An ENRRICH Spotlight on Rett Syndrome – Part 2: Dr. Galen Wright

Continuing from our previous spotlight on Rett Syndrome in conjunction with the Manitoba Rett Syndrome Association, we hear from Dr. Galen Wright. Dr. Wright specializes in researching how genomics – or someone’s entire DNA template – influences their brain development, health, and occurrences of diseases and disorders.

Let’s start with a brief overview of the research you do and how you became affiliated with the Manitoba Rett Syndrome Association

Thanks for asking. I started my research group at the University of Manitoba in 2020 with the goal of using human genetics and genomics to better understand neurological disorders, especially rare conditions affecting the brain. A major focus of our work is understanding why people with the same genetic diagnosis can have very different symptoms or disease courses. For example, some individuals may develop symptoms earlier, or experience more severe features, even when the primary genetic cause is the same. Studying the genetic factors that influence these differences is known as genetic modifier research, and it can help point us toward new treatment strategies.

Before starting our Rett syndrome work, I had been studying genetic modifiers in Huntington disease, an adult-onset neurological disorder. Around the time I started my lab, a study suggested that some of the same genetic pathways involved in Huntington disease may also be relevant to Rett syndrome. That cross-disorder connection was really interesting to us and led us to begin a research program focused on Rett syndrome.

In particular, these genetic modifier findings pointed toward DNA repair, which is the process cells use to repair damage that occurs in DNA. DNA repair is important in all cells, but it may be especially important in the brain. Since then, our lab has become increasingly involved in Rett syndrome research.

Through ENRRICH and other opportunities, we connected with members of the Manitoba Rett Syndrome Association, including Trish Guimond, who serves as president of the association. It is very meaningful to work closely with affected individuals and families. Those connections help ensure that the questions we ask in the lab are relevant to the Rett syndrome community.

What approaches do you use in your research for Rett syndrome, and how are they well-suited to study neurodevelopmental disorders?

Our lab is a human genetics and genomics research group, so we are especially interested in studying biology in human systems. Animal models have been extremely important for understanding brain development and neurodevelopmental disorders, but they do not always capture aspects of biology that are unique to humans.

This is particularly relevant for Rett syndrome, a rare neurodevelopmental disorder that predominantly affects girls. Rett syndrome is usually caused by changes in a gene called MECP2, which is located on the X chromosome. Because of the way many animal models have been developed, and the way symptoms appear in those models, much of the earlier research has relied heavily on male mice. Our lab is interested in complementing that work by using human cell-based models.

To do this, we use human stem cell models. These stem cells can be made from different starting materials, such as skin or blood cells, and then reprogrammed into a flexible stem cell state. From there, we can guide them to become different types of brain cells.

We also use gene-editing tools, including CRISPR, to study the effects of specific genes in these human models. CRISPR is a laboratory technique that allows researchers to make precise changes to DNA, which helps us test what specific genes do. In particular, we are interested in genes that may modify Rett syndrome features. By changing these genes in stem cell models, we can ask how they influence brain cell function in the context of disease.

To understand what is happening in these cells, we use newer genomic technologies. One example is single-cell sequencing, which lets us measure which genes are active in individual cells, across thousands of cells at once. This helps us understand how different cell types respond in Rett syndrome models. We also use long-read RNA sequencing. RNA is a temporary copy of the genetic information that cells use to make proteins and carry out their functions. Long-read RNA sequencing provides a more detailed view of how genes are processed and assembled into different RNA messages.

Although these technologies can sound complex, the goal is straightforward: we want to understand how genetic modifiers affect brain cell function in Rett syndrome. By doing this in human models, we hope to identify biological pathways that could eventually be targeted for new treatments.

What are human brain organoids? In what way are your organoids similar to the human brain, and how do they survive for long periods of time?

Human brain organoids are a newer technology that we can make from human stem cells. They are small, three-dimensional models that capture some features of early human brain development.

