Neuro-metabolic, structural and functional hallmarks of Lysosomal Storage Diseases

NeuroLSD project (No. 794986)
Neuro-metabolic, structural and functional hallmarks of Lysosomal Storage Diseases

WHO CAN PARTICIPATE? Patients with Mucopolysaccharidosis, Fabry disease, Gaucher type I and healthy individuals older than 8 years of age.

WHY? Sensitive and reliable metabolic and microstructural brain markers are desperately needed in Lysosomal Storage Disorders (LSD) to measure ongoing brain deficits, which are not sufficiently corrected by intravenous Enzyme Replacement Therapy (ERT) due to limited permeability of blood-brain barrier. Such markers are emergently needed for clinical trials to monitor the effects of novel cures that overcome the blood-brain barrier.

HOW? The recent advancement in Magnetic Resonance (MR) Imaging and Spectroscopy techniques, achieved at the Medical University Vienna, enables to monitor metabolism of the tissue in exceptional details. The combination of methods allows to quantify levels of microstructural, functional and metabolic brain damage and to distinguish areas of oxidative stress, inflammation, cellular brain damage and abnormal microstructure in the brain with accuracy that could not be achieved before.

How can YOU help?
Your participation in the project may critically improve lives of LSD patients and boost search of optimal brain-directed therapies in LSD!!!

ACADEMIC ABSTRACT of the project

Continuing development of novel brain treatments, which bypass blood-brain barrier, further emerges the need to establish prognostic magnetic resonance (MR) markers to track progressive brain alteration in lysosomal storage diseases (LSD). Excessive intracellular accumulation of lysosomal substances triggers multi-organ malfunctioning and significant damage to the central nervous system. While LSD are associated with various levels of cognitive deficits, and distinct extents of morphological brain abnormalities (e.g., atrophy, leukodystrophy or enlarged perivascular spaces) ranging from non-existing in GD type 1 to severe in MPS type 2, microstructural and metabolic processes have not been comprehensively described in brains of LSD patients in vivo yet.

We will utilize cutting-edge accelerated proton MR spectroscopic imaging methodology that was developed at the Medical University of Vienna in combination with advanced diffusion MRI, high-resolution T1-/T2-weighted ratio, and pseudo-continuous arterial spin labeling technique. Our protocol will reliably quantify levels of all relevant brain metabolites, while sensitively describe microstructural and functional deficits to determine the relevance of MR measures in psychological deficits in LSD. Reproducible MR methods are needed to assess the effects of novel treatments that overcome blood-brain barrier such as intrathecal enzyme administration, chaperones, and gene therapies in clinical LSD trials. Increased understanding of brain LSD pathology will critically boost the search of optimal therapies in age-related neurodegenerative diseases that share some common features with LSD such as Alzheimer’s or Parkinson’s disease.