Meet Dr. Megan McCain: A Bright, Young Researcher Dedicated to Discovering New ALS Therapeutics

Innovation plays a key role in The ALS Association’s fight to develop treatments and a cure for ALS and to empower people living with ALS to live their lives to the fullest. During June and July, we are celebrating some of the key innovations helping us change the nature of the disease forever.

Today, we are happy to be joined by Dr. Megan McCain, an assistant professor of Biomedical Engineering and Stem Cell Biology and Regenerative Medicine at the University of Southern California (USC), an ALS researcher who recently received an investigator-initiated starter grant award from The ALS Association. These awards are designed to help bright researchers start their own labs to answer their own innovative questions addressing ALS disease.

Dr. McCain is dedicated to discovering new potential ALS therapeutics and better understanding ALS disease mechanisms using a unique and innovative tool called “Skeletal Muscle on a Chip.”

“Because I am new to the skeletal muscle field, it is difficult for my lab to receive major funding for this research,” she said. “Funding from The ALS Association is helping my lab collect preliminary data so that we can continue to develop and fine-tune our ’Skeletal Muscle on a Chip’ platforms, which we can then evolve into new systems for ALS drug discovery.”

Dr. Megan McCain
Dr. Megan McCain, Assistant Professor of Biomedical Engineering and Stem Cell Biology and Regenerative Medicine, University of Southern California (USC)

Dr. McCain recently told us more about her important work and allowed us to get to know the person behind the laboratory bench.

As an ALS researcher, what inspires you?

I am most inspired by the idea that our technologies could help develop personalized therapies for ALS. Diseases like ALS, which are relatively rare and can vary significantly from patient to patient, have been very challenging to effectively study using conventional approaches, such as mouse models.

Our engineered “Skeletal Muscle on a Chip” devices, combined with patient-derived cells, have unique potential to reveal new insights into mechanisms of the different forms of ALS. Our devices can also serve as platforms for discovering new drugs for a specific patient or category of patients, which can have a huge impact on many patients and their families.

I hope to someday see our platforms used to help develop personalized cures for patients suffering from ALS and other muscular diseases.

What is your academic background and current position?

I received my B.S. in biomedical engineering from Washington University in 2006 and my Ph.D. in engineering sciences from Harvard University in 2012. I then did a postdoc at the Wyss Institute for Biologically Inspired Engineering. In 2014, I started my current position as an assistant professor of Biomedical Engineering and Stem Cell Biology and Regenerative Medicine at USC.

Why did you choose to join the ALS field?

My interest in ALS started by talking with another faculty member at USC, Justin Ichida. In his lab, they generate motor neurons using cells derived from patients with ALS and use the motor neurons to understand how the disease progresses within the neurons.

However, a major function of these neurons is to form connections with skeletal muscle and activate their contraction, and his lab did not have a robust method for engineering skeletal muscle or measuring the amount of muscle contraction.

Our “Skeletal Muscle on a Chip” platform can address these needs, so we initiated a collaboration, which started my lab’s research in the ALS field.

What is the background of your research project?

My research lab is focused on engineering “Organ on Chip” platforms. “Organs on Chips” are devices that we microfabricate to closely mimic the natural environment that cells experience in our bodies. We then grow human cells (from people with ALS, if possible) in these devices, which form miniature tissues that we can reproducibly study in the lab.

For example, instead of growing heart cells randomly on a plastic dish, we grow them on soft hydrogels that we micromold with thin lanes. The micromolded lanes cause the heart cells to align (which is how they are organized in our body) and the soft hydrogel matches the mechanical properties of the native heart.

As a result, our engineered muscle tissues are more reproducible and stable in culture. Importantly, our “Skeletal Muscle on a Chip” devices allow us to engineer and measure the function of patient-specific human muscle tissues in response to disease-relevant perturbations, such as specific genetic mutations or drugs, which is very powerful for drug discovery and personalized medicine.

Engineered skeletal muscle
Skeletal Muscle on a Chip: Chick myoblasts were engineered into aligned skeletal muscle fibers by culturing on micromolded gelatin hydrogels. Red indicates sarcomeres, the contractile filaments in skeletal muscle. Blue indicates cell nuclei. (Image courtesy of Jeffrey Santoso and Megan McCain)

What has the support from The ALS Association meant to you and how will your award push your project forward?

As a trainee, my research was primarily related to the heart. When I started my own lab in 2014, I wanted to continue research on the heart, but also expand into new directions.

Because heart and skeletal muscle have many similarities in their structure and function, my lab started translating many of our “Heart on a Chip” devices to engineering new “Skeletal Muscle on a Chip” devices.

One application we are very excited about is using our “Skeletal Muscle on a Chip” devices for modeling diseases that need a personalized approach to drug development, due to the vast amount of genetic variability seen in patients, such as ALS. However, because I am new to the skeletal muscle field, it is difficult for my lab to receive major funding for this research.

Funding from The ALS Association is helping my lab collect preliminary data so we can continue to develop and fine-tune our “Skeletal Muscle on a Chip” platforms, which we can then evolve into new systems for ALS drug discovery.

Tell us about your exciting research project.

Skeletal muscle is responsible for all of our voluntary body movements and contracts when activated by motor neurons, which transmit signals from the brain. In ALS, the connections between motor neurons and skeletal muscle, known as neuromuscular junctions, degenerate.

To study ALS today, researchers commonly use animal models, such as mice, which have limited relevance to human forms of the disease and are expensive and have low-throughput. To overcome the limitations of animal models, the goal of my lab is to engineer human “Skeletal Muscle on a Chip” platforms to integrate with motor neurons derived from ALS patients.

First, we will optimize a platform that can both maintain engineered skeletal muscle in the lab for at least three weeks and enable us to measure the contractile strength of the muscle. Next, we will add human motor neurons derived from patients with ALS to the skeletal muscle tissues, which will be provided by our collaborator, Professor Justin Ichida.

We anticipate that the motor neurons will form neuromuscular junctions with the muscle, as they do in the body. To evaluate the health of these junctions, we will measure muscle contraction in response to neuron activation.

Ultimately, we and others can use this as a new platform to understand the progression of human ALS and screen drugs more effectively and efficiently compared to existing animal models. Importantly, because we can use cells from patients with ALS, our platform could also enable researchers to develop cures for ALS on a patient-by-patient basis.

What is the overall impact of your research on the ALS field and how can it lead to potential ALS treatments?

Our platforms will allow us and others to directly test if promising therapies can recover the function of engineered neuromuscular tissues with ALS-relevant mutations. This is important pre-clinical data that could help accelerate the development of cures for ALS.

Because we can acquire cells from patients, we can someday perform these experiments on a patient-by-patient basis and develop personalized treatment strategies. This personalized approach is critical for ALS, because many different types of genetic mutations have been observed in patients.

Thus, we can help identify the best treatment strategy for an ALS patient depending on [that person’s] mutation.

Help advance the fight against ALS and the work of ALS researchers like Dr. McCain, as well as provide care services and advocacy for people living with ALS and their families. Donate today.

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