Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease resulting from the loss of upper and lower motor neurons, typically fatal within 5 years of symptom onset. Our studies during the initial funding period have discovered protein biomarkers in ALS and candidate diagnostic biomarkers for ALS. However ALS progresses much more rapidly in some patients (death within 1 year from diagnosis) while others progress much more slowly (greater than 10 years from diagnosis to death). It is unclear why patients progress at quite differing rates, and few studies have explored disease progression within individual patients over time. We propose in this next funding period to generate a novel resource of longitudinal blood and CSF samples collected from ALS patients, neurologic disease controls, and healthy controls. We have extensive experience in collecting longitudinal samples from patients and controls and already have preliminary data indicating specific protein levels change during ALS disease progression. We will use these longitudinal samples to explore proteomic and extracellular RNAs (exRNA) to discover biomarkers for ALS disease progression. We will use both targeted and unbiased proteomic technologies, as well as novel exRNA methodologies in both blood and CSF. We hypothesize that specific biomarker signatures can be identified that correlate to clinical parameters of disease progression (fast vs. slow), therefore providing insight into molecular mechanisms that regulate disease progression. Our proposed studies will provide novel insight into proteomic changes during disease progression and characterize exRNAs in blood and CSF to discover novel exRNA biomarkers of disease progression. Finally, we will combine these complex proteomic and genomic datasets to discover biomarker panels for ALS disease progression.
This project will create a biorepository of blood and CSF samples from patients with amyotrophic lateral sclerosis (ALS) and control subjects. These samples will be used to identify new markers of disease progression that can be used to monitor drug effects in clinical trials and to stratify patients as fast or slow progressors. Our findings ill lead to new insights into how the disease progresses within individual patients and potentially new targets for drug therapy.
|Vu, Lucas T; Bowser, Robert (2016) Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis. Neurotherapeutics :|
|Liu, Xiaochen; Lu, Deyi; Bowser, Robert et al. (2016) Expression of Carbonic Anhydrase I in Motor Neurons and Alterations in ALS. Int J Mol Sci 17:|
|Li, Yang; Collins, Mahlon; An, Jiyan et al. (2016) Immunoprecipitation and mass spectrometry defines an extensive RBM45 protein-protein interaction network. Brain Res 1647:79-93|
|Li, Yang; Collins, Mahlon; Geiser, Rachel et al. (2015) RBM45 homo-oligomerization mediates association with ALS-linked proteins and stress granules. Sci Rep 5:14262|
|Bakkar, Nadine; Boehringer, Ashley; Bowser, Robert (2015) Use of biomarkers in ALS drug development and clinical trials. Brain Res 1607:94-107|
|Collins, Mahlon A; An, Jiyan; Peller, Danielle et al. (2015) Total protein is an effective loading control for cerebrospinal fluid western blots. J Neurosci Methods 251:72-82|
|Collins, Mahlon A; An, Jiyan; Hood, Brian L et al. (2015) Label-Free LC-MS/MS Proteomic Analysis of Cerebrospinal Fluid Identifies Protein/Pathway Alterations and Candidate Biomarkers for Amyotrophic Lateral Sclerosis. J Proteome Res 14:4486-501|
|Smith, Richard; Myers, Kathleen; Ravits, John et al. (2015) Amyotrophic lateral sclerosis: Is the spinal fluid pathway involved in seeding and spread? Med Hypotheses 85:576-83|
|Bakkar, Nadine; Kousari, Arianna; Kovalik, Tina et al. (2015) RBM45 Modulates the Antioxidant Response in Amyotrophic Lateral Sclerosis through Interactions with KEAP1. Mol Cell Biol 35:2385-99|
|Coyne, Alyssa N; Siddegowda, Bhavani Bagevalu; Estes, Patricia S et al. (2014) Futsch/MAP1B mRNA is a translational target of TDP-43 and is neuroprotective in a Drosophila model of amyotrophic lateral sclerosis. J Neurosci 34:15962-74|
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