Amyotrophic lateral sclerosis (ALS) is an adult onset, rapidly fatal, neurodegenerative disease of unknown etiology. The relatively low prevalence (6-8 cases per 100,000) and short survival time (3-5 years) of patients with ALS present impediments to establishing sizeable national cohorts needed for research. This is particularly true for efforts to develop biorepositories that collect central nervous system (CNS) tissue samples annotated with clinical information essential to biomedical ALS research. Although a number of mouse models have been developed to study ALS, these models are limited and the need for research quality human CNS tissue for genomic and proteomic research in ALS is critical. Studies have indicated a higher prevalence of ALS among veteran groups than among civilians. Because of this, the Department of Veterans Affairs (VA) started the VA Biorepository Brain Bank (VABBB) to support ALS research. The VABBB is presently the only national prospective cohort study and CNS tissue bank that is enrolling and conducting ongoing follow-up on veteran enrollees with ALS. The VABBB is a multi-site collaboration among VA Boston Healthcare System (VABHS), the Southern Arizona Core Tissue Laboratory (SACTL) at the Southern Arizona VA Healthcare System (SAVAHCS), and the VISN-1 Neuropathology Laboratory at the Edith Nourse Rogers Memorial Veterans Hospital in Bedford, MA. The VABBB utilizes the strengths across the Boston/Bedford and Tucson sites in enrollment, tissue banking operations, neuropathological diagnosis, medical informatics and data management. The VABBB cohort is notable for its size, the amount and quality of CNS tissue and clinical data available, and especially for the relatively long duration and slow disease progression in the cohort. Tissue and clinical data from the VABBB are available for distribution to qualified researchers. Recent studies have noted the importance of better classifying patients according to the relative salience of the cognitive/behavioral symptoms in ALS in order to improve our understanding of ALS pathophysiology. Accordingly, we seek to enhance our characterization of the VABBB cohort by prospectively screening for cognitive and behavioral impairment. Over the next four years the specific aims are: 1) To continue, and enhance, the VABBB as the only national ALS prospective cohort study and CNS tissue bank supporting ALS research in the U.S.;and 2) To characterize cognitive and behavioral dysfunction in our cohort to support research on the pathophysiology and clinical management of ALS.
For Specific Aim 1, the VABBB will continue to follow the present cohort of 127 veterans, enroll 140 new eligible veteran tissue donors, and continuously improve our overall methods. This will be accomplished through an outreach program across VAs nationwide, collaboration with other institutions, and improvement in our clinical assessment and CNS-tissue banking methods. The VABBB will also enhance its already robust national CNS tissue recovery network. This will involve 1) thorough neuropathological analysis of all brains and spinal cords with rigorous semi-quantitative documentation of the histopathological, immunohistochemical, and anatomical findings;2) collaborations with investigators to assess tissue for genetic mutations and polymorphisms;3) generation of a larger and more diverse collection of CNS tissue from Veteran controls;and 4) development of a national outreach program to further promote the use of VABBB tissue and data by ALS researchers.
For Specific Aim 2, a cognitive/behavioral telephone assessment will be added to improve cohort characterization and add value to future CNS tissue collection. These improvements will facilitate clinicopathological studies of ALS by correlating these cognitive/behavioral assessments with histopathological, immunohistochemical, and genetic data. The availability of high quality fixed and frozen CNS tissue and data from this well characterized cohort is an important resource to facilitate research into genetic and environmental risk factors and clinical pathological relationships in ALS.

Public Health Relevance

Amyotrophic lateral sclerosis (ALS) is an incurable fatal neurologic disease leading to progressive paralysis and, in many cases, cognitive decline. There is no effective treatment for ALS and it's ultimate cause remains unknown. Because studies suggest that veterans are at increased risk for ALS, VA established ALS as a 100% service connected disability. VA has made a major commitment to support research on ALS and funded the creation of the VA Biorepository Brain Bank (VABBB) as a national resource to support ALS research. Enrolled veterans with ALS across the country receive semi-annual telephone calls to collect health information. Upon a veteran's death, the VABBB arranges for the collection of brain and spinal cord tissue for processing, storage, and distribution to qualified ALS investigators. The availability of high quality tissue and clinical data from veterans enrolled in the VABBB is an essential resource to support research on the causes and effects of ALS and the development of effective treatments for those affected by this devastating disease.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
1I01BX002466-01
Application #
8661513
Study Section
Special Emphasis Panel (SPLH)
Project Start
2014-01-01
Project End
2017-12-31
Budget Start
2014-01-01
Budget End
2015-12-31
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
VA Boston Health Care System
Department
Type
DUNS #
034432265
City
Boston
State
MA
Country
United States
Zip Code
02130