The Neuro-SysMed Seminars

Topic:  ALS

Speaker: Ole-Bjørn Tysnes

Title: «About ALS management and new emerging treatments” 

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday January 22, 2025, at 11:30–13:00 (lunch 11:30–12:00).

Langage: English

Abstract: ALS is characterised by progressive paresis is in arms or legs, or it may start as slurred speech. Five to 10% of cases are familial ALS. The disease occurs with an incidence of 3 per 100,000 per year. The disease is usually rapidly progressive with a median survival of approximately 2-3 years. Ten per cent of the cases may live as long as 10 years.

ALS management has the goal to make the patient live at home during the entire disease. Consideration has to be taken towards the possibilities in their apartment/house. Other important issues are communication difficulties, oral secretion, nutrition, management of palsies and social security. Availability of aids and respiration problems are important issues to follow up. Symptoms develop gradually and ALS is managed by a team with various specialists. Successful ALS management will end up with palliative care at home. Taking care of spouse and family is very important in such cases.

Riluzole is the only accepted and registered medical treatment for ALS today. The effect is rather scarce. During the last few years possibilities of treatment of genetic subgroups of ALS have come up. Recently Tofersen is registered as treatment for SOD ALS in the EU. In Norway it is not yet registered. There is an ongoing trial on FUS ALS which is promising. Possibilities of treating genetic subgroups of ALS has induced a discussion whether all cases of ALS should be genetically tested. Genetic ALS is however quite rare in sporadic ALS, with exception of the C9orf expansion. Currently there is no available treatment for this subgroup over genetic ALS.

Topic:  TECH-CARE

Speaker: The Care node by Bettina Husebø, Zoya Sabir, Haakon Reithe, Valentina Casadei, and Kamilla Haugland-Pruitt 

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday February 12, 2025, at 11:30–13:00 (lunch 11:30–12:00).

Langage: English

Abstract: The Care node led by Bettina S. Husebø, will bring talks from Zoya Sabir, Haakon Reithe, Valentina Casadei, and Kamilla Haugland-Pruitt on the topic of TECH-CARE. 

They will look at wearable sensor technologies and how the rich digital data they provide could enhance understanding of symptoms, behaviors, and response to treatment in older adults with complex conditions, such as people with dementia and Parkinson’s disease.

In this seminar, Zoya Sabir (CC.AGE project) will address challenges related to the assessment of dietary intake and hydration status using traditional methods and explore the potential use of sensor technology for assessment of hydration status. Haakon Reithe (ActiveAgeing: DIGI.PARK study) will showcase a novel way of quantifying tremors in people with Parkinson’s disease in free living conditions. This method is data-independent and provides an index in known tremor frequencies. To validate, we compare most-affected with least tremor-affected hand.  Valentina Casadei (DARK.DEM study) will present advancements in technology for heart rate and respiration monitoring through cutting-edge wearable devices. Kamilla Haugland-Pruitt (5-D project) asks the question: how can we objectively know when a person with dementia is reaching the end-of-life? Smart watches and radar installation will give us novel information which can potentially, with help of algorithms, predict death.

Title:  The Complexity of Medical Phenomena

Speaker: Professor Roger Strand, Centre for the Study of the Sciences and the Humanities, University of Bergen

Chair: Jan Reinert Karlsen from Neuro-SysMed's Responsible Research and Innovation & Patient and Public Involvement (RRI/PPI) Node

Place: NB: Other place than usual! The auditorium Olavssalen in Gamle Hovedbygning (campus Haukeland University Hospital, Bergen)

Time: Wednesday March 5, 2025, at 11:30–13:00 (lunch 11:30–12:00).

Langage: English

Abstract: While the words "complexity" and "complex" abound in medical research, modern medicine has by and large developed by means of reductionist approaches that implicitly assume that medical phenomena are simple. This has led to some great successes and innumerable minor, partial successes, sometimes at the cost of over-treatment and inappropriate medicalization of biological and social phenomena. 

In his talk, Roger Strand will clarify the terms "simple", "complicated" and "complex". Examples will be given to illustrate how medical research proceeds by disregarding complexity and arriving at results that, ironically, may give rise to treatments that produce their own complexity in clinical practice and lived experience. In fact, modern medicine only rarely develops "silver bullets" that simplify the lives of patients and clinicians. Instead, the complexity and costs of the health system increases.

Roger Strand holds an MSc and PhD in biochemistry and is a Professor at the Centre for the Study of the Sciences and Humanities, UiB. He has studied complexity in science, nature and public policy for more than three decades. His research on the complexity of medicine has mainly focused on cancer, and he has been affiliated with the CCBIO since its inception in 2013. At the Faculty of Medicine, UiB, he has worked with several of the Faculty's greatest minds, including Torgeir Flatmark, Lars A. Akslen and Caroline Engen. 

Title:  Hunting down misfolded proteins: seed amplification assays in neurodegenerative diseases

Speakers: Fabio Moda and Arianna Ciullini

Chair: Charalampos Tzoulis

Place: NB: Other place than usual! The auditorium Olavssalen in Gamle Hovedbygg (campus Haukeland University Hospital, Bergen)

Time: Monday March 17, 2025, at 09:00–10:10

Langage: English

Abstract: Neurodegenerative diseases, including prion diseases, Alzheimer’s disease and other dementias, Parkinson’s disease, and motor neuron diseases, are characterized by the pathological accumulation of misfolded proteins in the brain, which serve as disease-specific biomarkers (DSBs). However, their clinical diagnosis remains challenging, particularly in the early stages, due to the lack of reliable peripheral biomarkers. Identifying disease-specific and peripheral biomarkers is crucial for enabling early detection, improving prognosis, and monitoring disease progression. A major breakthrough in this field is the development of Seed Amplification Assays (SAAs), highly sensitive techniques such as Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking-Induced Conversion (RT-QuIC). These methods allow for the detection of misfolded proteins in peripheral tissues, providing a powerful tool for early and differential diagnosis. This seminar will explore the key applications of SAAs in neurodegenerative disease research and highlight their transformative potential in clinical diagnostics. Fabio Moda will introduce the fundamental principles of SAAs and their applications in diagnosing neurodegenerative diseases. Arianna Ciullini will present some of the latest findings from the Specialized Biochemistry Laboratory of Neurological Proteinopathies, directed by Fabio Moda at Carlo Besta Institute in Milan.

