Accession Number : AD1050346

Title :   Chemical Library Screening for Potential Therapeutics Using Novel Cell-Based Models of ALS

Descriptive Note : Technical Report,15 May 2016,14 May 2017

Corporate Author : Southern Illinois University Carbondale United States

Personal Author(s) : Gagnon, Keith T

Full Text :

Report Date : 01 Jun 2017

Pagination or Media Count : 17

Abstract : The leading cause of inherited amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a microsatellite repeat expansion in the C9ORF72 gene. This disorder is referred to as C9FTD/ALS. The disease mechanisms are still poorly understood. However, it is clear that the repeat expansion sequence is made into RNA that can aggregate in the nucleus of patient cells. The expansion RNA can also be translated into repetitive polypeptides in the cytoplasm of patient cells. These two processes are expected to play key roles in the initiation and progression of disease at the molecular and cellular level. Drugs that can block or reverse these processes would hold promise as therapeutics to treat C9FTD/ALS. The overall goal of this project is to develop new cell-based models of C9FTD/ALS that recapitulate these two disease processes. RNA foci and repetitive polypeptides will be visible through fluorescence microscopy. These cells will then be used for high throughput chemical library screening to identify and characterize molecules with therapeutic potential. For this Annual Progress Report, we report on progress for year 1 according to the proposed Statement of Work. The major task of Year 1 was to generate neural stem cells that inducibly express fluorescently-labeled foci and repetitive polypeptides. Toward this task we have successfully engineered inducible expression vectors for the C9FTD/ALS repeat expansion and created neural stem cells that express the tetracycline receptor protein. We are working to overcome unexpected pitfalls and combine these sub-tasks together to complete Milestone 1. We are currently preparing preliminary cell models to send to the Stanford HTBC for initial screening to meet milestones for year 2.

Descriptors :   ribonucleic acids , fluorescence , models , sclerosis , medical screening , dementia , genes , peptides , molecules , stem cells , proteins

Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE