Sigrid Jusélius Foundation has granted a senior researcher post to Docent Šárka Lehtonen from the University of Eastern Finland. Her lab develops novel human-based models to study the mechanisms of Parkinson’s disease and other neurological diseases.
The senior researcher post is awarded for a period of three years and also covers the cost of research materials. The total amount granted is 500,000 €. The foundation supports and promotes medical research to combat diseases that are devastating to humankind.
Lehtonen's lab focus has been to reveal the cellular and molecular mechanisms of neurological diseases, especially Parkinson`s disease (PD). “We use patient-derived brain cells in 2D and 3D culture systems to mimic the pathological conditions in the diseased brain more accurately,” says Lehtonen.
Parkinson’s disease is a multisystem neurodegenerative disorder with no disease-modifying therapy available. Familial PD is caused by gene mutations, which account for about 10% of PD cases, and shares some clinical features with sporadic PD. Sporadic PD is primarily a disease of aging; however, not everyone develops the disease, and the mechanism is still unknown.
The induced pluripotent stem cells can be used nowadays to model both familiar and sporadic PD in the early stages of the disease. Still, adequate animal models are needed to assess the behavior, especially motoric skills, when the disease progresses. Humanized rodent models where the human cells of interest are transplanted into newborn mice brain allow researchers to investigate cellular interactions in the complexity of the living brain and in response to triggered pathology in addition to performing behavior studies.
Lehtonen's lab plans to use human microglia and astrocytes from healthy and PD donors for transplantation and trigger the pathology by human alpha-synuclein fibrils to bridge the gap between animal and human cell culture models. “We anticipate that gained knowledge from novel human cell-based models can, in the future, be used to stop disease initiation, slow progression, or reverse the effect of neurodegeneration,” comments Lehtonen.
The lab is also interested in building up a human organ-on-chip model for the blood-brain barrier (BBB) as the BBB and drugs' ability to cross the BBB and reach the correct target is critical when designing drugs for neurological diseases. They are building up the model with multiple human cell types essential for BBB in a custom-designed microphysiological system provided by Finnadvance – an Oulu-based startup company. Such a model mimics the physiological architecture and the barrier properties and will be used for testing the novel drugs and biomolecules like extracellular vesicles to penetrate the BBB. The model can also be used to uncover the molecular and transport mechanisms that regulate BBB permeability in physiological and pathological conditions.