Promising step
Rik van der Kant discovered that cholesterol buildup in brain cells of Alzheimer’s patients directly leads to an accumulation of the toxic proteins Tau and Amyloid. He also found that Efavirenz might be suitable for reversing this buildup. Dr. Jort Vijverberg, Neurologist at the Alzheimer Center is also hopeful about the trial “We are very curious to see how this medication will work in Alzheimer’s patients, I consider it a promising step in the right direction.”
Participants needed
The trial is still looking for participants. In total, forty patients are needed to take part in the three-month clinical trial in Amsterdam. Participants can take part if they have been diagnosed with early-stage Alzheimer’s disease, are between 50 and 75 years old, and have a family member or caregiver who can accompany them to the research center visits and answer questions about their health and daily functioning. If participants are unsure whether they want to or are able to take part, they can always register without obligation. Their eligibility to participate will be assessed at a later stage.”
For more information, visit Efavirenz – Brain Research Center
Schizophrenia and height are both associated with, among other things, hormonal imbalance, brain size, socioeconomic status, infections and nutrition. Neuroscientist Cato Romero and his colleagues therefore investigated which biological processes schizophrenia and height have in common, to see whether this overlap can provide more information about how schizophrenia develops. The study was published in Biological Psychiatry
The study by Romero et al. used data from large datasets of hundreds of thousands of participants to compare the genetic variation associated with schizophrenia with the genetic variation associated with height. By analyzing DNA variation, they identified genetic markers that relate to both.
Thyroid hormones and immune response
The researchers discovered 142 genes that were linked to both schizophrenia and height. The shared genes showed high expression in the pituitary gland, a small organ that secretes several essential hormones. Within the pituitary, one type of cell, the thyrotrope, stood out in the findings: thyrotropes produce thyroid-stimulating hormone, which regulates the level of thyroid hormones in the body.
In addition, many of the shared genes are involved in the immune response. A large number of genes are active in white blood cells, which help the body fight infection. A link between increased inflammation and schizophrenia has previously been found. It is possible be that the body spends more energy on recovering from infections and therefore less on growth.
Diversity in genetic studies
A caveat to the study is that the evidence for these findings was less robust in datasets from non-European people. This is partly due to the fact that non-European datasets are currently still significantly smaller. According to Romero, there is therefore a need to increase diversity in genetic studies.
For now, this new knowledge about shared genetic mechanisms inspires further research into the exact relation between schizophrenia on the one hand and immune responses and thyroid hormone on the other.
The article can be found here:
https://www.sciencedirect.com/science/article/pii/S1074742725000140?via%3Dihub
In this article, the authors performed closer investigation of so-called engram cells which are thought to harbor the physical representation of memories. While numerous engram cells across the brain are activated during memory formation, only a subset is reactivated during recall. In this project, the authors investigated whether structural synaptic connectivity of these reactivated and non-reactivated engram cells differs in the hippocampus and whether this is dependent on the context valence. To achieve this, a novel analysis pipeline was developed that enables semi-automatic reconstruction of spines and dendrites based on fluorescent labelling of engram cells. The pipeline also integrates multilevel statistical analyses to account for the nested data structure. The authors found that at the level of excitatory CA3 to CA1 engram cells, structural synaptic connectivity of CA1 engram cells is influenced by contextual valence, reactivation status of an engram cell, or a combination thereof. Specifically, parameters related to the number, distribution, and morphology of CA1 engram cell synapses vary based on these factors. These findings give first indications that engram cells follow distinct pathways in structural synaptic connectivity, which may be essential for refining and sustaining engram networks over time.
The analysis pipeline is accessible on GitHub under the following link:
https://github.com/PantheaNemat/structural_dendrite_spine_analysis
Research shows that drugs targeting genes identified in genetic studies are 2.3 times more likely to receive FDA approval than those without such genetic evidence. However, determining which genes are truly causal for disease remains a major challenge.
Now, researchers Marijn Schipper and Danielle Posthuma from the Complex Trait Genetics lab at CNCR have introduced FLAMES, a machine-learning tool designed to improve gene prioritization based on genetic discovery studies. Their study, published in Nature Genetics highlights how FLAMES outperforms existing methods by combining multiple approaches and large-scale genetic data to make more accurate predictions.
FLAMES was used to find schizophrenia-related genes, successfully prioritizing 180 genes from 255 known genetic regions. These genes were found to be linked to synaptic function and divided into two key groups: one related to early brain development and the other to processes occurring later in life.
As part of the BRAINSCAPES consortium, Professor Posthuma plans to apply FLAMES to uncover new insights into brain disorders. The tool is currently being used to study genes involved in alcohol addiction, anxiety, depression, insomnia, and Alzheimer’s disease.
FLAMES is freely available, allowing researchers worldwide to prioritize genes for any disease or trait with genetic data, opening new doors for medical breakthroughs.
With the title of his inaugural lecture ‘Faltering nerve cells, from defective communication to recovery from brain diseases’ Ruud Toonen has been appointed as Professor of Neuroscience and Knowledge Utilization at VU Amsterdam. In his oration, Ruud Toonen discusses how advanced technologies can be used to treat brain diseases more effectively.
