Rare diseases collectively affect millions of people in the United States and hundreds of millions of patients worldwide. However, each of the estimated 7,000 to 10,000 of these diseases has a relatively small patient population, so scientists struggle to attract sufficient funding for therapeutic research and development, even when the hoped-for therapeutics could be lifesaving. Fortunately, several women pioneers currently champion this cause.
Researcher Behnaz Akbari personally lives with several of these diseases. She possesses a deep commitment to advancing the rare disease community and has authored prior AWIS articles on this topic. In May, a student-led organization that she founded—the Purdue University student chapter of NORD—received a $1,155 award from Purdue’s Graduate Student Government. Akbari’s unique perspective as both a patient and a scientist fuels her dedication to designing impactful projects aimed at improving the lives of those affected by rare conditions.
Karin Hehenberger, MD, PhD, is Chief Medical Officer of Patient Care America and President of Lyfebulb, an innovation accelerator she founded to focus on patient-centered approaches to chronic diseases, including rare ones. As a type 1 diabetic and organ transplant recipient, she has unique insights into the isolation and other challenges that rare disease patients face. She passionately aims to leverage emerging technologies such as AI, gene editing, and quantum computing to advance rare disease research.
Sharon Terry, a pioneering advocate in rare disease research, began her journey after her children received diagnoses for a rare genetic condition. As CEO of Genetic Alliance, she works to advance rare disease research through community-driven approaches.
Carrie Wolinetz, whose daughter was born with Smith-Lemli-Opitz syndrome—a disease that prevents the body from making enough cholesterol to grow properly— works as a science policy professional. Wolinetz, a former AWIS board member, demonstrates a deeply personal commitment to biomedical advocacy, particularly in the field of rare disease research, as she advocates for families like her own.
Nora Yang, CEO of Merlin Therapeutics, transitioned to a focus on rare disease research when she helped pioneer the Therapeutics for Rare and Neglected Diseases (TRND) Program at the National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS). The scientific precision of rare disease research (some with well-defined genetic causes) and the opportunity to significantly help patients with limited treatment options drew her to this field.
These dedicated professionals, with backgrounds in federal, private, and nonprofit sectors, recently painted a picture of the rare disease research landscape for us and highlighted a breadth of perspectives. Although their different backgrounds and roles lead to different areas of emphasis, they share common ground on the challenges and opportunities of this vital field.
Federal Funding
Funding sources for rare disease research fall into three main sectors: federal, commercial, and nonprofit. Until recently, most funding has come from the federal government, due to the limited commercial viability of rare disease therapeutics. The NIH has not only funded NCATS but also the Rare Diseases Clinical Research Network. The Food and Drug Administration (FDA) has also supported rare disease research. Funding also comes through rare disease research foundations, which get funds primarily from individual donations, grants from other foundations, and philanthropic contributions. Commercial enterprises sometimes provide limited funding to foundations for specific research activities, but they tend to focus on diseases with larger patient populations and may charge high prices for rare disease treatments (up to $1 million to $2 million per treatment).
The federal government has historically incentivized rare disease therapeutic R&D, although at least one national program—the FDA’s Rare Pediatric Disease Priority Review Voucher, which provided incentives for developing drugs for rare pediatric diseases—recently expired.
“For the short term, if I could make one change, it would be for the government to allocate more funding. A lot of these rare disease assets are stuck in development, and they require just a small amount of funding to cross that ‘valley of death,’” Yang said, referring to challenges encountered during the transition from laboratory experiments to clinical trials. “With a little bit of help, they could become commercially attractive, but this funding is really hard to come by, so the government should step up and invest.”
Yang calls for the government to renew its commitment to innovative policies. “The reason the rare disease field actually took off in the late 1990s and 2000s is because the FDA [created] policies like an orphan drug designation and provided both regulatory and market incentives. For example, the FDA provided accelerated approval and seven years of market exclusivity, as well as a pediatric rare disease voucher, a huge financial incentive that helped a lot of the small startup companies focusing on rare diseases attract funding and form strategic alliances with large pharma companies,” she explains.
Commercial Incentives
The FDA defines a rare disease as one that affects fewer than 200,000 people in the United States. This definition has its genesis in the Orphan Drug Act of 1983, a law that incentivized the development and production of drugs—orphan drugs—to treat rare diseases or conditions. The Orphan Drug Act incentives for rare disease drug development include tax credits for clinical testing, FDA user fee waivers, the Orphan Products Grants Program, and options for market exclusivity.
