A patient-derived iPSC platform of disease relevant cell models for biological studies

Project Overview

One of the greatest advancements in science over the past 10 years is the development of induced pluripotent stem cells (iPSCs). These cells make it possible to create essentially any cell type in the body using any other as a starting point. In ALS, iPSCs provide the opportunity to take skin or blood cells from someone living with the disease and turn them into motor neurons and other relevant cell types so that we may study human cells with the exact genetic makeup of the person donating them. In this Hudson project, the team will create iPSCs from 40 people living with ALS, including individuals with different hereditary genetic mutations, those with typical disease progression and those with atypical disease features. These iPSCs will then be made into motor neurons and astrocytes (the personal assistant cells to motor neurons that are also actively malfunctioning in ALS). Furthermore, using a special technology called CRISPR-Cas9, the team will specifically change the mutations in those from hereditary cases back to the correct form so that they may also be studied alongside those with the mutations. These are called isogenic controls and are a highly sought after resource in the global ALS research community. Using these newly developed motor neurons and astrocytes, the team will first determine if they develop any specific characteristics that can be correlated with the disease course and examine if they show differences as compared to others in the study. Furthermore, they will use these cells to develop novel tests for screening drug treatments that may be able to indicate an ability to slow down disease processes in human motor neurons. Finally, the team will also take advantage of this unique model of ALS to learn more about how the disease occurs. Using a technique called quantitative proteomics, they will examine all of the substances involved in the communication between human motor neurons and astrocytes in these lab cultures.

Partners and Donors

ALS Society of Canada