the engrailed-1 heterozygous mouse model of Parkinson's disease
Zuzanna Kurowska, Michael Jewett, Per Ludvik Brattås, Itzia Jimenez, Xuyian Kenéz, et al.
(2016) Scientific Reports, 6
Journal articleDREADD Modulation of Transplanted DA Neurons Reveals a Novel Parkinsonian Dyskinesia Mechanism Mediated by the Serotonin 5-HT6 Receptor
Patrick Aldrin-Kirk, Andreas Heuer, Gang Wang, Bengt Mattsson, Martin Lundblad, et al.
(2016) Neuron, 90 p.955-968
Journal articleExpression of Multiple Functional RNAs or Proteins from One Viral Vector.
Tomas Björklund
(2016) Methods in Molecular Biology, 1382 p.41-56
Journal articleCellular Barcoding Links B-1a B Cell Potential to a Fetal Hematopoietic Stem Cell State at the Single-Cell Level
Trine A. Kristiansen, Elin Jaensson Gyllenbäck, Alya Zriwil, Tomas Björklund, Jeremy A. Daniel, et al.
(2016) Immunity, 45 p.346-357
Journal articleNovel AAV-Based Rat Model of Forebrain Synucleinopathy Shows Extensive Pathologies and Progressive Loss of Cholinergic Interneurons.
Patrick Aldrin-Kirk, Marcus Davidsson, Staffan Holmqvist, Jia-Yi Li, Tomas Björklund
(2014) PLoS ONE, 9
Journal articleDirect evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats.
Staffan Holmqvist, Oldriska Chutna, Luc Bousset, Patrick Aldrin-Kirk, Wen Li, et al.
(2014) Acta Neuropathologica, 128 p.805-820
Journal articleContinuous DOPA synthesis from a single AAV: dosing and efficacy in models of Parkinson's disease.
Erik Cederfjäll, Nathalie Nilsson, Gurdal Sahin, Yaping Chu, Elisabeth Nikitidou, et al.
(2013) Scientific Reports, 3
Journal articleA novel α-synuclein-GFP mouse model displays progressive motor impairment, olfactory dysfunction and accumulation of α-synuclein-GFP.
Christian Hansen, Tomas Björklund, Géraldine Petit, Martin Lundblad, Reena Murmu, et al.
(2013) Neurobiology of Disease, 56C p.145-155
Journal articleDysregulated dopamine storage increases the vulnerability to alpha-synuclein in nigral neurons
Ayse Ulusoy, Tomas Björklund, Kerstin Buck, Deniz Kirik
(2012) Neurobiology of Disease, 47 p.367-377
Journal articleDesign of a Single AAV Vector for Coexpression of TH and GCH1 to Establish Continuous DOPA Synthesis in a Rat Model of Parkinson's Disease.
Erik Cederfjäll, Gurdal Sahin, Deniz Kirik, Tomas Björklund
(2012) Molecular Therapy, 20 p.1315-1326
Journal articleMutant huntingtin causes metabolic imbalance by disruption of hypothalamic neurocircuits.
Sofia Hult Lundh, Rana Soylu, Tomas Björklund, Bengt F Belgardt, Jan Mauer, et al.
(2011) Cell Metabolism, 13 p.428-439
Journal articleGene therapy for Parkinson's disease shows promise.
Anders Björklund, Tomas Björklund
(2011) Science Translational Medicine, 3 p.1-79
Journal articleGene therapy for Parkinson's disease.
Tomas Björklund, Jeffrey H Kordower
(2010) Movement Disorders, 25 Suppl 1 p.161-173
Journal articleOptimized adeno-associated viral vector-mediated striatal DOPA delivery restores sensorimotor function and prevents dyskinesias in a model of advanced Parkinson's disease.
Tomas Björklund, Thomas Carlsson, Erik Cederfjäll, Manolo Carta, Deniz Kirik
(2010) Brain, 133 p.496-511
Journal articleA General Chemical Method to Regulate Protein Stability in the Mammalian Central Nervous System
Mari Iwamoto, Tomas Björklund, Cecilia Lundberg, Deniz Kirik, Thomas J. Wandless
(2010) Chemistry and Biology, 17 p.981-988
Journal articleDifferential Transduction Following Basal Ganglia Administration of Distinct Pseudotyped AAV Capsid Serotypes in Nonhuman Primates
Hemraj B. Dodiya, Tomas Björklund, James, III Stansell, Ronald J. Mandel, Deniz Kirik, et al.