In the lab, we start with stem cells and group them together into small clusters. We then expose them to specific factors that help guide them toward becoming brain-like tissue. These factors are designed to mimic some of the signals that occur during early brain development. The organoids are then kept in a carefully controlled cell culture environment, where they receive the nutrients and support they need to grow and survive.

One of the remarkable things about brain organoids is that they can be maintained for long periods of time. Some research groups have shown that organoids can survive for more than a year, and in some cases even longer. In our lab, we have grown them for more than six months.

Over time, the organoids begin to develop different types of brain cells. Many people are familiar with neurons, but the brain also contains important support cells called glia, which help neurons function properly and contribute to overall brain health. Organoids can also contain early-stage brain cells, such as progenitor cells, which are cells that can give rise to more specialized brain cell types.

It is important to be clear that brain organoids are not miniature human brains. They are very small, roughly the size of a pinhead, and they do not have the full structure, complexity, or function of a human brain. However, they provide a useful window into some of the early developmental processes that happen in human brain cells. This makes them valuable for studying how Rett syndrome and potential genetic modifiers affect human brain development and cell function.

How can ENRRICH work with clinicians, families, and advocacy organizations to ensure that research findings translate into concrete improvements in clinical care, support services, treatment innovations and quality of life for individuals with Rett syndrome?

I think continued interaction between researchers, clinicians, advocacy organizations, individuals with Rett syndrome, and their families is essential. Research should be guided by the needs and priorities of the people most affected. That means making sure we are not only asking scientifically interesting questions, but also questions that matter to families and have the potential to improve care, support, treatment, and quality of life. These interactions are also very valuable for researchers. They help us understand the real-world importance of the work and keep the focus on outcomes that are meaningful beyond the lab.

ENRRICH is already doing important work in this area. For example, including patient and family partners in catalyst grants helps ensure that community perspectives are considered early, including during question development and research study design. Networking events, open houses, and similar opportunities also help build relationships between researchers, clinicians, families, and advocacy groups. 

The key is to continue creating and expanding these opportunities. The more we bring these groups together, the better positioned we are to move research findings toward practical improvements for individuals with Rett syndrome and their families.

What can ENRRICH do to raise public and policymaker awareness about Rett syndrome - not only as a rare genetic disorder, but as a chronic life-long condition requiring systemic support?

ENRRICH can help by continuing to share clear, accessible information about Rett syndrome as both a rare neurodevelopmental disorder and a chronic, life-long condition. Blogs, public events, and other knowledge translation activities are important ways to explain why ongoing research, clinical care, therapies, family support, and community services are needed.

It is also important to engage policymakers directly. Activities such as meetings with elected officials or participation in Parliament Hill Days can help communicate the importance of rare disease and neuroscience research.

Finally, the rare disease community is strongest when it works together. While individual conditions may be rare, rare diseases collectively affect about one in 12 Canadians. A shared voice can help advocate for sustained investment in research, care, and long-term support.

To hear more about Dr. Wright’s work with the Manitoba Rett Syndrome Association, please take a moment to view this video.

About the author

Dr. Galen Wright is an Associate Professor and Canada Research Chair in Neurogenomics in the Department of Pharmacology and Therapeutics at the University of Manitoba. He is also a Principal Investigator in the Neuroscience Research Program at the Kleysen Institute for Advanced Medicine. Dr. Wright’s research interests lie in precision medicine, neurology, and DNA repair in the brain. He completed his Ph.D. in Genetics at Stellenbosch University and received additional training in computational biology at the South African National Bioinformatics Institute. Dr. Wright moved to Canada in 2014 and completed a postdoctoral fellowship at the University of British Columbia (UBC). His work at UBC led to the identification of highly predictive genetic biomarkers for various adverse drug reactions, including drug-induced neurotoxicities in pediatric individuals. His precision medicine research includes the investigation of genetic modifiers in neurological disorders, including the neurodevelopmental disorder Rett syndrome.

Published June 1, 2026