Multi-Center Validation of Biomarkers for Motor Neuron Disease

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DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (03) Biomarker Discovery and Validation, and specific Challenge Topic 03-NS-102: Standardization and validation of neurologic biomarkers. While many studies have identified putative protein based biomarkers for amyotrophic lateral sclerosis (ALS), all have used a limited number of total test subjects. Therefore large validation studies are required to confirm these potential biomarkers for ALS. Such validated biomarkers can then be advanced towards the clinic within diagnostic tests and assays to monitor drug efficacy in clinical trials. Since ALS is an orphan disease, multi-center clinical research studies are required to obtain the necessary number of patient and control samples in order to properly validate biomarkers for ALS. We are uniquely positioned to rapidly advance multi-center biomarker validation studies for ALS. We have established standard operating procedures for the collection of blood plasma and cerebrospinal fluid (CSF) samples. During the past year we have created a consortium of 20 medical centers and ALS clinics with IRB approval to utilize these standardized sample collection procedures. This consortium of clinics and clinical investigators includes many of the leaders within the ALS community. We hypothesize that select protein and antibody based biomarkers will be validated in a large, prospective study using CSF and blood samples from multiple clinics throughout the country. To test this hypothesis, we propose three specific aims that address a key challenge to initiate and rapidly advance a multi-center biomarker validation study for ALS. The first specific aim will collect biofluid samples using standard operating procedures at 20 ALS clinics throughout the country. The second aim is to perform a targeted ELISA and mass spectrometry based multiple reaction monitoring (MRM) assays to validate specific protein biomarkers for ALS. The final aim will use these same biofluid samples to validate the presence of specific antibodies to spinal cord proteins in ALS patients. This study will validate specific protein and antibody based biomarkers for ALS that will assist in the development of in vitro diagnostic assays for ALS. Given the experience of our collaborative team, we are confident in our ability to complete the proposed studies within the 2-year time frame of the Challenge Award. PUBLIC HEALTH RELEVANCE: The overall goal of the proposed study is to validate specific biomarkers for amyotrophic lateral sclerosis (ALS). ALS is a fatal motor neuron degenerative disease that can strike adults of any age, yet we know little about its causes and cannot rapidly diagnose ALS. Our validated protein and antibody based biomarkers for ALS will create quick diagnostic tests for ALS.