Fabio Moda is an assistant professor of clinical biochemistry and clinical molecular biology at the University of Milan, Department of Medical Biotechnology and Translational Medicine. He performs clinical and research activities at the Laboratory of Clinical Pathology at Fondazione IRCCS Istituto Neurologico Carlo Besta. He is responsible for the BSL3 facility dedicated to the diagnosis of human and animal prion diseases. He also leads the Laboratory of Specialized Biochemistry of Neurological Proteinopathies which is aimed at developing innovative tests, mainly involving the seed amplification assays, for the identification of peripheral biomarkers in biological samples of patients with different neurodegenerative disorders, including Parkinson’s disease, multiple system atrophy, dementia with Lewy bodies, amyotrophic lateral sclerosis, Alzheimer’s and prion diseases. Since 2020, he is a scientific committee member of the Italian Association of Neurology focused on Dementia (SINdem) and has received several national and international grants supporting his research activities.

Arianna Ciullini is a health researcher at the Laboratory of Clinical Pathology at Fondazione IRCCS Istituto Neurologico Carlo Besta under the supervision of Dr. Fabio Moda. Trained as a molecular biotechnologist, her research focuses on the discovery of new peripheral disease-specific biomarkers for α-synucleinopathies. She is involved in several projects aimed at detecting misfolded α-synuclein in olfactory mucosa, skin, urine and blood samples from patients with alpha-synucleinopathies at different disease stages (overt disease, prodromal stages – iRBD) using the Seed Amplification Assay (SAA).

Title:  Somatic mutations in synucleinopathies

Speaker: Christos Proukakis, Professor of Neurology and Neurogenetics at the University College London Institute of Neurology, and Honorary Consultant Neurologist at the Royal Free London. 

Chair: Charalampos Tzoulis

Place: NB: Other place than usual! The auditorium Olavssalen in Gamle Hovedbygg (campus Haukeland University Hospital, Bergen)

Time: Wednesday, May 7, 2025, at 12:00–13:30 (light lunch from 12.00-12.30, followed by the seminar 12.30-13.30)

Language: English

Abstract: Parkinson’s disease (PD) and multiple system atrophy (MSA) are synucleinopathies, that is, neurodegenerative disorders characterised by aggregation of the alpha-synuclein protein. Although PD (usually) and MSA (always) are sporadic, an alternative genetic contribution could arise through somatic mutations, which lead to mosaicism. The Proukakis lab uses a number of techniques to investigate this in post-mortem brain tissue, from fluorescent in situ hybridisation to DNA sequencing, using tissue DNA or amplified single cell genomes, sequenced with short and long reads, whole genome or targeted. They have data suggesting that somatic copy number gains of the alpha-synuclein gene may drive MSA, and they are currently finalising a genome-wide large somatic CNV analysis of 4,000 single cells from PD and control brains.

Christos Proukakis is a Professor of Neurology and Neurogenetics at the University College London Institute of Neurology, and practices clinically as Honorary Consultant Neurologist at the Royal Free London. He completed his medical degree in Cambridge and Oxford and his specialty training and PhD in London. His clinical and research focus is Parkinson’s disease/synucleinopathies. He hypothesized and is investigating the role of somatic mutations in the brain.

Topic:  Drug screening

Speaker: Aurora Martinez and Gloria Gamiz from Neuro-SysMed's Drug Discovery Node

Title: Screening and development of drugs for neurological targets

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday May 21, 2025, at 11:30–13:00 (lunch 11:30–12:00).

Langage: English

Abstract: The discovery of drugs for neurological targets typically begins with precise target identification and validation, followed by robust screening strategies. High-throughput screening (HTS) of large compound libraries, including approved drugs, is performed with subsequent validation in cellular assays using disease-relevant cells. For unknown or complex targets, phenotypic screening  assays can also be employed. Structural understanding of the target aids in preclinical hit-to-lead optimization, leading to the nomination of effective and safe candidates for clinical trials. As an example, we will present a screening campaign that identified a non-steroidal anti-inflammatory drug as a stabilizer of tyrosine hydroxylase (TH), the enzyme crucial for dopamine synthesis. The identified drug showed high binding affinity and significant stabilizing effects on TH and a genetic variant causing TH deficiency (THD), a rare disorder associated with reduced dopamine and symptoms ranging from dystonia to parkinsonism. Efficient therapeutic alternatives to levodopa are urgently needed for THD. In silico docking, molecular dynamics simulations, analogue testing, and site-directed mutagenesis revealed the drug's binding site, offering potential for further optimization. Critical considerations such as blood-brain barrier permeability and neurotoxicity also guide the preclinical development of drugs for neurological targets.

Title:  NAD Augmentation as a Disease Modifying Strategy for Neurological Diseases

Speaker: Charalampos Tzoulis/Christian Dölle

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday, June 4, 2025, at 11:30–13:00 (lunch 11:30–12:00).