Additional regulatory changes could help address the problem of small patient populations. Wolinetz says, “Really working collectively is what got things like the Orphan Drug Act over the line, really banding together with this idea that there is a set of commonalities even through drastically different diseases.” She points out that as research has advanced, the collective population of rare disease patients has gotten even larger: “The more we understand cancers, the more we understand neurological diseases at really the cellular and molecular levels, it becomes clearer and clearer that in some ways, every cancer is a rare disease and could be treated on a very individual level in a personalized medical modality.” She identifies NORD as a model collaborative platform for rare disease advocacy to spread information, expand awareness, and overcome financial hurdles.
Rare disease legislation and market incentives have been effective at driving therapeutic development. In recent years, the FDA has seen an upward trend in the percentage of new drugs approved as treatments for rare diseases. According to the FDA’s latest New Drug Therapy Approvals Annual Report, published in 2024, 26 of the 50 (52%) Center for Drug Evaluation and Research novel drugs that won approval were rare disease therapeutics. “So [for the] long term,” Yang says, “if I could make one change today, it would be to continue to provide these types of policies that will help attract investment and perhaps even change policies to extend intellectual property protection for longer.”
In an AWIS Magazine article published earlier this year, “Unlocking Hope: The Significance of Orphan Drugs in Precision Medicine,” Akbari details the benefits of the orphan drug development landscape, including economic advantages. She writes, “Observers expect the global market for rare disease diagnostics to grow from $21.6 billion in 2024 to $34.7 billion by 2029, at a compound annual growth rate (CAGR) of 9.9%; the diagnostics market for rare cancers to expand from $11.2 billion to $18.2 billion at a CAGR of 10.2%; and the market for metabolic and endocrine disorders to grow from $1.5 billion to $2.4 billion, also at a CAGR of 9.9%.”
Asked to identify factors that make projects attractive for investment, Hehenberger adds, “For an investor who is not really interested in the details of the intricate science, there has to be a vision that you set up as your project, how this eventually will actually make a difference in the marketplace.” Just how much difference does a rare disease project need to make? Large pharmaceutical companies typically require potential markets that exceed $1 billion in sales.
In her 2024 article, Akbari details the important work of NORD, one critical collaborative platform for rare disease advocacy. NORD groups enable effective and efficient progress toward overcoming rare disease research challenges by supporting coordinated action.
Grassroots Funding
All the women we spoke with underscored the vital role of patients and patient advocacy groups. Both advocacy groups and foundations push for patient-centered, collaborative research by establishing research consortia that require data sharing; by filling critical funding gaps through creative campaigns and grassroots efforts; and by advocating for policy changes.
How can early-career investigators compete effectively for rare disease funding? They need to get involved with the patients and advocacy groups directly and ensure that these groups remain part of the process. Advocacy groups provide patients for the trials. They sometimes offer some direct funding, and many times, they also have the best understanding of patients’ needs, a key factor in making a compelling economic case down the line and in suggesting best directions for the research.
Hehenberger notes that “working closely with advocacy organizations and even helping to set up advocacy organizations” can also promote success for the pharmaceutical companies that conduct rare disease therapy research and development. She explains, “The most successful companies that have worked in rare disease therapeutic development have been those who partner with [trusted] advocacy organizations, because that’s how you can build patient registries, that’s how you can get that reach, because you might even know every single patient who has the disease, and therefore you can do clinical trials as well as get that advocacy in those areas where you need it.”
Wolinetz agrees and says, “When patients, when families, are able to share their personal experiences with some of these obstacles that are part of the system, they can have a really powerful impact. When advocates come forward with specific ideas and solutions, that is really, really helpful to policymakers, to help them put things together that could be moved forward in a real way.”
Terry highlights the critical role of patient consent, ownership, and active participation in rare disease research: “In the rare disease realm, people always say yes,” she explains. “They’ll have the mailman take their data if they think that the mailman could do something. They would post it in the Boston Globe, if they thought that somebody would see it and be able to do something.”
She shares a success story related to EspeRare’s work on treatments for X-linked hypohidrotic ectodermal dysplasia (XLHED), a rare genetic disorder that disrupts the ability to sweat: “We’ve repurposed a drug that we provide prenatally. Baby boys with this genetic condition, who receive the drug prenatally, are born sweating, and we have one now who is six or seven years old and a total of 10 little boys who are playing and running and biking.”