Disrupted communication between nerve cells is at the root of many brain diseases. Complex nanomachines control the release of signaling substances for nerve cell communication. Genetic defects can disrupt these processes, leading to severe brain disorders with major consequences for patients, their families, and society.
With advanced technology, skin cells from patients are converted into nerve cells without the need for a brain biopsy. In the laboratory, these cells grow into networks on which, together with pharmaceutical companies, innovative therapies are being tested. These promising treatments are about to be used in clinical trials. This approach applies to a variety of brain disorders. The goal is to accelerate therapies and improve patient well-being.
About Ruud Toonen
To process information the brain is constantly changing the strength of the individual contacts (synapses) between nerve cells. Strict control of synaptic plasticity is important, as dysregulation is often associated with neurological disorders.
The lab of Ruud Toonen studies the mechanisms that support synaptic plasticity and their dysfunction in disorders such as Alzheimer’s, epilepsy, schizophrenia and autism to provide novel treatment options and therapeutic targets. They study the presynaptic mechanisms of synaptic plasticity and secretory vesicle dynamics and release. Ruud Toonen has several coordinating tasks for the Fundamental Neuroscience track in the second year of the Research Master Neuroscience, the Minor Biomolecular and Neurosciences track Neuroscience, and the Master courses Live Cell Imaging and Developmental Neuroscience. In addition, he is a member of the Master of Neurocience education committee and the ONWAR PhD teaching committee.
The Dutch Research Council (NWO) has awarded a 3.1 million€ ENW-XL grant to the SUPERGLUE consortium lead by Mark Verheijen (CNCR-MCN) and Rogier Min (AUMC), together with Piyanka Rao-Ruiz (CNCR-MCN), Harold MacGillavry (CNCR-MCN), Natalia Goriounova (CNCR-INF), Erik Bakker (AUMC), and Elga de Vries (AUMC).
Research on information processing in the brain previously focused mainly on communication between neurons. However, in recent years it has emerged that a non-neuronal cell, the astrocyte, which was previously seen as a kind of support cell of your brain, also plays a role in memory and cognition. Astrocytes do this by forming connections with both neurons and blood vessels in the brain. Which molecules are involved in these connections is largely unknown. In SUPERGLUE the researchers use advanced techniques to map these molecules and cellular interactions, taking an important step in our understanding of information processing by the brain.
THE VALUE OF FUNDAMENTAL RESEARCH: The NWO-XL research consortia do share one common and essential goal: to take a big step in the direction of curiosity-driven research by consortia. The Open Competition NWO-XL is essential for the sciences as the only instrument for fundamental collaboration.
With this funding, it is up to the researchers to start, strengthen or expand groundbreaking and innovative world-class research lines together. The value of fundamental research: ‘Many of the results of fundamental research eventually end up in society. You just don’t know in advance how and when.. Without fundamental research, there is no foundation to build on.’
With this 400 000 euro support by Alzheimer Nederland, the van Weering lab will aim to restore synaptic connectivity in human neurons that accumulate intracellular tau aggregates, that resemble tau pathology found in neurodegenerative disorders such as Alzheimer’s disease and frontotemporal dementia. Using an integrated approach of imaging, electron microscopy and biochemistry, his team will assess how trophic and metabolic signaling can be utilized to prevent the loss of neuronal connections under tau pathology conditions.
There will be a PhD position opening at the secretory vesicle trafficking and recycling team (see lab website).
Perspectives on Knowledge Utilization in Life Sciences
January 31, 2025
Theater 8, Rialto/VU (NU-4C47, De Boelelaan 1111, Amsterdam)
Knowledge utilization in the Life Sciences is vital to the improvement of healthcare outcomes, to address global challenges like public health and environmental sustainability, and also for advancing scientific research itself. By effectively applying their scientific discoveries, scientists can have tremendous impact, but the inroads towards effective knowledge utilization are complex and diverse. This symposium showcases different successful strategies for knowledge utilization in the life sciences, using different organizational structures inside and outside academia, different ways of exploiting and protecting intellectual property and different approaches to raising funds. With these insights the symposium aims to inspire future knowledge utilization, finding the optimal solution for each unique opportunity, exploiting the full potential of scientific advancements in the life sciences sector and producing tangible benefits for a healthier, more sustainable future. The symposium is free and open to the public, targeting students, life science professionals, and individuals working in the medtech and biotech sector. Registration is not required.
Program:
13:00 – 13:10: Introduction
Prof. dr. Iwan de Esch, vice Dean of Valorization, Science Faculty VU
13:10 – 13:30: Avengers assemble: uniting academia, industry, and regulators to bring novel treatments for rare diseases
Dr. Andrea Soto Padilla, Business Development Manager at Amsterdam UMC
13:40 – 14:00: The role of venture capital in bringing new treatments to patients
Dr. Cillian King, Managing Director EQT Life Sciences
14:10 – 14:30: Tumor Infiltrating Lymphocyte (TIL) therapy for the treatment of patients with advanced melanoma: from an academic phase III trial to marketing authorization and sustained patient access for an affordable price.