Langage: English

Abstract: Neurodegenerative diseases pose a significant and rapidly growing global health challenge. Yet, there are still no effective therapies capable of delaying or halting their progression. In recent years, augmentation of nicotinamide adenine dinucleotide (NAD) has emerged as a promising disease-modifying strategy that targets multiple key disease pathways across multiple neurodegenerative diseases, such as mitochondrial dysfunction, energy deficits, proteostasis, and neuroinflammation. Several early clinical trials of NAD augmentation have been completed, and many more are currently underway, reflecting the growing optimism and urgency within the field. We will discuss the rationale and evolving therapeutic landscape of NAD augmentation. We will argue that to fully realize its therapeutic potential, it is essential to determine the specific contexts in which NAD supplementation is most effective and to address crucial knowledge gaps.

More reading: See the recent publication NAD augmentation as a disease-modifying strategy for neurodegeneration by Christian Dölle and Charalampos Tzoulis.

Title:  Different Disease Pathways to Idiopathic Parkinson’s Disease:  Three Genetically-Defined Subgroups with Different Treatment Responses in Phase III Disease-Modifying Trials and Distinct Clinical Trajectories

Speaker: Antony Cooper, Research Director - Australian Parkinson's Mission, Garvan Institute of Medical Research, and UNSW Sydney, School of Clinical Medicine, Australia

Chair: Charalampos Tzoulis

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday, June 25, 2025, at 11:30–13:00 (light lunch from 11:30-12.:0, followed by the seminar 12.00-13.00)

Registration: Please use this registration link

Who: Open to all interested

Language: English

Abstract: Dr. Cooper is a cell & molecular biologist and geneticist with strong research interests in the causative mechanisms of Parkinson’s disease and therapeutic approaches to successfully treat PD patients, especially with respect to slowing disease progression in idiopathic patients. Recently, in his role as the Research Director of the Australian Parkinson’s Mission, Dr. Cooper and his collaborators have made substantial progress in identifying three genetically-defined subgroups of idiopathic patients whose analysis supports three differing disease mechanisms. In his talk, he will show results from this intriguing recent work.

Topic: ALS – update on genetics, biomarkers and clinical studies at Neuro-SysMed.

Speakers: Ole-Bjørn Tysnes and Tale Bjerknes

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday January 10, 2024, at 11:30–13:00 (lunch 11:30–12:00).

Abstract: Tale Bjerknes and Ole-Bjørn Tysnes will talk about current ALS-studies at Neuro-SysMed. The ALS node at Neuro-SysMed has one clinical trial on therapeutic intervention, the NO-ALS trial, which has currently included more than 250 patients. This study is focusing on the effect of a combination of nicotineamide riboside and pterostilbene in ALS. They are also organising a clinical study on the quality of life upon decisions of life-prolonging respiratory treatment in ALS. The effect of such discussions on quality of life of patients and their families has not been well studied in ALS. Both studies are national studies including patients from all over Norway.

Tale and Ole-Bjørn will also talk about the rationale behind the ALS node's treatment study, give us the news on genetics of ALS in Norway, and present upcoming ALS biomarkers. These biomarkers may be useful in diagnosing ALS, but will probably be even as important when studying the effect of study drugs in ALS trials. Convincing data show that the level of neurofilament light chain in the blood represent a prognostic marker and a marker for therapy effect in ALS.

Speakers: From the Care node: Bettina Husebø, Elise Førsund, Monica Patrascu and Brice Marty.

Title: Can digital phenotyping replace the care for my granny?

Chair: Bettina Husebø

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday February 14, 2024, at 11:30–13:00 (lunch 11:30–12:00). Please register before Feb. 8 at 11 AM if you wish to join the lunch.

Abstract: Norway is placed at the European top in resource use for health and care services (Health Commission Report, 2023) but already now, municipalities are struggling with a growing staffing crisis. Focus on technical aids is well established in diagnosis, treatment, and rehabilitation. Welfare technology in the care services is also becoming increasingly widespread and contributes to better quality and a greater scope of services as a supplement to necessary care for patients and relatives. However, the technology is often not tested and implemented in those with complex conditions and people with neurological diseases, living at home and in nursing homes. Ethical approval processes are demanding when technology and artificial intelligence are to be used by those who are no longer able to give informed consent. In this seminar we are briefly addressing digital phenotyping in dying nursing home patients with dementia (B. Husebø, ERC project); smart living environments at Helgetun (Elise Førsund, ActiveAgeing); the development of a mobile platform to support safely and independently living at home with complex conditions (Monica Patrascu, CC.AGE), and how to analyze digital data by knowledge-based machine learning (Brice Marty, Algorithms class). 

Title: Restructuring Neurology: Responsible Research and Innovation (RRI)

Chair: Caroline Engen, postdoctoral fellow in the Neuro-SysMed research group Philosophy of Neurodegeneration, led by Jan Reinert Karlsen at SVT.

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday March 13, 2024, at 11:30–13:00 (lunch 11:30–12:00).

Abstract: While the work at Neuro-SysMed is mainly dedicated to improving the lives of people living with and dying from severe neurological conditions, Neuro-SysMed's ambition extends to redefining Norwegian Clinical Neurology through a systems medicine approach. By integrating cutting-edge technologies and medical practice, the overall objective is to leverage data from clinical trials for the identification of precise markers aiding early disease detection, delineation of more accurate disease categories, enhanced predictive abilities, and refined interventions. As such, Neuro-SysMed is about advancing neurological practices in specific ways and through specific approaches, reflecting and co-producing broader developments and discourses related to how medicine could and should be practiced in the future. This ambition, of restructuring neurology, raise a range of questions related not only to severe neurological conditions but also in relation to philosophical and ethical dimensions of healthcare and society at large.  Incorporating Responsible Research and Innovation (RRI) and patient and public involvement (PPI) as key components, Neuro-SysMed emphasizes a commitment to weaving these critical considerations into its core activities.

In the upcoming talk titled "Restructuring Neurology: Responsible Research and Innovation (RRI)", Caroline Engen, a postdoctoral researcher at Neuro-SysMed, will elucidate the concept of Responsible Research and Innovation (RRI). She will trace RRI's roots back to some of its philosophical underpinnings and its empirical foundations in the history and sociology of science. Additionally, Engen will discuss RRI's evolution into a governance tool within European and Norwegian research policy frameworks (e.g. Horizon 2020, The Norwegian Research Council). The talk will particularly highlight the significance of RRI for medical research broadly, with a focused examination of its relevance within the specific context of Neuro-SysMed.

Topic: Dementia

Title: "Disease mechanisms in Alzheimer's disease"

Speaker: Kristoffer Haugarvoll

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday April 24, 2024, at 11:30–13:00 (lunch 11:30–12:00).

Speaker: Svein Isungset Støve, Department of Biomedicine, University of Bergen, Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen, and the K.G. Jebsen Center for Translational Research in Parkinson’s Disease, University of Bergen.

Topic: Screening for activity modulators of targets relevant for Parkinson’s disease and hyperkinetic movement disorders

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday May 15, 2024, at 11:30–13:00 (lunch 11:30–12:00).

Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is characterized by loss of dopamine signaling and degeneration of dopaminergic neurons in the substantia nigra. To this day, there are no available treatment options that can delay or stop disease progression, and there is an urgent need for identification of new drugs that can be clinically tested for a symptomatic or disease modifying effect. 

In this talk I will present work from screening projects on two different targets, the Vesicular Monoamine Transporter 2, and Mitochondrial Complex I. The vesicular monoamine transporter 2 (VMAT2) is a member of the SLC18 family of transporters and responsible for the uptake of monoamine neurotransmitters such as dopamine, serotonin, histamine, epinephrine, and norepinephrine into synaptic vesicles for subsequent release upon neurotransmission. Due to the central role of VMAT2 in monoamine signaling, it is an interesting potential drug target of disorders such as Parkinson’s disease (activators) or for the treatment of hyperkinetic movement disorders (inhibitors). We have screened VMAT2 for small molecule modulators of substrate transport and identified several new inhibitors of VMAT2. These inhibitors are previously approved drugs that are promising candidates for a future use in treatment of hyperkinetic movement disorders such as tardive dyskinesia. 

Further, we have initiated a project aimed at identifying molecular chaperones or functional activators of mitochondrial complex I by cellular screening approaches. Such compounds could be used to reduce mitochondrial complex I dysfunction and have a potential future use in treatment of Parkinson’s disease. In addition to results from the screening projects described above, I will give an overview of different relevant screening approaches, what opportunities there are for initiating new screening projects in Bergen, and where we hope to be in the future. 

Newly appointed Honorary Doctor at UiB Alberto Ascherio lead the international research team who showed a direct link between multiple sclerosis (MS) and the Epstein Barr virus. Could this also lead to a vaccine against MS? Join us in a lecture by Dr. Alberto Ascherio May 23rd at Haukeland University Hospital.

Speaker: Professor Alberto Ascherio, Harvard T.H. Chan School of Public Health and Harvard Medical School 

Topic: EBV causes MS: does it also drive MS pathology?

When: Thursday May 23, 2024 at 12.00-13.00 (lunch from 11.30)

Place: Auditorium 1, BB building, Haukeland University Hospital, Bergen

Host: Neuro-SysMed by Kjell-Morten Myhr. Introduction by Dean Per Bakke.

Who: Open to all interested

Topic: Bioinformatics

Title: Leveraging million single-cell data for clinical trials and precision medicine in neurological diseases

Speaker: Dimitros Kleftogiannis

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday September 11, 2024, at 11:30–13:00 (lunch 11:30–12:00).

Abstract: Recent advancements in single-cell omics technologies have profoundly enhanced our understanding of complex cellular systems, offering broad applications in both basic science and clinical research. Techniques such as single-cell RNA sequencing (scRNA-seq) and high-dimensional cytometry, including Spectral Flow Cytometry, Mass Cytometry by Time-of-Flight (CyTOF), and Imaging Mass Cytometry (IMC), are emerging as crucial tools for refining diagnostic and therapeutic strategies in neurological diseases. However, the analysis of high-dimensional single-cell data presents significant challenges, necessitating the development of innovative analytical approaches. This presentation will begin by providing an overview of key single-cell technologies and the common challenges encountered when analyzing large-scale single-cell datasets. We will then illustrate the application of advanced computational techniques used to analyze over 100 million single cells from patients with Relapsing-Remitting Multiple Sclerosis (RRMS) who participated in the RAM-MS clinical trial. The discussion will focus on the short-term and long-term impacts of Autologous Hematopoietic Stem Cell Transplantation (HSCT) on the immune profiles of RRMS patients, highlighting potential avenues for identifying biomarkers predictive of clinical outcomes.

Short bio: Dimitrios Kleftogiannis is a Senior Bioinformatician and Co-Leader of the Bioinformatics Node at the Neuro-SysMed Centre for Clinical Treatment Research. In his current role, he specializes in the analysis of single-cell data from patients with multiple sclerosis, contributing towards the identification of predictive biomarkers. Dimitrios has extensive experience in the analysis of omics datasets across various technologies and is the developer of several innovative bioinformatics methods and tools. Before joining Neuro-SysMed, he held research positions at the Centre for Cancer Biomarkers (CCBIO) at the University of Bergen, the Agency for Science Technology and Research (A*STAR) in Singapore, and the Institute of Cancer Research (ICR) in London, UK.

