Development and validation of diagnostic biomarkers for neurodegenerative conditions based on MRI measures of pathognomonic brain regions

Amyotrophic Lateral Sclerosis (ALS) is a devastating, relentlessly progressive neurodegenerative condition with no effective disease-modifying therapies and no validated biomarkers. Three main themes exist in ALS biomarker research; (1) development of diagnostic indicators, (2) identification of accurate prognostic markers and (3) validation of reliable monitoring markers which enable the objective assessment of new drugs.



Currently, the diagnostic delay from symptom onset to definite diagnosis is about 13 months, which delays recruitment into pharmaceutical trials and initiation of neuroprotective therapy. Pharmaceutical trials in ALS currently solely rely on clinical measures and survival as their primary end-points as no objective and validated biomarkers exist. Distinguishing early-stage ALS from overlap syndromes, and other neurodegenerative conditions can be challenging, and accurate biomarkers may be particularly helpful.



Magnetic Resonance Imaging (MRI) allows for a widely available, non-invasive and relatively low-cost method of evaluating structural abnormities of the central nervous system (CNS). Novel quantitative MRI modalities such as Diffusion Tensor-Imaging (DTI), Magnetic Resonance Spectroscopy (MRS) and functional MRI (fMRI) allow accurate and structure-specific assessment of specific brain regions. Network and circuitry integrity can be objectively evaluated by novel diffusion techniques, whereas atrophy patterns can be mapped with density and cortical thickness analyses. Biochemical and metabolic imaging signatures can be monitored non-invasively with MR spectroscopy. Despite significant advances, these technologies have not been harnessed to their full potential in ALS.



We have previously described disease-, phenotype-, and genotype-specific imaging signatures in ALS and our preliminary diagnostic studies indicate that non-invasive MRI modalities can be developed into accurate diagnostic, prognostic and monitoring biomarkers. Validated biomarkers in neurodegeneration have implications for diagnositc applications, clinical management, pharmaceutical trials, and deciphering the progressive pathophysiological changes driving progressive neurodegenerative changes.

Award Date
04 July 2017
Award Value
€741,799
Principal Investigator
Dr Peter Bede
Host Institution
Trinity College Dublin
Scheme
Emerging Investigator Awards