New Woelse Waard grant for Elly Hol: reactive gliosis in Parkinson’s Disease
Unravelling the role of glial cells in brain disease
Glial cells are crucial for brain function, providing essential support to neurons, yet they remain understudied in the context of brain diseases. When an inflammatory response known as ‘reactive gliosis’ occurs, these cells may lose their neuron-supportive functions and contribute to disease onset. A research team from UMC Utrecht, led by Professor Elly Hol, has secured a Woelse Waard grant to study glial cells in the context of Parkinson’s Disease.
Parkinson’s Disease (PD) is a neurodegenerative brain disease in which midbrain dopaminergic neurons, necessary for coordinating movement, gradually degenerate. The new research project, dubbed ‘GliaPark’, strives to uncover how glia are involved. This is a crucial stepping stone to developing therapeutics to halt this neurodegenerative process and utilizing glial cells as a new target in PD and other brain diseases.
Targeting astrocytes
One specific type of glial cell is the astrocyte. In PD, astrocytes have been significantly less researched than dopaminergic neurons. Elly Hol, professor of Glia biology of brain diseases, explains: “Astrocytes are known to undergo reactive gliosis in PD. The change in astrocytes will contribute to neurodegeneration and can lead to an early loss of dopaminergic neurons. Therefore, targeting astrocytes might help to prevent neuron loss.”
Organoids
The new study is spearheaded by Elly Hol. She will carry out the project together with Translational Neuroscience researchers Jeroen Pasterkamp, Frank Meye, and PhD student Hanne Twenhöfel, alongside a patient researcher from the Parkinson’s Association. The team will use in vitro models derived from Parkinson’s patients to examine how these cells behave under reactive gliosis conditions, aiming to shed new light on neurodegenerative mechanisms and potential therapeutic strategies.
To achieve this, the researchers will create 2D and 3D co-culture models using human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons and astrocytes, incorporating varying PD mutations. They will then assess differences in cell activity, reactive gliosis, morphology, neuropathology, and RNA expression across these cultures and controls.
Deeper insights
Ultimately, the researchers want to create assembloids: interconnected midbrain and striatum organoids (implementing a protocol by Jürgen Knoblich). The midbrain is normally connected to the striatum, providing dopaminergic input for movement control. In PD, when midbrain dopaminergic neurons degenerate, the striatum loses that input. With these assembloids, the team can investigate how a PD midbrain organoid affects a control striatum organoid, and vice versa, to gain deeper insights into neurodegenerative processes.
Follow-up project
In the next few years, Elly plans to initiate a follow-up project to expand upon the results found and, wherever possible, to conduct valorization by working together with a company on possible further development of medication targeting astrocytes. By uncovering how astrocytes contribute to neurodegeneration, these studies could lay the groundwork for new therapies for PD and potentially other brain diseases.
Consortia
Among the researchers, there are strong interactions with the following consortium projects: the BrainScapes program (gravity subsidy – dopaminergic system), spanning the VU, Amsterdam UMC, LUMC, and TU Delft; and MODEM (dementia program ZonMW – neuron-glia interactions), spanning the VU, Amsterdam UMC, LUMC, TU Delft, Radboud UMC, UMCG, and MUMC.
Vrienden UMC Utrecht & Wilhelmina Kinderziekenhuis
This research project is made possible thanks to the support granted by Stichting Woelse Waard to Stichting Vrienden UMC Utrecht & Wilhelmina Children’s Hospital, the charity of the (children’s) hospital. If you would like to contribute to our research, please contact Stichting Vrienden by phone at 088 756 10 10, or go to https://vriendenumcutrecht-wkz.nl/.
Elly Hol secures BRAINS grant to investigate reactive gliosis in various brain diseases
New research into glial cells’ role in brain disease
Research into brain diseases frequently concentrates on neurons, yet they might only reveal part of the story. Rather, the helper cells known as glia could hold the answers to the disrupted neuronal communication seen in numerous brain diseases. Specifically, a disease-induced state of glia known as reactive gliosis is suspected to be a key factor in disease onset and progression. Now, a new BRAINS grant will support a four-year study into the behavior of glial cells in various brain diseases such as Alzheimer’s disease, MS, epilepsy, ALS and other neurological disorders.
The GLIODEM BRAINS project will see top Dutch glia biologists and neuroscientists partner with Swiss biotech company GliaPharm to deliver new insights. The project aims to uncover the consequences of reactive gliosis on neuronal functioning using human in vitro models. This collaborative effort combines academic expertise and industry innovation to advance our understanding of brain diseases, potentially paving the way for innovative treatments targeting glia.
Ameliorate gliosis
Translational Neuroscience researchers Prof. dr. Elly Hol, Prof. dr. Jeroen Pasterkamp, Dr. Frank Meye, Dr. Christiaan Huffels, Dr. Elena Daoutsali, Laura Pieper and new PhD student Arthur Ermakov will collaborate with GliaPharm to measure changes in neuron-glia interaction in human iPSC and organoid models. They will develop new readouts and test novel pharmacological and genetic approaches to ameliorate reactive gliosis.
The models used in the project include both astrocytes and microglia, providing a clearer, more relevant picture of how cell types interact and cause network-wide effects in conditions of stress and toxicity.