Title:  DRONE perspective on how drug consumption is associated with neurodegenerative diseases 

Speaker: Julia Romanowska

Julia is a bioinformatics expert (senior engineer) at BIOS, where she uses her expertise in data science, bioinformatics, biostatistics, programming, and data visualization to explore big data, efficiently run complex analyses, and visualize results. She is involved in various projects, among others, as co-PI of the DRONE project (Drug Repurposing fOr NEurological diseases) at IGS/Neuro-SysMed and an active researcher in the START project (Study of Assisted Reproductive Technology), at the Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo. 

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday October 23, 2024, at 11:30–13:00 (lunch 11:30–12:00).

Abstract: DRONE (Drug Repurposing fOr Neurological disEases) project has as a goal to use agnostic approach and epidemiological methods to screen for associations between drug usage and being diagnosed with a neurodegenerative disease, such as Parkinson’s (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD). 

In this presentation, Julia will give a brief summary of what the group has achieved up till now and what is planned for the nearest future. She will focus on two projects where the group is searching for drugs that can be repurposed to treat PD patients. In these projects, they are collaborating with several other countries to make their results robust and to confirm epidemiological findings with experiments in vitro and in vivo. 

Note that some of the results presented are preliminary and confidential, therefore we ask you not to take pictures or recordings. 

Topic:  Epstein-Barr virus infection; a treatable cause of multiple sclerosis?

Speakers: Kjell-Morten Myhr and Øivind Torkildsen

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday November 27, 2024, at 11:30–13:00 (lunch 11:30–12:00).

Topic:  Parkinson's disease

Speaker: Charalampos Tzoulis

Title: "Tackling the rising challenge of α-synucleinopathies: is there light at the end of the tunnel?” 

α-synucleinopathies are a group of relentlessly progressive, debilitating, and incurable neurodegenera-tive disorders, comprising Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Most common among them is PD, with ~10 million affected people worldwide, expected to double by 2040. Hence, PD is now regarded as one of the fastest growing cause of neuro-logical related disability worldwide. I will give an overview of the challenges hindering therapeutic breakthroughs for α-synucleinopathies, and strategies by us and others to circumvent these obstacles.

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday December 11, 2024, at 11:30–13:00 (lunch 11:30–12:00).

Mini Symposium January 18, 2023

Place: The auditorium in Bikuben, Jonas Lies vei 69 (campus Haukeland University Hospital)

Time: Wednesday January 18 at 10:00 - 16:20

Program 

10.00-11.00: Neuro-SysMed activities by Kjell-Morten Myhr, Director and Charalampos Tzoulis, Co-director, Neuro-SysMed
11.00-12.00: Lunch (free of charge, register within Thursday January 5 at 11.00)
12.00-13.00: Seminar: “Microglia in multiple sclerosis – pathogenesis and imaging” by Prof. Laura Airas, University of Turku. Chair: Kjell-Morten Myhr
13.00-13.15: Break 

Abstract for the Airas lecture: Positron emission tomography (PET) gives an opportunity to quantitate the expression of specific molecular targets in vivo and longitudinally in brain, and thus enhances our possibilities to understand and follow up brain disease-related pathology. TSPO-binding radioligands have been used to detect activated microglial cells at different stages of multiple sclerosis (MS). There is strong consensus that with advanced MS disease, there is increased microglial activation both in the normal appearing white matter and at the edge of chronic active (smoldering) lesions.  The presentation will discuss the PET imaging modalities relevant for MS today, including the main findings that have improved our understanding of the pathogenesis of progressive MS. 

Junior Symposia kick-off:
13.15-13.30: Introduction 
13.30-14.00: “Our experience of great benefits for students attending Junior Symposia at CCBIO”. Keynote lecture by Prof. Lars A. Akslen, Director at CCBIO, UiB
14.00-14.15: Coffee break
14.15-14.40: “Respiratory chain integrity in Parkinson’s disease skeletal muscle” by Simon Ulvenes Kverneng
14.40-15.05: “Towards older age at Multiple Sclerosis onset?” by Andrea Habbestad
15.05-15.20: Coffee break
15.20-15.45: “Wearable sensing technology in research for Parkinson’s disease: experience from the field” by Haakon Reithe
15.45-16.05: “Research stay abroad. My experiences from Amsterdam” by Ingrid Anne Lie
16.05-16.20: Concluding remarks 

Speaker: Christian Dölle, Neuro-SysMed researcher on Parkinson's Disease and NAD-metabolism at the University of Bergen and Haukeland University Hospital 

Chair: Charalampos Tzoulis 

Title: Cell models for Parkinson`s Disease

Place: The auditorium in Bikuben, Jonas Lies vei 69 (campus Haukeland University Hospital)

Time: Wednesday February 15 at 11:30 - 13:00 (lunch from 11:30 - 12:00).

Abstract: Parkinson`s disease is a complex neurodegenerative disorder. Despite great efforts, the mechanisms leading to and propagating the disease are still far from understood. Clinical trials and studies are vital to gain insight in the disease and test new promising treatment regimens, however, they also come with challenges such as immense costs, long durations, and restricted sampling possibilities. Therefore, research using animal and cell models is essential to provide new insights and generate hypotheses that eventually can be tested in patients. While cell models are limited and not able to exactly replicate the complexity of the disease, they can be successfully applied to investigate distinct aspects of the disease, such as mitochondrial dysfunction or aberrant protein homeostasis. Several models exist, including genetic and pharmacological models, and employ different cell lines to represent different cell- and tissue types, depending on the research question. These cell models have several advantageous characteristics, such as basic maintenance requirements, reproducibility, versatility, and virtually limitless sample access. An overview of different model systems and approaches will be given, along with examples of the models used in our lab. 

Who: Open for all interested

Lecture language: English

ECTS: Participation provides ECTS for PhD candidates and is part of the Neuro-SysMed Graduate School of Translational Neuroscience. If you are a UiB student, make sure you register each term in Studentweb for the subject NEUROSYSM920 Neuro-Sysmed seminars and symposium.

