Per Svenningsson

Per Svenningsson

Professor/Senior Physician
Visiting address: BioClinicum J5:20, Akademiska stråket 1, Karolinska universitetssjukhu, 17164 Solna
Postal address: K8 Klinisk neurovetenskap, K8 Neuro Svenningsson, 171 77 Stockholm
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About me

  • Per Svenningsson, MD, PhD, is a Professor of Neurology and a PI at the Department of Clinical Neuroscience, Karolinska Institutet. He is also a Senior Physician at the Karolinska University Hospital.

Articles

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Grants

  • Swedish Research Council
    1 January 2025 - 31 December 2028
    This programme aims at providing better biomarkers anbd mechanism-based therapies for two common diseases: Parkinson´s disease (PD) and Major depressive disorder (MDD). Besides motor symptoms, many PD patients suffer from depression and dementia. There are several symptomatic therapies towards motor symptoms of PD, but there is no therapy that slows down disease progression. GLP-1 agonists show promise as disease modifying therapies, but their mechanism of action are poorly understood. PD is characterized by accumulation of α-synuclein enriched Lewy bodies. Misfolded GPR37 is a core component of Lewy bodies and induces dopamine neurodegeneration. Our unpublished data suggests that it is the cleaved N-terminus of GPR37 which accumulates in dopamine neurons. MDD is a leading cause of Disability Adjusted Life Years. The glutamate-based compound, s-ketamine, was recently approved as a fast acting antidepressant. Psilocybin, a more classical psychedelic, which acts via serotonin G protein-coupled receptors (GPCRs) has also fast acting antidepressant properties. Recent breakthroughs in revealing atomic resolution structures for GPCRs in complex with ligands and intracellular effectors enables functional understanding and in silico screening of molecules to GPCRs. This translational programme will continue to reveal mechanisms whereby GPCRs, particularly GPR37, TAAR1 and GLP-1R, and a GPCR adaptor protein, p11, serves as biomarkers and therapy targets in PD and/or MDD.
  • Swedish Research Council
    1 January 2024 - 31 December 2026
    Parkinson’s disease and related disorders are the second most common neurodegenerative diseases. Parkinsonian disorders present with similar symptoms at their onset. The diagnosis, which is based on clinical criteria and follow-up, is challenging. An uncertain or wrong diagnosis may lead to inappropriate treatment and unwanted side effects for the individual patient and  increased costs for the healthcare system. Early, precise diagnosis is crucial for the development of treatments targeting molecular mechanisms of underlying disease.The aim of the present work is to identify characteristic patterns of cerebral blood flow (CBF) and their association with dopamine transporter (DAT) availability in parkinsonian disorders. This will be used to develop methods for precise differential diagnosis with PE2I positron emission tomography (PET) and supervised machine learning (ML). 18F-FE-PE2I PET/CT scans providing both CBF and DAT availability from a single scan will be acquired in a cohort of at least 2500 patients from five Swedish university hospitals and will, together with comprehensive clinical diagnosis, be used to train ML-based classification.The project will result in a more precise method for differential diagnosis of parkinsonian disorders that will be available beyond specialized academic centres. It will further increase understanding of parkinsonism, support appropriate treatment in individual patients, and provide improved imaging biomarkers for drug development.
  • Swedish Research Council
    1 January 2023 - 31 December 2026
    The aim of this project is to elucidate L-DOPA-induced dyskinesia (LID) in Parkinson’s disease (PD) by clarifying the pathophysiological mechanisms involved, which are currently unknown although LID is one of the most difficult problems facing patients with PD. We will use innovative matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to simultaneously image and quantify neurotransmitter and neuropeptide systems, endogenous metabolites and lipids, and proteins directly in brain tissue sections. Achievement of this aim will be facilitated by access to a biobank of brain tissues of non-human primates providing unprecedentedly comprehensive coverage of an LID model and controls, neurotoxic and genetic rodent PD models, as well as human brains and cerebrospinal fluid. We will develop methodology for highly multiplex protein imaging by MALDI-MSI. To enable imaging of single cells directly in tissue sections we will increase the spatial resolution to &lt
