Inhibiting Acute Episodic Neurological Decline in Vanishing White Matter

at  Amsterdam UMC

ABOUT THE PROJECT

Research in the Amsterdam Leukodystrophy Center aims at improving insight into leukodystrophies and developing treatment. The disease “vanishing white matter” (VWM) has been a major research focus since long. VWM mostly affects children. We defined this disease 30 years ago and identified the related genes in 2001. VWM is characterized by chronic progressive neurological decline, in which patients lose neurological functions, become wheelchair-bound and die. Brain MRIs reveal increasing brain white matter abnormalities that never improve. Additionally, physical stresses, such as fever and infections, can provoke acute episodes of neurological decline, in which VWM patients show rapid neurological deterioration, often with lowered consciousness. Sometimes death follows, but often partial and in few cases complete recovery occurs. These acute episodes worsen overall disease progression with earlier death. With growing insight into disease mechanisms underlying chronic neurological decline, several therapeutic interventions have been developed and tested with promising results. This project aims at investigating acute episodic neurological decline, including underlying mechanisms, and exploring ways to mitigate it.

PROFILE

We are looking for an enthusiastic PhD student, who:

• Holds a Master degree in Neurosciences, Biomedical Sciences;
• Has proven interest in the neuroscientific field, with affinity for neurological diseases or neuroinflammatory processes;
• Is Art 9 qualified;
• Is fluent in English;
• Is highly motivated;
• Can work independently and in teams and has excellent communication skills.

You will first identify a robust animal-based model, study molecular and neuropathological changes, select quantitative markers and compare findings from the model with VWM patient data. Subsequently, the student will test FDA/EMA-approved drugs for inhibiting acute decline. Furthermore, you will:

• Familiarize yourself with VWM and underlying disease mechanisms;
• Familiarize yourself with the new models for acute neurological decline;
• Characterize new models using phenotypic scoring, immunostainings and molecular tests;
• Characterize drug treatment interventions;
• Perform essential PK/PD tests for translating the findings to human studies.