Seminar coordinators: Cecilie Kristiansen and Sam Anandan.

Speaker: Ole-Bjørn Tysnes, Neuro-SysMed PI on the ALS field, senior consultant neurologist at the Department of Neurology, Haukeland University Hospital, and Professor at the University of Bergen.

Title: The NO-ALS study: the first Norwegian experimental treatment study against ALS

Place: The auditorium in Bikuben, Jonas Lies vei 69 (campus Haukeland University Hospital)

Time: Wednesday March 22 at 11:30 - 13:00 (lunch from 11:30 - 12:00).

Lecture language: English

Abstract: ALS has an annual incidence of 2-3 per 100,000. The disease is slightly more frequent in men than in women. Average survival from time of diagnosis is three years. There is no effective treatment. Riluzole has been available for a number of years but has very limited efficacy. There is therefore a great need for more effective treatment.

In 2020, the first patients were included in the NO-ALS study. This is a double-blinded randomized study in which patients are recruited from all over Norway. Motor neurons are energy-demanding cells. Mitochondrial failure has been demonstrated in these cells. In the NO-ALS study, treatment with Nicotinamide Riboside and Pterostilbene is attempted. The purpose is to try to increase mitochondrial access to NAD and thereby increase energy access to failing motor neurons.

Currently, almost 200 patients are included in the study, which runs over one year. The functional scale ALSFRS-R is the primary endpoint. There have been no serious side effects. The study has two arms, one for newly diagnosed patients and one for patients who have either had ALS over several years or who experience a slow development of symptoms.

It has been challenging to conduct a placebo-controlled ALS study. Many patients find it unreasonable to be at risk for receiving a placebo. Long travel distances to some of the study centres are also challenging. Over the course of one year, many patients become too ill to be followed up clinically at the study site. Based on this, the number of study centres has been expanded. The first results from the study will most likely be available within two years.

Speaker: Aurora Martinez

Title: Compound screening and drug discovery in Parkinson’s disease 

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital)

Time: Wednesday April 26 at 11:30 - 13:00 (lunch from 11:30 - 12:00).

Lecture language: English

Abstract: Computational and experimental screenings by specific assays and subsequent optimization of selected hits are crucial activities for the discovery and development of new drugs. In the field of Parkinson’s disease (PD) and other parkinsonisms, levodopa is considered the standard medication as it is relatively effective for the management of motor dysfunction, but often presents side effects and gradually loses efficacy. There are no effective disease modifying therapies that cure or slow down PD progression, and our research group aims to contribute to the development of these highly needed therapies. One of our main approaches focuses on the discovery of pharmacological chaperones, which are small molecular weight molecules that specifically bind to protein targets and stabilize unstable and misfolded conformations, with the potential to increase the half-life and functionality of the targets. We have developed biophysical and cellular high-throughput assays for the screening of chemical libraries with diversity-compound collections, fragments, or approved drugs for the identification of stabilizing binders, with follow-up functional assays and hit expansion and optimization. Understanding the structural and regulatory determinants of the targets and their complexes with regulatory proteins largely contributes to a successful development of mechanistic therapies. Results will be presented on our results on discovery and development of pharmacological chaperones for genetic conformational disorders, and to increase cellular levels of several targets of interest in PD, such as the highly regulated tyrosine hydroxylase (TH), the vesicular monoamine transporter 2 (VMAT2) and essential components of mitochondrial function, notably Complex I. 

Professor Alberto Ascherio from the Harvard T.H. Chan School of Public Health and Harvard Medical School, will present this years Falch Lecture: “The Epstein-Barr virus as the leading cause multiple sclerosis and the possible viral etiology of other neurodegenerative diseases”

The Faculty of Medicine and Neuro-SysMed are happy to invite you to this year’s Falch Lecture, presented by Professor Alberto Ascherio from the Harvard T.H. Chan School of Public Health and Harvard Medical School. You are also invited to an informal networking lunch before the lecture (lunch 11.30-12.00). No charge, just remember to register.

Title: "The Epstein-Barr virus as the leading cause multiple sclerosis and the possible viral etiology of other neurodegenerative diseases"

Time: Wednesday May 24, 11.30-13.00 (incl. mingling with lunch 11.30-12.00)

Place: The auditorium in Armauer Hansens Hus, Haukelandsveien 28, Bergen.

Professor Ascherio will review the data demonstrating that MS is a rare complication of infection with the Epstein-Barr virus (EBV), focusing on the recent investigation among over 10 million active-duty military personnel that provides virtually conclusive proof of causality. Further, he will briefly discuss the potential underlying mechanisms, and provide an epidemiological perspective on the potential role of infections in Alzheimer disease and other neurodegenerative conditions.

Ascherio is a Professor of Epidemiology and Nutrition at the Harvard T. H. Chan School of Public Health and a Professor of Medicine at the Harvard Medical School. Dr. Ascherio has focused much of his work over the past 25 years on discovering the causes of neurodegenerative diseases, including multiple sclerosis (MS), Parkinson disease, amyotrophic lateral sclerosis, and cognitive decline. He has conducted longitudinal studies in many populations, which have contributed to identifying several biomarkers and modifiable risk factors for MS (e.g. cigarette smoking, vitamin D insufficiency, and childhood obesity), Parkinson (pesticide exposure, low caffeine intake, low physical activity), and ALS (cigarette smoking, military service, low body mass index), and have in some cases provided the rationale for randomized trials (e.g. on physical activity in Parkinson disease). His most notable scientific contribution stems from the 20-year long investigation of over 10 million young adults that led to the recent breakthrough discovery that MS is a rare complication of infection with the Epstein-Barr virus.