“Previously, most brain research focused on neurons in brain disease, says Hol. “Fortunately, more and more attention is now being paid to the behavior of glial cells, which offers new opportunities for drug development. In our lab, a team is working on innovative techniques to better study gliosis. Together with GliaPharm, we will research new medicines that specifically target gliosis, with the aim of better treating people with brain diseases in the future. We are very pleased with the funding from BRAINS, which makes this collaboration possible.”
GliaPharm’s scientific founder Prof. Pierre Magistretti adds:
“This international collaboration blends unique academic and industrial expertise. Together, we aim to develop innovative models that mimic the fundamental dysfunctions of glial cells in various neurological diseases. These models will be crucial for creating novel therapies that specifically target glial cells, opening new horizons in the treatment of these conditions”.
To read more about the innovation inherent to this project, go here. Stay tuned for upcoming GLIODEM developments!
About BRAINS
The BRAINS partnership is a joint grant opportunity in which the following health funds join forces: Alzheimer Nederland, Stichting MS Research, EpilepsieNL and Hersenstichting.
BRAINS originated from the Netherlands Brain Initiative (Nationaal Plan Hoofdzaken), a movement dedicated to creating solutions for individuals with brain and/or psychological disorders. The Netherlands Brain Initiative achieves this by fostering connections across various disciplines and collaborating with other organizations.
This collaborative BRAINS project has been co-financed with a PPS grant provided by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships.
For more information about Health~Holland and the Netherlands Brain Initiative, please visit www.health-holland.com and www.nationaalplanhoofdzaken.nl.
About GLIAPHARM
GliaPharm is a Swiss biotech company that develops innovative approaches to treat neurological and psychiatric disorders. GliaPharm was created in 2016 as a spinoff company from the laboratory of Prof. Pierre Magistretti at the Swiss federal institute of technology (EPFL, Switzerland), a leading research laboratory in the field of brain metabolism and glial cell biology. GliaPharm has established a pipeline of compounds through its in-house proprietary drug discovery platform focused on glial cell function. These compounds aim at promoting brain energy metabolism by specifically targeting glial cells.
ENW-M-2 grant for Heidi Lesscher and Frank Meye on risky play and stress resilience
New ENW-M-2 grant for our researchers! Recently the NWO Domain Board Science approved twenty-six grant applications in the Open Competition Domain Science-M programme. One of these grants was awarded to Heidi Lesscher (PHS, DWM) and Frank Meye (Translational Neuroscience, UMC Utrecht) to study if early life play opportunity, and in particular ‘risky’ play, promotes the development of cognitive control and stress resilience in later life. In this project, rats experiencing different degrees of play during early life will be compared for their degree of cognitive control under stress. Expectations are that enhanced opportunities for risky social play in early life enhance stress resilience in later life. We will also address the neurobiological effects of social play on cognitive control networks. Understanding how play shapes stress resilience is important for the prevention of mental health problems. Stay tuned for positions opening up related to this project.
“Very excited to team up with Heidi Lesscher to unravel if early life risky play opportunities alter neural networks of cognitive control to confer stress resilience in later life” Frank Meye
This research will in part be carried out at our Translational Neuroscience Department, as part of the UMC Utrecht Brain Center.
XS grant for Danai Riga
Post-doc researcher Danai Riga investigates ways to raise our body’s defends against stress, in order to prevent the development of anxiety. In particular, she aims to understand how built-in anti-stress systems work, and how to harness their therapeutic potential to alleviate anxiety. She received an XS grant (50.000 euro), via the NWO’s Open Competition Domain Science, which supports the fast implementation of curiosity-driven, groundbreaking ideas. Her project, titled “Stamps of resilience: elucidating the molecular diversity of the brain’s anti-stress system”, will examine the unique molecular identity of neuronal cells that mediate stress-relief.
“I am honoured to have received the XS grant, which will help me realise an exciting set of experiments in collaboration with other researchers of the Brain Center. Together, we will provide a detailed molecular map of our brain’s anti-stress system. We hope this will form the basis for uncovering novel targets for the treatment of anxiety”
She will perform the described work at the Translational Neuroscience department together with Frank Meye and colleagues.
Congratulations!! 🎊👏
Vidi grant for Frank Meye
Assistant professor Frank Meye researches how stress alters the strength of connections in the brain involved in decision-making, and how this can lead to impulsive eating behavior. He also investigates how this process can be turned for the better by targeted manipulation of brain activity.
He has received the prestigious VIDI grant (800,000 euro), titled “The need to eat: Why stress makes you crave junk food “, to facilitate his research at our Translational Neuroscience Department.
“This Vidi grant plays a crucial role in further forming my research group that aims to understand how stress leads to plastic changes in the brain, and how this plays a role in multiple disease processes. It’s great that this application has been granted, as our lab is very excited to take on the challenge of better understanding these important processes!” Frank Meye
External links:
https://www.umcutrecht.nl/en/about-us/news/details/seven-vidi-grants-awarded-to-umc-utrecht
https://www.nwo.nl/en/researchprogrammes/nwo-talent-programme/projects-vidi/vidi-2020