    1 µm by using deep learning technology. We will also design and synthesise chemical tools enabling imaging of hitherto undetectable endogenous substances in the samples, and apply pathway analysis to determine the signalling status of the cells, quantitatively, from measured expression levels of molecular species. Thus, the project will provide novel insights into the underlying mechanisms of LID (and PD), which may enable development of new therapy targets and/or clinically useful biomarkers.
  • Swedish Research Council
    1 January 2023 - 31 December 2026
    Parkinson’s disease (PD) is the fastest growing neurodegenerative disease, and the development of a disease-modifying therapy is the most important unmet goal in the therapy of PD. Preclinical and clinical studies have shown promising results of the anti-inflammatory agent  Montelukast in PD. We have now designed a multi-center, randomized, double-blind, placebo-controlled trial with Montelukast in PD.PICO Population: Diagnosis of PD. Males or Females. H&Y stage ≤ 2. ≥35 and ≤80 years of age. Signed informed consent to participate in the trial. Clinical diagnosis &lt
    4 years. Ability to self-administer the trial drug.  Intervention: 18 months of daily buccal Montelukast 2x30 mg. Control: Placebo. Primary outcome: Change of MDS-UPDRS motor score in OFF medication state at 18 months. Secondary outcomes are changes in effects on non-motor symptoms of Montelukast using MDS-NMSS and HADS. There is also a safety objective and several exploratory outcomes.Ninty patients with early-moderate PD in Stockholm, Lund, Uppsala, Göteborg and London will be recruited. Ethical permits and MPA applications will be submitted in the beginning of 2023. Patient recruitment will start in April 2023 and the last patient follow-up will be in March 2026 followed by data analysis/reporting. The study is endorsed by the Swedish PD patientorganization and Cure Parkinson. If this RCT is successful and since Montelukast is repurposed, patients will soon benefit from the therapy.
  • Swedish Research Council
    1 January 2023 - 31 December 2026
    Background: The age standardised rate of yearly new cancer cases is 190/100 000 globally, by WHO. 30-40% of these will develop depression. There is currently no specific antidepressant treatment regime implemented in the cancer population. This is in spite of the specific needs given by concurrent cancer treatments, limited quality of life from the cancer per se and the often limited life expectancy from a cancer disease. A single dose of psilocybin combined with 3 hours of psychological support has shown rapid (within days) and long term (months or years) antidepressant effect in several small studies in different cancer populations. Large, well designed RCTs are still lacking, as is response predictors for treatment guidance. I am PI of the first RCT of psilocybin treament of depression in Sweden, expected to end randomisation in june 2022. CAPSI: 100 patients with cancer and depression will be randomised to psilocybin or active placebo (2:1) at 4 different regions in Sweden during 2024-2025. Primary end point is depressive symptoms 6 weeks post dose and follw up is 6 months. All subjects will undergo EEG and blood sampling, a subsample (n=50) will also undergo MEG and fMRI, and 25 of them also PET, in order to develop a EEG proxy response signature. Together with markers in blood we will develop a predictor model for psilocybin treatment response. All data will be used to motivate a phase three study with the same PICO and further development of the response markers.
  • Swedish Research Council
    1 January 2023 - 31 December 2025
  • Swedish Research Council
    1 January 2023 - 31 December 2026
    Life means combining motor-cognitive skills, e.g., walking, talking and navigating. Aging or neurological diseases, e.g., Parkinson’s disease (PD) compromises these skills needed for an independent life. It is uncertain which brain alterations lead to these difficulties and how to target these heterogenous motor-cognitive difficulties. Current treatments apply a "one-size-fits-all" approach, which needs to evolve towards personalized rehabilitation, reaching beyond a simple adaption to disease severity.Our multimodal project combines physiotherapy, neurology, psychology and neuroimaging to characterize motor-cognitive skills during complex walking, identify underlying brain alterations and subtype PD to inform a novel exercise approach for people with PD. This 5 years proposal has 4 stages: 1) Exploring brain alterations and links to the motor-cognitive skills in healthy and PD 2) PD subtyping using neuroimaging, motor, cognitive and clinical data 3) Characterization of exercise responsiveness in PD and 4) Development and testing of a personalized motor-cognitive exercise program. We combine novel techniques for data collection with in-depth analysis of existing data (EXPANd trial). The results will have an immediate application and clinical relevance for personalized rehabilitation in older and PD. There is no cure for PD yet, thus positive findings would revolutionize treatment, giving new hope to patients for a life with improved health, independence and higher quality.