Speaker: Gonzalo Sanchez Nido

Title: Decoding neurodegeneration - one cell at a time

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital)

Time: Wednesday June 21 at 11:30 - 13:00 (lunch from 11:30 - 12:00).

Lecture language: English

Abstract: Neurodegenerative diseases affect more than 100 million people worldwide and their prevalence is expected to double by 2050. With the vast majority of cases of the common neurodegenerative diseases being idiopathic, the lack of a mechanistic understanding of their pathogenesis represents one of the greatest challenges in neuroscience and public health. In order to shed light on the aetiology and pathogenesis of neurodegenerative disorders, a large number of next-generation sequencing-based studies of bulk brain tissue have attempted to nominate genes and pathways. However, due to the disease complexity and the unavoidable cellular heterogeneity of brain tissue samples, omic studies to date present contradictory and only partially overlapping results.

In this seminar I will discuss the impact of the inherent cell type variability of bulk-brain samples in the validity and interpretability of the results, especially in cases where cellularity is confounded with the disease status. To circumvent this limitation, we have resorted to single-cell RNA-sequencing to study the alpha-synuclein spectrum, an approach that holds the potential to differentiate between disease-specific regulatory changes and altered cell type and synaptic composition of the samples. I will present our latest results and elaborate on how such a high-resolution transcriptomic landscape can inform about pathological mechanisms and highlight potential biomarkers for neurodegenerative diseases.

Time: Friday September 1, 2023 at 12.00-13.30

Place: Auditorium 2 at the BB-building

Title of the talk: Metabolic Networks as Functional Biomarkers of Parkinson’s Disease

Coffee/tea will be available. All are welcome.

Speaker: David Eidelberg, MD, is head of the Center for Neurosciences at The Feinstein Institutes for Medical Research in Manhasset, New York. A neurologist and neuroscientist, he is widely known for his groundbreaking work on network dysfunction in neurological disorders including Parkinson’s disease, Huntington’s disease, dystonia and dementia.

He was first to identify metabolic networks as systems-level disease biomarkers in patients and has described previously unrecognized network pathologies. His automated computational approach is currently being used worldwide for the objective assessment of disease progression and treatment responses in individual patients and to enhance diagnostic accuracy.

His contributions have been recognized by the prestigious Fred Springer Award, the American Academy of Neurology Movement Disorders Research Award and the Bachmann Strauss Prize for Excellence in Dystonia. He is a member of the Association of American Physicians. Dr. Eidelberg received his medical training at Harvard, followed by postdoctoral fellowships at the National Hospital, Queen Square in London and Memorial Sloan Kettering Cancer Center in New York. He has authored more than 265 peer-reviewed original articles, 100 reviews and editorials, hundreds of scientific abstracts, and an edited volume (Imaging in Parkinson’s Disease, Oxford University Press, 2011). He serves on the editorial boards of several major journals and is editor-in-chief (Western Hemisphere) of Current Opinion in Neurology. 

Research focus: Dr. Eidelberg directs a leading imaging research program in brain disease. Under his direction, the Center for Neurosciences has been internationally recognized for his work on the identification, characterization and assessment of pathological brain networks using functional imaging techniques. Using innovative computational algorithms, he and his team have used disease networks as quantitative imaging biomarkers for the early diagnosis of neurodegenerative disorders such as Parkinson’s disease, Huntington’s disease and Alzheimer’s disease. His group is currently studying the effects of treatment on these networks in patients receiving novel interventions for the disorders.

Abstract of the talk: Network analysis of functional brain scans acquired with [18F]-fluorodeoxyglucose positron emission tomography (FDG PET, to map cerebral glucose metabolism), or resting-state functional magnetic resonance imaging (rs-fMRI, to map blood oxygen level-dependent brain activity) has increasingly been used to identify and validate reproducible circuit abnormalities associated with neurodegenerative disorders such as Parkinson’s disease (PD). In addition to serving as imaging markers of the underlying disease process, these networks can be used singly or in combination as an adjunct to clinical diagnosis and as a screening tool for therapeutics trials. Disease-specific networks can also be used to measure rates of progression in natural history studies and to assess responses to symptomatic treatment or to potential disease modifying agents. Recent imaging studies in PD subjects scanned before and after treatment have revealed therapeutic effects beyond the modulation of established disease networks. Rather, other mechanisms of action may be at play, such as the induction of novel functional brain networks directly by treatment. To date, reproducible treatment-induced networks have been reported for established interventions such as deep brain stimulation (DBS) and novel therapeutic strategies such as subthalamic gene therapy and oral nicotinamide riboside (NR), and as a potential imaging marker of the placebo response. Indeed, changes in the expression of these networks with treatment have been found to correlate consistently with clinical outcome. Together, the data suggest a role for functional brain networks as treatment biomarkers in clinical trials for PD and other brain disorders.

Speaker: Mathias Ziegler

Title: Key roles of NAD metabolism in neurodegeneration

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital)

Time: Wednesday September 13 at 11:30 - 13:00 (lunch from 11:30 - 12:00).

Lecture language: English

Who: All are welcome

Abstract: Rapid degeneration of an axon distal to an injury has been described in 1850 by A. Waller – and is therefore referred to as Wallerian degeneration. Only recently the mechanisms of this process have been identified. Instrumental to this achievement was the discovery of a mouse strain (WldS – Wallerian degeneration slow) that exhibits a substantially slower axon degeneration upon injury. Genetic analyses revealed that the delay in degeneration was caused by the triplication of a gene encoding an enzyme (NMNAT1) critical for NAD biosynthesis, thereby providing the first link between neurodegeneration and NAD metabolism. 

