Before there can be any therapies for disease, scientists need to understand what goes wrong in the first place. Are cells lost that could be replaced? Is there too much or too little of a particular molecule that needs regulation?  Stem cells can be used as mini models of a disease to find biological targets for new therapies.

One of the CIRM grantees who is doing this important stage of research is Julia Kaye, PhD, at the Gladstone Institutes. With her CIRM funding, Dr. Kaye is studying cells from people with Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig’s disease). She starts with patient cells called induced pluripotent stem cells (iPSCs), and then turns them into motor neurons, which are the type of cells damaged in people with ALS.  She then examines the neurons using a special microscope that allows her to see how the cells behave over time, and to better understand the disease.

Scientists use iPSC models for several purposes. For example, they can test drugs to see if they slow or reverse the disease, or they can learn more about how mutations in different genes alter the way the disease progresses. In Dr. Kaye’s work, she is using machine learning to compare neurons made from people with ALS to neurons from people without the disease to identify differences and test the effect of potential therapies.

In addition, approximately 10% of ALS cases are caused by mutations in specific genes, but the majority of cases are sporadic, with an unknown cause. While many research groups have studied the form of ALS caused by known mutations, it has been challenging to create models of the sporadic form. Dr. Kaye is working to develop such models using iPSCs from patients with sporadic ALS, with the goal of uncovering the varied underlying causes of ALS pathology. By doing so, Dr. Kaye hopes to provide insights that could lead to new therapies and benefit a broader range of patients.

Dr. Kaye recently answered some questions about her career and research, in particular her work with CIRM funding. You can read the entire story on the Gladstone Institutes’ website, in which she discusses the influence of her mother on her research, her love of surfing, and the future of her field of research.

Here, we’re excerpting what she has to say about using stem cells to model disease:

“A key focus of my work has been developing highly faithful models of neurodegenerative diseases using human cells. Ever since the invention of pluripotent stem cell technology, we have had the ability to study cells that come directly from patients with disease. The problem, however, has been that these cultures are naïve— they represent early stages of development and they often don’t effectively model the type of cells we’re really interested in. I think that has been a very confounding challenge for using iPSCs to model disease effectively. Even still, we’ve been able to capture robust disease-related cellular signatures, as well as uncover pathological cellular mechanisms not previously known. I’m very excited about what the future holds for this technology and how it may lead to drug discovery and also just basic understanding of disease.”

In previous work, Dr. Kaye was part of a large team of scientists that developed and studied iPSCs from people with ALS. She and others are studying those cells’ DNA, gene expression, and proteins to better understand the disease. This tour de force effort is called Answer ALS.  Dr. Kaye says, “I was thrilled to be a part of such an exciting and ambitious effort.  The collection of the cells was recently completed, but the efforts to study all of this data are just really beginning. These data and cell lines are available to scientific researchers, and will transform what we know and how we understand ALS in the years to come,” she said. 

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Written by guest contributor Amy Adams