Projects
Mitochondrial imaging in live neurons from Parkinson’s disease patients. KU Leuven
Parkinson’s disease is the most prevalent neurodegenerative movement disorder. These patients suffer from characteristic motor problems, but can also develop a variety of non-motor problems such as constipation, psychosis, depression and dementia, all of which severely undermine quality of life. A typical characteristic of Parkinson’s disease is the loss of a specific population of nerve cells that produce dopamine in a brain region called ...
Longitudinal measurement of synaptic density to monitor progression of Parkinson's disease and Huntington's disease KU Leuven
Increasing evidence from cell or animal models and postmortem human studies suggests that synaptic pathology is important in the early disease pathophysiology of Parkinson’s (PD) and Huntington’s disease (HD). PET imaging with 11C‑UCB‑J, targeting the presynaptic protein SV2A, provides an in vivo marker for synaptic density in the human brain. This thesis reports two multimodal imaging studies in people with early PD and early HD ...
Molecular mechanisms of GCH1-associated Parkinson's disease. KU Leuven
GCH1 mutations are a known cause of dopamine-responsive dystonia. GCH1 mutations lead to reduced levels of tetrahydrobiopterin (BH4), an important cofactor in the dopamine synthesis pathway. BH4 also exhibits anti-oxidative properties. Very recently, a new link was discovered between GCH1 mutations and the risk of Parkinson´s disease. My research project focuses on unraveling the mechanisms by which GCH1 mutations predispose to nigrostriatal ...
Analysis of mitophagy in patients with idiopathic and monogenic Parkinson’s disease KU Leuven
Parkinson disease (PD) is a disabling, incurable disorder with increasing prevalence in the western world. In rare cases PD is caused by mutations in the genes for PINK1 (PTEN induced kinase 1) or PRKN (E3 ubiquitin-protein ligase parkin), which impair the selective autophagic elimination of damaged mitochondria (mitophagy). Mutations in the gene encoding LRRK2 (leucine-rich repeat kinase 2) are the most common monogenic cause of PD. Here, we ...
Prospective head-to-head comparison of cardiac [18F]-MFBG PET versus [123I]-MIBG SPECT in the differentiation between Parkinson’s disease and multiple system atrophy and between dementia with Lewy bodies and Alzheimer’s disease. KU Leuven
The present study will be sponsored by the KU Leuven with Koen Van Laere, Prof MD PhD DSc, as its principal investigator. The purpose is a prospective head-to-head comparison of [18F]-MFBG cardiac innervation in the differential diagnosis of Parkinson’s disease and dementia with Lewy Bodies, compared to cardiac innervation measured by [123I]-MIBG cardiac imaging and brain dopamine transporter availability measured by [18F]-PE2I PE. Primary ...
[18F]-MFBG PET of the cardiac noradrenergic system for early differentiation in Parkinson’s disease and dementia with Lewy bodies. KU Leuven
The main aim of this project is to validate and optimize the clinical use, leading to reimbursement of recently introduced cardiac [18F]-MFBG noradrenergic transporter (NET) Positron Emission Tomography (PET) in the diagnostic workup of patients with suspected neurodegeneration, both movement disorders (differential diagnosis between Parkinson’s Disease (PD) and the parkinsonian variant of Multiple System Atrophy (MSA-P)) and two of the most ...
Analysis of the effect of LRRK2 mutations on mitophagy in iPSC-derived neurons from people with Parkinson’s disease KU Leuven
Parkinson’s disease (PD) is a highly disabling neurodegenerative disorder for which no disease-modifying therapies exist yet. Development of such treatments is hampered by lack of insight into the pathogenic pathways underlying PD. A number of different monogenic causes of PD have been identified. Loss-of-function mutations in the genes for PINK1, parkin and DJ-1 cause autosomal recessive PD and disrupt mitophagy, a form of selective ...
Translational Markers for Precision Medicine in Modifying Parkinson's Disease KU Leuven
This doctoral project, in collaboration with Janssen Pharmaceutica and Verstreken Lab at VIB-KU Leuven, contributes to the improvement of the prevention, diagnosis, and treatment of Parkinson's Disease. Today, there is an urgent need to shift the classical focus on symptomatic relief towards the modification of the initiation and progression of α-synucleinopathy leading to Parkinson's Disease. In this project, preformed α-Synuclein fibrils ...
Analysis of the effect of the Parkinson’s disease-linked VPS35 mutation on mitophagy KU Leuven
Parkinson’s disease (PD) is the most common neurodegenerative movement disorder with a strongly increasing prevalence. No cure for PD exists yet. Therefore, it is important to further elucidate the pathogenic mechanisms of PD. A minority of PD cases have a monogenic cause. VPS35, LRRK2 and SNCA are genes linked to autosomal dominant PD. VPS35 is part of the retromer complex, which mediates the retrograde transport of proteins from the ...