Recently, another key player in Wallerian degeneration was discovered to be SARM1. It turned out that SARM1 is a highly regulated NAD-cleaving enzyme. When activated, it can rapidly deplete intracellular NAD, thereby leading to cell (or axonal) death. Apparently, this is counteracted in WldS mice by enhancing NAD biosynthesis. Intriguingly, GWAS have indicated a linkage between ALS and the SARM1 locus.

Our recent work has established that SARM1 activity can be induced chemically in various cell lines indicating that mechanical injury is not necessarily required to trigger this pathway in axons. Moreover, we revealed that the SARM1-mediated cell death pathway is not unique for neurons, but rather wide-spread. However, it requires the presence of NMNAT2, an NAD biosynthetic enzyme highly expressed in the brain. The tools and cellular model systems we have generated will be valuable in further dissecting the mechanisms of Wallerian degeneration. Importantly, they will enable testing of therapeutic approaches to treat neurodegenerative diseases that may involve NAD- and SARM1-mediated cell death pathways.

Speaker: Professor Trond Riise

Topic: Registry – repurposing of drugs

Title: Drug-wide prospective study associates thirty-one drug classes with the risk of Parkinson’s disease

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital)

Time: Wednesday October 18 at 11:30 - 13:00 (lunch from 11:30 - 12:00).

Lecture language: English

Abstract:

The talk is based on the brand new publication Association Between the Use of Any of the Drugs Prescribed in Norway and the Subsequent Risk of Parkinson Disease; A Drug-wide Association Study, by authors Julia Romanowska, Kjetil Bjornevik, Marianna Cortese, Julia A. Tuominen, Magne Solheim, Asieh Abolpour Mofrad, Jannicke Igland, Clemens R. Scherzer and Trond Riise.

Background and Objectives: The incidence rate of Parkinson disease (PD) has been increasing rapidly during the past years. Yet, no treatments exist to prevent or slow the progression of the disease. Moreover, we are unable to detect early disease stages during which intervention with disease-modifying therapies is most likely to succeed. The objective of this study was to perform an agnostic drug-wide association study estimating the association between the use of any of the drugs prescribed in Norway and the subsequent risk of PD. 

Methods: This registry-based cohort study use data from the entire Norwegian population between 2004 and 2019 linked to the Norwegian Prescription Registry, with more than 600 million individual prescriptions. Drug classes were screened according to Anatomical Therapeutic Chemical codes at level 2, corresponding to therapeutic subgroups. We used Cox regression models to estimate hazard ratios (HRs) and 95% CIs for the associations between drug classes and PD risk. All p values were corrected for multiple testing using the false discovery rate. In addition, we conducted sensitivity analyses of exposure definition as well as time-lag and dose-response analyses. 

Results: The study population comprised 3,223,672 individuals, 15,849 of whom developed PD during the follow-up. We identified 31 drug classes that were statistically significantly associated with PD risk in Norway during the follow-up. Drugs acting on the renin-angiotensin system (HR 0.92, 95% CI 0.89–0.95), corticosteroids for systemic use (0.88, 95% CI 0.84–0.93), and vaccines (0.89, 95% CI 0.82–0.96) were associated with a decreased risk of PD even up to 10 years before PD onset. Drug classes used to treat symptoms related to prodromal signs of PD, such as constipation, urological issues, and depression, were associated with an increased risk of subsequent diagnosis of PD with HRs of 1.6 (95% CI 1.49–1.73), 1.48 (1.42–1.53), and 1.94 (1.87–2.01), respectively. 

Discussion: This drug-wide study identified 31 drug classes that were associated with the PD risk change. It reveals the links of renin-angiotensin system medications, vaccines, and corticosteroids with PD risk and suggests that monitoring drug usage using pharmacoepidemiology may allow identifying individuals with prodromal PD. 

Speaker: Dr. Christopher Elnan Kvistad

Christopher Elnan Kvistad is a neurologist and PhD. He has a postdoc in treatment with mesenchymal stem cells in MS, is PI in the SMART-MS study and a clinical career stipend from Helse Vest within the field of stem cell based neuroregeneration. 

Title: A brief history of the (failing) neural regeneration in the human CNS

Abstract: The failure of axons to regenerate is a major obstacle for functional recovery following CNS injury from various etiologies. Why is this? What has research shown us and what is the status today? The following lecture will try to answer these questions in a brief recapitulation of the research progress from 1600 BC until today.  

Chair: Professor Kjell-Morten Myhr

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday November 22 at 11:30–13:00 (lunch 11:30–12:00).

Speaker: Professor Mathias Toft from the University of Oslo / Oslo University Hospital

Title: "Insights into Parkinson's disease: From genetic associations to functional mechanisms"

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital, Bergen)

Time: Wednesday December 13 at 11:30–13:00 (lunch 11:30–12:00).

Abstract: Genome-Wide Association Studies (GWAS) have elucidated the genetic components of Parkinson's disease (PD). However, translating these results into an interpretable, mechanistic understanding of the disease etiology remains a major challenge in the field. In this presentation, I will provide an overview of our approaches to prioritize putative causal genetic variants. The results of studies of polygenic risk scores and the relationships to clinical traits will be discussed. Further, the results of recent transcriptomic and epigenetic studies will be presented, focusing on how these findings can be translated for clinical applications. 

Mathias Toft is Head of the Department of Neurology, Oslo University Hospital and Professor of neurology at the University of Oslo. Prof. Toft is a clinical neurologist and researcher specialized neurodegenerative disorders, in particular studies of Parkinson’s disease. He studied medicine at the University of Tübingen, Germany. His doctoral degree from NTNU was focused on genetic studies of Parkinson’s disease, and the majority of the studies were carried out at the Mayo Clinic in the United States. More recently he has performed clinical and genomic studies of movement disorders. He is currently leader of the research group Movement disorders and Neurodegeneration.

Chair: Professor Charalampos Tzoulis