Dr. Inge Jedema, head of Translational Cellular Therapy NKI
14:40 – 15:00: Bridging academia & industry: accelerating drug development for neurological disorders
Dr. Claudia Persoon, co-founder and CEO of Neurospector
The symposium precedes the inauguration lecture of Dr. Ruud Toonen, professor of Neuroscience and Knowledge Utilization, entitled: Faltering nerve cells, from defective communication to recovery from brain diseases. The lecture starts at 15:45 in the aula op de VU University (VU main building, De Boelelaan 1105, Amsterdam) and is open to the public.
Speakers:
Prof. dr. Iwan de Esch is professor in Drug Design & Synthesis and director of valorization at the Faculty of Science, VU University. Iwan obtained his PhD at VU University and received postdoctoral training at the University of Cambridge. Iwan participated in many large national and EU projects for Top Institute Pharma, STW, FP7, ITN and IMI. Iwan is the co-founder of three academic spin-out companies: De Novo Pharmaceuticals Ltd (a spin-out of the University of Cambridge), IOTA Pharmaceuticals Ltd and Griffin Discoveries BV (the latter two spun-out of VU University). As director of valorization, Iwan aims to stimulate a wide variety of valorization activities within the Faculty of Science.
Dr. Andrea Soto Padilla is a Business Development Manager at Amsterdam UMC. Andrea started her career as a scientist in neurodegeneration and social behavior research. After her time in academia, Andrea worked as a consultant for biotech firms, helping them develop their business plans and secure funding. A few years later, she became an Associate at EQT Life Sciences to build their Dementia Fund. Through this work, she met and later joined Amsterdam Neuroscience as a Business Developer to help push academic innovations into real-life solutions. Andrea is also executive board member of ESCO, a European consortium that prepares for trial readiness for a rare neurodevelopmental disease.
Dr. Cillian King is a Partner at the venture capital firm EQT Life Sciences. Before EQT, Cillian worked as an Investment Manager for Life Science Partners and Swanbridge Capital and as an independent consultant for early-stage bio/medtech companies. Cillian obtained his PhD in molecular neuroscience at CNCR, VU University. Cillian has been a major catalyst in translating academic discoveries into business opportunities by data-driven decision-making, designing investment strategies and promoting sustainable growth. Cillian is known for connecting stakeholders, from investors and private companies to academic institutions and individual scientists.
Dr. Inge Jedema is head of Translational Cellular Therapy at The Netherlands Cancer Institute. Until 2020, Inge was head of the laboratory for Translational Hematology at Leiden UMC and developed several cellular immunotherapy strategies and clinical trials. Most recently Inge and her colleagues became nationally known for developing a treatment for metastatic skin cancer without the help of commercial investors. The project is unique in that it was all funded publicly (ZonMW, KWF, EU). If the team obtains approval from the EMA, it will be the first time that an academic hospital brings a complex cell therapy to the market. Because the therapeutic product will be offered via a not for profit model, the treatment is approximately five times cheaper than a comparable commercial therapy.
Dr. Claudia Persoon is co-founder and CEO of Neurospector, a contract research organization within the university that accelerates drug development for psychiatric and neurological disorders by combining the use of human (patient-derived) neurons and scale-able functional assays. Claudia studied life sciences in Amsterdam and obtained her PhD in cellular neurosciences at CNCR, VU University. Claudia received entrepreneurship training at Ace Incubator where she won a scholarship for best business plan and obtained several spin-out grants (NWO take-off, ERC-PoC) to establish Neurospector. Neurospector is a unique new solution for knowledge utilization by VU and Amsterdam UMC employers.
The grant of 850 000 euro will allow her to expand her research team to further investigate how changes in neuronal activity differentially affects AIS composition in excitatory and inhibitory neurons, and how this differential plasticity participates in network homeostasis during sensory-dependent experience.
This project will use proteomics and transcriptomics approaches in cultured neurons and in vivo, coupled to super-resolution imaging and electrophysiology.
There will be PhD and post-doc positions opening in the AIS lab (see lab website: https://cncr.nl/research-team/axon_initial_segment_biology/)
More information on awarded Vidi projects can be found here.
The awarded project, titled “Should I stay or should I go? Elucidating neuropeptidergic modulation of approach-avoidance behaviour” focuses on the neurobiological mechanisms that control our responses to challenging environments. In particular, Danai’s team will work on identifying how neuromodulators, such as norepinephrine and various neuropeptides, mediate behavioural choices during negative (stressful or threatening) experiences.
Taking advantage of a multilevel approach, that includes synaptic proteomics, electrophysiology and circuit manipulation in the behaving animal, Danai aims to highlight the endogenous systems that promote adaptive stress responses and prevent maladaptations linked to the development of psychopathology, inlcuding anxiety, impulse control and attentional disorders.
See the research team page for more information.