(2010) Molecular Therapy, 18 p.579-587
Journal articleGene therapy for dopamine replacement.
Tomas Björklund, Erik Cederfjäll, Deniz Kirik
(2010) Progress in Brain Research, 184 p.221-235
Journal article reviewOptimization of continuous in vivo DOPA production and studies on ectopic DA synthesis using rAAV5 vectors in Parkinsonian rats
Tomas Björklund, Helene Hall, Nathalie Breysse, Charlotte Soneson, Thomas Carlsson, et al.
(2009) Journal of Neurochemistry, 111 p.355-367
Journal articlePositron Emission Tomography Imaging Demonstrates Correlation between Behavioral Recovery and Correction of Dopamine Neurotransmission after Gene Therapy
Ludovic Leriche, Tomas Björklund, Nathalie Breysse, Laurent Besret, Marie-Claude Gregoire, et al.
(2009) Journal of Neuroscience, 29 p.1544-1553
Journal articleGene therapy by enzyme replacement for Parkinson’s disease Optimization of continuous DOPA delivery and development of a candidate vector for clinical application
Tomas Björklund
(2009) Lund University Faculty of Medicine Doctoral Dissertation Series, 2009:117
DissertationGene therapy for dopamine replacement in Parkinson's disease.
Anders Björklund, Tomas Björklund, Deniz Kirik
(2009) Science Translational Medicine, 1 p.2-2
Journal articleScientific rationale for the development of gene therapy strategies for Parkinson's disease.
Tomas Björklund, Deniz Kirik
(2009) Biochimica et Biophysica Acta - Molecular Basis of Disease, 1792 p.703-713
Journal articleDose Optimization for Long-term rAAV-mediated RNA Interference in the Nigrostriatal Projection Neurons.
Ayse Ulusoy, Gurdal Sahin, Tomas Björklund, Patrick Aebischer, Deniz Kirik
(2009) Molecular Therapy, 17 p.1574-1584
Journal articleIn vivo gene delivery for development of mammalian models for Parkinson's disease
Ayse Ulusoy, Tomas Björklund, Stephan Hermening, Deniz Kirik
(2008) Experimental Neurology, 209 p.89-100
Journal article reviewApplications of lentiviral vectors for biology and gene therapy of neurological disorders.
Cecilia Lundberg, Tomas Björklund, Thomas Carlsson, Johan Jakobsson, Philippe Hantraye, et al.
(2008) Current Gene Therapy, 8 p.461-473
Journal articleFuture Cell- and Gene-Based Therapies for Parkinson's Disease
Tomas Björklund, Asuka Morizane, Deniz Kirik, Patrik Brundin
(2008) Therapeutics of Parkinson's Disease and Other Movement Disorders , p.145-156
Book chapterRestoration of the striatal dopamine synthesis for Parkinson's disease: viral vector-mediated enzyme replacement strategy.
Thomas Carlsson, Tomas Björklund, Deniz Kirik
(2007) Current Gene Therapy, 7 p.109-120
Journal article reviewLong-term consequences of human alpha-synuclein overexpression in the primate ventral midbrain.
Andisheh Eslamboli, Marina Romero-Ramos, Corinna Burger, Tomas Björklund, Nicholas Muzyczka, et al.
(2007) Brain, 130 p.799-815
Journal articleMorphometric and psychometric comparisons between non-substance-abusing patients with posttraumatic stress disorder and normal controls
Reza Emdad, David Bonekamp, Hans Peter Sondergaard, Tomas Björklund, Ingrid Agartz, et al.
(2006) Psychotherapy and Psychosomatics, 75 p.122-132
Journal article (letter)Imaging in cell-based therapy for neurodegenerative diseases.
Deniz Kirik, Nathalie Breysse, Tomas Björklund, Laurent Besret, Philippe Hantraye
(2005) European Journal of Nuclear Medicine and Molecular Imaging, 32 p.417-434
Journal article review