  • Swedish Research Council
    1 January 2022 - 31 December 2027
    We propose an innovative interdisciplinary research environment to investigate the pathophysiology of dementia in Parkinson’s disease (PDD) and Lewy Body dementia (LBD). Based on the identified molecular fingerprints we will also develop diagnostic and prognostic wet biomarkers. PDD and LBD are difficult to diagnose in the clinic and no diagnostic test is available. Differentiation from parkinsonian plus syndromes and Alzheimer’s disease is a major challenge and will be examined. The research environment consists of a unique combination of spatial omics methodologies, i.e., spatial transcriptomics, -proteomics, and -mass spectrometry combined with state-of-the-art bioinformatic tools. We synthesise chemical tools to enable detection low-abundant potential biomarkers compatible with the spatial analysis of a particular imaging modality. Clinical samples are available from the Stockholm BioPark cohort and King’s College Dementia Brain biobank. First, we will examine a comprehensive set of cortical post-mortem brains from control, PD, PDD and LBD. The biomarker potential of pathologically relevant molecules will then be assessed in CSF and plasma from a cohort of 650 patients. We aim at stimulating the needed of collaborations in correlated spatial omics, promoting and disseminating its benefits, and paving the way for its technological advancement and implementation in the neurological field to ultimately impact on clinically unmet medical needs for PDD and LBD patients.
  • Swedish Research Council
    1 January 2021 - 31 December 2023
  • Swedish Research Council
    1 January 2020 - 31 December 2024
  • Knut and Alice Wallenberg Foundation
    1 January 2019 - 1 January 2024
  • Swedish Research Council
    1 January 2019 - 31 December 2022
  • Swedish Research Council
    1 January 2019 - 31 December 2022
  • Swedish Research Council for Health Working Life and Welfare
    1 December 2018 - 30 November 2026
    As the prevalence of chronic illness increases, the demands on healthcare services change. The few hours per year that persons with chronic conditions see healthcare professionals represent a mere fraction of their 24/7 lived experience of coping with their condition. Without patient participation no treatment can be carried out
    thus healthcare services are co-produced. This reality requires a shift from professional-oriented care toward patient-oriented supported self-care. Co-care refers to the decisions and activities shared by patients, their informal caregivers, and professionals, aimed at achieving goals valued by the patient. Consequently, in contrast to involve patients in healthcare, healthcare needs to get involved in people’s self-care, to the extent that the patient needs and desires. Making this shift, however, has been challenging for health care practice.Given this implementation gap, the current program is based on five patient-driven co-care innovations and aims to study how new models of self-care and co-care are best implemented in everyday health care practice and patients’ lives, supported by eHealth. This program is collaboration with patients, their informal caregivers and healthcare providers, to ensure that the research meets patients’ needs. The program is conducted in two phases studying: 1) the implementation of the five patient-driven co-care innovations and the development of patient-valued outcome measures and 2) the impact of the co-care innovations on clinical practice, care organization and patient-valued outcomes, the spread and scaling up of the innovations and production of best practice guidelines. Multiple research designs (e.g. comparative case studies, participatory workshops, adaptive intervention design) will be used. The program generates knowledge that enables people with chronic conditions, their informal caregivers and formal healthcare providers to effectively engage in co-care.
  • Swedish Research Council
    1 December 2017 - 31 December 2022
  • VINNOVA
    3 July 2017 - 29 June 2018
  • Swedish Research Council
    1 January 2017 - 31 December 2020
  • Swedish Research Council
    1 January 2016 - 31 December 2019
  • Swedish Research Council
    1 January 2016 - 31 December 2019
  • European Research Council
    1 August 2015 - 31 January 2022
  • Show more

Employments

  • Professor/Senior Physician, Neurology, Department of Clinical Neuroscience, Karolinska Institutet, 2021-
  • Senior Physician, 2016-
  • Professor/Specialist Physician, Department of Clinical Neuroscience, Karolinska Institutet, 2012-2021

Degrees and Education

  • Doctor Of Philosophy, Department of Physiology and Pharmacology, Karolinska Institutet, 1998
  • University Medical Degree, Karolinska Institutet, 1996

Supervision

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