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Chasing her own cure
With support from industry experts embedded at Stanford, Héloïse Hoffmann, ’26, is developing a therapy to treat her rare genetic disorder and others like it.
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Photo: Andrew Brodhead
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When Héloïse Hoffmann, ’26, was 10 years old, her muscles began to ache. Certain activities would leave her shoulders contorted for weeks, and debilitating pain would hit her seemingly out of the blue. For three years, doctors dismissed her concerns as growing pains or teenage fabrications. Finally, she got a diagnosis at thirteen: facioscapulohumeral muscular dystrophy (FSHD), a rare genetic disorder that causes muscles to weaken over time. She was told that no treatments existed. “I felt like my world as I knew it was over,” she recalls.
Hoffmann spent years in the fog of grief. Then, at 15, she watched a webinar from a patient advocacy group urging those with FSHD to get involved in the community, through fundraising and advocacy work. Without thinking twice, she launched herself in. It was only later, as she dove deeper, that she discovered her calling: applying science to FSHD. “I’ve always thought science is pretty cool,” she says. “What if I can use science to make this diagnosis more livable and advance our understanding of this disease?”
As an undergraduate at Stanford, Hoffmann has gotten farther in her mission than she ever imagined: She is developing a gene therapy designed to shut down the abnormal genetic activity that harms muscle cells in people with FSHD. With support from Stanford’s one-of-a-kind Nucleus at Sarafan ChEM-H—which provides access to state-of-the-art equipment, industry expertise, and other resources—Hoffmann is on her way to turning a promising idea into a real-world treatment.
“I’m literally chasing my own cure, and I feel so lucky for that chance,” she says.
Hoffmann started studying FSHD in high school, publishing a study that linked the condition to reduced sleep quality and working with a Yale School of Medicine lab to bioinformatically analyze the disorder’s genetic variations.
The summer after her freshman year at Stanford, while interning at a biotech firm, Hoffmann began reading scientific papers about the molecular root of FSHD in her free time. “I thought, ‘How can we stop this disease from literally eating away at my muscles day by day?”
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Hoffmann reviews a slide with bioengineering professor Stanley Qi and graduate student Goldie Roth. “Having mentors willing to get down to your level and say, ‘I believe in you’—that makes all the difference,” she says. Photo: Andrew Brodhead
FSHD is caused by genetic mutations that lead mature muscle cells to produce DUX4, a protein typically active only in embryos. In muscle cells, DUX4 triggers a cascade of harmful effects, inducing the death of muscle cells. As she read, Hoffmann realized that approaches currently under development to stop this mechanism had limitations. She had an idea: If we could introduce a re-engineered, benign form of DUX4 into cells, could it block the toxic version of the protein from activating the muscle-killing cascade ?
“Since my diagnosis, I have been told, ‘DUX4 is the culprit,’” she says. “I thought it would be exciting to play a dirty trick on DUX4 and say, ‘Gotcha.’”
Hoffmann got a chance to test her idea the following winter, when she joined a group of Stanford students participating in iGEM, a global synthetic biology competition. Her team won a gold medal after demonstrating, in experiments in cells in a dish, that their proposed therapy could block DUX4 from switching on genes that damage muscles.
For undergrads at most institutions, the research would’ve stopped there. “I might’ve thought, ‘Cool, that was an awesome project and it might potentially translate to a treatment option for patients with FSHD—but we don’t have funding or lab space to continue, so time to find another lab to join,” she says. That would mean pausing work on FSHD, since no one at Stanford was studying it.
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I’m literally chasing my own cure, and I feel so lucky for that chance.”Héloïse Hoffmann ’26
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Laura Gwilliams. Photo: Jess Alvarenga
Instead, Hoffmann and some teammates from her iGEM team were accepted into the Sarafan ChEM-H Undergraduate Entrepreneurship Program, which helps Stanford students develop biotech projects with support from faculty, industry professionals, and entrepreneurs. The program is part of the Nucleus, a network of labs that provides researchers across Stanford with the cutting-edge equipment and industry expertise they need to make discoveries that can lead to new medicines. As winners of the program, Hoffmann and her team were awarded $50,000 to develop their project.
Mark Smith, a former pharmaceutical researcher who now leads the Undergraduate Entrepreneurship Program at Sarafan ChEM-H, says the setup is atypical. Industry veterans embedded at Sarafan ChEM-H run their own labs rather than advising from the sidelines. "Our job is to help people translate their research into medicine," he says.
Hoffmann says Smith encouraged her to think ambitiously about how the research could move from the lab to the clinic and connected her with Stanford’s Innovative Medicines Accelerator, which helped her team synthesize gene delivery vectors ahead of testing their approach in vivo.
“It’s quite rare for undergrads to get this level of independence, and I am so grateful for what it means to the FSHD community,” Hoffmann says. “I’m convinced that this project could not have happened anywhere other than the Nucleus at Stanford.”
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Hoffmann and her teammates are developing a gene therapy designed to treat people with facioscapulohumeral muscular dystrophy (FSHD). She is one of those people.
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With support from Stanford bioengineering professor Stanley Qi, a renowned expert in epigenetics, Hoffmann and her team, including Alice Finkelstein, ‘27, and Goldie Roth, a graduate student in the Qi Lab, have expanded on her original idea by engineering additional proteins that could suppress harmful gene activity. Their experiments in muscle cells derived from patients with FSHD show that the approach effectively blocks DUX4 from activating toxic genes. This fall, they plan to begin testing the therapy in mice. If experiments are successful, they hope to progress to toxicity studies in larger animals, and later clinical trials.
Having graduated with a bioengineering degree last spring, Hoffmann will spend at least a year working on the project full-time as a researcher at Stanford. Eventually, she plans to pursue an MD/PhD and a career at the intersection of medicine, research, and advocacy for children with neuromuscular diseases.
If her therapy continues to prove effective, she aims to help bring it to patients, whether by launching a startup or partnering with an established company. “I’m hopeful this could become a game-changer for the world of FSHD and diseases driven by toxic transcription factors in general,” she says. “Even though I have FSHD, it does not have me.”
Mark Smith is director of Medicinal Chemistry at Sarafan ChEM-H N and codirector of the Small Molecule Portfolio in Stanford's Innovative Medicines Accelerator (IMA).
Stanley Qi is associate professor of bioengineering in the Schools of Engineering and Medicine. He is an institute scholar at Sarafan ChEM-H, a Chan Zuckerberg Biohub Investigator, and a member of Stanford Bio-X, the Stanford Cardiovascular Institute, the Maternal & Child Health Research Institute, the Stanford Cancer Institute, and the Wu Tsai Neurosciences Institute.
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Hoffmann and Goldie Roth, a graduate student in the Qi Lab, select sample slides. The team plans to test the therapy in mice and, if experiments are successful, progress to toxicity studies in larger animals, and eventual clinical trials. Photo: Andrew Brodhead
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