Turning rare disease research into a common goal

A bad deal and an amazing gift

As a baby, Annabel's AHC symptoms were frequent and severe, involving multiple ambulance trips to the children’s hospital. “Her neck would twist to the side, she would pant and flush, and her eyes would deviate uncontrollably – nystagmus is the medical term,” says Annabel’s mother Nina Frost. “She would be completely non-responsive.” In search of a cause, Annabel was checked for epilepsy and a brain tumor before AHC was finally diagnosed. “When you first hold your baby, you naturally have expectations for what your life will be like. But no one knows what cards you’ll be dealt,” says Nina, now president of the RARE Hope foundation.

We’re very fortunate with Annabel. She is the greatest gift we could have gotten. She’s such a sweet person. We joke that one of our disease’s phenotypes is that the kids are loving and truly care about others. It’s a very clear trait: Annabel loves her life and finds happiness in things we might miss. She has also given us a look into a world we never would have known existed.”

As we became part of this small AHC community, we’ve formed really close relationships with others living our lives. I’m also fortunate to work with a team of fellow patient parents who are smart and deeply committed to advancing therapies for rare diseases. There’s a true sense of family, and we see ourselves in a position to serve this family.

Building a constellation of hope around the patient

Through their first foundation, HOPE for Annabel, the Frosts established what Nina calls a “constellation of studies” – a comprehensive therapeutic research program. “We’ve built a network involving many institutions, universities and commercial labs, but at the core, we are the hub, uniting and representing the interests of the patients we serve,” says Nina. “We want to ensure that the research focuses on what they want and what matters most to them.”

Drawing on her management consulting background, Nina found her ability to quickly master new areas invaluable in this complex field. “Early on, it felt like learning an entirely new language,” she says. “Now I’m fluent and this fluency is critical to how I make strategic decisions, bring the right collaborators together and advance our program effectively.”

Surveying patient communities to understand their symptom burden is central to Nina’s approach. “We work with scientists to incorporate these patient insights into our studies, and to keep them centered around the patient – it is a very productive dynamic.”

Innovation attracts innovators

Nina and Simon's patient-first approach has driven significant scientific progress. In July 2025, they co-authored a groundbreaking paper published in Cell with gene editing pioneer Dr. David R. Liu at the Broad Institute of MIT and Harvard. The research, funded by a $2 million grant from the Chan Zuckerman Initiative, examined prime editing as a potential treatment for AHC. Dr. Cat Lutz of The Rare Disease Translational Center at The Jackson Laboratory, a leading expert in mouse modeling, co-led the study.

Their research program goes beyond gene editing. They collaborate with Tim Yu, a leader in developing antisense oligonucleotides (ASOs) – personalized treatments that can silence faulty genes before causing damage. The team is also focusing on biomarker discovery to monitor disease progression and developing more lab models to test potential treatments, from the microscopic C. elegans worm commonly used in neurological research to advanced organoids that replicate human organs.

“We found success by building relationships with top academics,” Nina explains. “When you collaborate with leaders in the field, it becomes easier to attract additional partners interested in advancing pioneering work and supporting new initiatives.”

But urgency fuels every breakthrough. “Even within our small AHC group, we hear every month or two about another death,” Nina says about their close-knit community. “Time is running out for these patients.”

Applying AI in drug repurposing

“Drug repurposing is one of the therapeutic approaches that we are prioritizing,” says Nina, highlighting how existing drugs can potentially treat conditions different from those they were originally designed for – saving years and hundreds of millions of dollars in R&D and regulatory approval.

A groundbreaking collaboration has recently been initiated with Elsevier. The AI-powered analysis examined nearly 2,000 drugs, utilizing curated knowledge graphs supported by datasets that include biological relationship data and statistical scoring to prioritize drug candidates based on their interaction with disease-related targets, especially sodium/potassium ATPase, which plays a key role in AHC pathology. The team also identified 22 proteins directly connected to AHC, along with other factors affecting ATPase expression.

These results are being cross-validated using two other approaches: a drug prediction algorithm from Unravel Bioscience via the rareSHIFT program, and the disease expertise of a multidisciplinary team of scientists within the AHC network. “Our goal is to create an intelligent library of drug candidates that can be tested in different laboratory models,” says Nina.

“We’re very excited about AI’s potential for rare disease research. I believe it will fundamentally transform how we analyze the datasets we’re collecting. We aim to be early adopters, but only where the signal is strong enough for decision-making. We’re validating AI predictions against multiple datasets and expert insights to reduce experimental risk.”

Scaling beyond a single disease

Over a year ago, the Frosts expanded their mission beyond AHC to address how to advance therapeutics across all rare diseases through their new foundation, RARE Hope. “I think we’ve always thought broadly about rare diseases. Our vision has grown from what we’ve seen and experienced over the years,” says Nina.

“Once you’re in the world of rare diseases, your mission naturally broadens. It’s not just about your own disease; it’s about all these other disorders, patients and groups. You keep discovering new rare diseases, and you wonder, how could it get any worse? There are patients suffering from truly unbearable symptoms.”

A cross-disease approach tackles a core issue: each rare condition usually exists as a separate entity, even though they may share disease mechanisms and common therapeutic platforms (such as gene editing and RNA-based treatments). By connecting these isolated areas, RARE Hope aims to create economies of scale – a specialty of Annabel’s father Simon – that make research more efficient and draw in more investment.

A hidden epidemic reveals a vast opportunity

Collectively, rare diseases are much more common than their name suggests. About 10,000 disorders affect hundreds of millions worldwide, with 30% of affected children dying before age five. Meanwhile, 80% of rare diseases have a genetic cause, which brings focus and hope. “Rare diseases provide unique insight into human biology,” says Nina. “Monogenic disorders reveal a source of dysfunction and the sequelae of that single gene mutation. By understanding the different consequences of each mutation, we're creating a map of human biology. In other words, each individual disorder offers clues to a much bigger picture that’s useful across both common and rare conditions. In many ways, our approach parallels Anna Greka’s inspiring work on nodal biology and ‘molecular sleuthing.’”

From passion to improved outcomes

The timeline is ambitious. “In two to three years, I would like to have two new clinical trials underway – an ASO trial and a prime editing trial – along with a highly predictive biomarker that could serve as a surrogate endpoint for these clinical trials. I would also like to have identified a repurposed drug that could help improve the quality of life for AHC patients and that could also assist patients with other disorders.”

The main challenge is funding. “Organizations aren't doing cross-disease research because funds are scarce and spreading them across diseases may feel riskier,” Nina acknowledges. However, she believes demonstrating value in cross-disease drug and biomarker discovery could attract pharmaceutical companies to the cause.

Recent advances in gene editing boost Nina’s optimism. “Gene editing isn’t science fiction anymore. Stories like Baby KJ – a baby successfully treated with gene editing – demonstrate how this major technological breakthrough can already significantly benefit patients. Technologies developed for rare diseases often pave the way for wider progress. Gene editing could revolutionize both rare and common disorders.”

An ever-expanding family

Finding the right work-life balance must be tricky with Nina’s job so closely connected to her family life. “We do fine, but work is a kind of compulsion. I don't really turn my brain off. I will think of something at one in the morning and start emailing,” she admits. “There’s also a lot of heartbreak that comes with it. But it’s wonderfully rewarding to make a difference in the world alongside others who are so committed and passionate.”

And this community is only expected to grow in the number of patients, partners and funders – all working toward making therapeutic breakthroughs more common for all diseases.