JAX cares about rare

More than 400 million people around the world suffer from a rare disease. As the name suggests, rare diseases are just that -- rare. In the United States, a rare disease is defined as one that impacts fewer than 200,000 people. Because so few people suffer from these diseases, they’re often overlooked and treatments can be illusive. The Jackson Laboratory is changing that.

Through its Rare Disease Translational Center (RDTC), JAX is driving

genomic discoveries that bring hope to patients and families. The RDTC aims to empower the global biomedical community by developing tools and treatments for some of the more than 10,000 rare diseases that are known to exist.

In 2019, rare disease cost nearly $1 trillion in the United States, according to a study from the EveryLife Foundation for Rare Diseases; a staggering burden for families who have already had their lives turned upside down by a rare disease diagnosis. With few resources available, these families are often forced to lead their own search for answers, balancing caring for their loved ones and becoming de facto medical and scientific experts overnight.

For families navigating the complexities of rare diseases, hope often feels out of reach. That’s where the RDTC steps in – turning hope into action through cutting-edge research and personalized scientific support.

Collaborating with families and foundations, the center develops genetically-engineered mouse models that mimic patients’ rare disorders. These models are then used to test potential therapies. Having led 100+ programs over the years, created 70+ novel mouse models and worked with 40+ families, the RDTC holds an immense amount of knowledge. This work impacts not just families but the entire rare disease community, and has implications for more common diseases including Alzheimer’s disease and cancer.

At the forefront of this work are the RDTC study directors, scientists who dedicate their careers to finding solutions for families affected by rare diseases. Their work is a testament to why JAX cares about rare – because behind every rare disease is a family searching for answers.

Hear from some of our study directors below.

Jennifer SanMiguel earned her bachelor's degree in biology from Colby College. Seeking hands-on research experience before graduate school, she joined Dr. Lou Kunkel’s lab at Boston Children’s Hospital, where she studied neuromuscular disorders such as Duchenne Muscular Dystrophy. During this time, she developed expertise in molecular biology and genetics, becoming particularly fascinated by how single nucleotide changes in DNA can profoundly impact human health.

After three years, she pursued a Ph.D. in cell and molecular biology at the University of Pennsylvania, focusing on genetics and epigenetics. Her research examined a protein in a knockout mouse model that regulated genomic imprinting, deepening her interest in gene regulation. While she loved the project, she sought research with more direct applications to human health, leading her to a postdoctoral position in the Trowbridge lab at The Jackson Laboratory (JAX). There, she investigated how mutations in epigenetic regulator proteins contribute to pre-cancerous states and accelerate the progression of blood cancers.

Motivated to pursue even more translational research, SanMiguel transitioned into a study director role with the Rare Disease Translational Center (RDTC). This position perfectly aligns with her scientific expertise and passion for using animal models to advance treatments for genetic diseases, ultimately striving to improve patient outcomes.

What projects are you currently working on for the RDTC?

I work on various rare disorders, including neurodevelopmental, neurodegenerative and epilepsy syndromes. Some of the disorders I study are Infantile Neuroaxonal Dystrophy (INAD), HNRNPH2-related neurodevelopmental disorder, SLC6A1, DDX3X, and Friedreich’s Ataxia.

Is there a project that is particularly meaningful to you? What inspired you to pursue this project?

All my projects are meaningful for different reasons, especially because of the people affected and involved. However, our work with INADcure stands out. INAD is a very aggressive neurodegenerative disease. Meeting Leena Panwala, INADcure’s president and mother of Ariya, a young girl with INAD, along with her team, including Neil Hackett, moved me deeply. Their passion and the urgent need for therapies for these children inspired me.

INAD is caused by the lack of a functional protein. We are testing whether adding back the missing or non-functional gene through gene replacement therapy can improve the health and lifespan of a mouse model of the disease.

Can you share a moment or achievement from this project that stands out to you?

One of the most exciting moments during our preclinical trials was when we saw differences in the survival curves. Seeing that our gene-therapy-treated mice lived longer was incredibly encouraging and made us feel closer to bringing a tangible treatment to the clinic.

How does this project contribute to the impact of the RDTC?

This project showcases our ability at the RDTC to conduct large, well-controlled preclinical drug studies. These studies provide definitive data on whether a therapy is effective. The data can be used to submit a new investigational drug application to the FDA, allowing the therapy to move into clinical trials. We work quickly and precisely to get results for the foundation, helping them make informed decisions about continuing with clinical programs. This project has given the green light for INADcure to proceed.

How has this project influenced your approach to other research projects?

This project taught me patience, as it took longer than expected for differences between treatment groups to appear. Initially, it wasn’t clear if the therapy was working or if the mice had the right symptoms. Eventually, the differences became apparent. It also taught me the importance of rigor and commitment to high-quality data, which I apply to all my projects, regardless of their stage in the drug development pipeline.

What resources at JAX have been beneficial to your work and supported the success of this project?

The people I work with are the main reason for this project's success. We have an incredible team of technicians who carefully monitor the mice and record data. My project manager keeps everything on track and monitors incoming data in real time. My research assistant handles all post-study analyses to understand how the therapy works at a molecular level. We also collaborate closely with the clinical laboratory animal medicine, histology services and pathology services teams, whose care for the mice and samples has been instrumental in our success.