She notes, however, that results for many other diseases typically take much longer to assess: “Like my kids’ disease: If it takes all the way until you’re 40 for you to have an eye bleed, it’s hard to say what’s slowing the disease down or not, and so measures of impact prove difficult.”
She goes on to say that such cases require very long-term longitudinal studies: “A trusted entity, like a government, is going to be the only stable thing that will be around. The next best entities are the advocacy organizations. Because while labs close and companies go out of business and people hoard data, the advocacy organizations often are going to be a home for the population for a very long time.” She also mentions a key collaborative focus of the Genetic Alliance, an organization dedicated to bringing people and communities together to transform health. Because advocacy organizations tend to exist in “disease silos,” the Genetic Alliance has created “registries for all, a biobank for all, an Institutional Review Board for all, so that everybody can have one central, trusted space, since we’re not for profit and our values are really consistent with those of data sharing and of benefits for all.”
Looking to the Future
In general, research happens most effectively and efficiently at a global level, when academic institutions around the world collaborate with one another and when researchers build international clinical trials to get a broad, representative mix of patients, a pool that allows for a comprehensive assessment of safety and efficacy.
Terry strongly advocates for global collaboration due to disease rarity and infrastructure limitations, and she expresses enthusiasm about potential beneficial growth in international collaboration: “I am an eternal optimist, after 30 years of working in this field and hoping that, yes, even when scorched earth comes, we can get creative about figuring out other ways to do things, and we can forge new collaborations, and so on. So, I’m hoping that we’ll see more international collaboration.”
Wolinetz hopes for innovative trial designs that remove the challenge of requiring rare disease patients to travel to an academic medical center. She asks, “Are there remote participation possibilities? Can researchers partner with local medical providers to take measurements or give therapeutic interventions that are part of the trial? There hasn’t been the motivation to do that sort of innovation and clinical trials and clinical research, but that is the sort of thing that would really help the rare disease community.”
She also notes that the FDA is “not really set up right now” to approve platform technologies that doctors could apply to treat multiple rare diseases. It may take new legislation from Congress to give FDA these authorities. However, the FDA’s Center for Biologics Evaluation and Research shows some interest in platform approaches, particularly in those that involve gene editing technologies like CRISPR, where the delivery method remains consistent and the research team changes only the sequence according to the particular rare disease they target.
All these pioneering women share optimism about how new technologies can revolutionize rare disease research and treatment. Recent innovations—gene therapy, cell therapy, some targeted therapies—have worked especially well for rare diseases.
Yang notes that these newer technologies show promise in lowering research and development expenses, “making rare disease treatments more economically viable.” She highlights that “any technology that can replace or help reduce the sizes of expensive clinical trials and … that can move away from animal testing, which costs so much and isn’t predictive for clinical efficacy, would be valuable. Anything AI- or organs-on-chips-related that can reduce development costs, and technologies that can reduce manufacturing costs, particularly for things like the Adeno-Associated Virus [a vector for delivering new genetic material into cells], which currently can cost hundreds of thousands of dollars to produce, that you have to price a therapy at a million-dollar price point, [would help us with our funding challenges].”
Hehenberger agrees: “Being able to analyze large sets of data in a faster manner and to be intelligent about it is going to drive the field forward. I also think the advancements within gene editing are really important, because certain rare diseases do have those very genetic setups that are addressed through gene editing.”
Despite the funding challenges, rare disease researchers have myriad ways to get involved in the field and so much work to do. They can all play a role in advocating for policies that sustain funding for rare disease initiatives and incentives; in recognizing the invaluable contributions of patient advocacy groups and in supporting their integration into the research process; in exploring and leveraging innovative technologies that can streamline research and reduce costs; in identifying and clearly articulating the potential impact and market viability of these projects; and in considering strategic alliances for long-term investments, guided by robust science and a commitment to patient well-being.
During our conversations with these forward-thinking and pioneering women, we identified key recommendations to bolster research funding and therapeutic development:
- support government funding to bridge the “valley of death” in translational research (get therapeutic treatments into clinical trials;
- maintain and expand policy for commercial incentives;
- prioritize patient engagement and advocacy;
- foster strong collaboration and data sharing;
- and invest in technologies that can reduce research and manufacturing costs (e.g., in vitro models, organs-on-chips, AI-driven analysis).
Finally, patients and families must continue their advocacy, to share their stories, to build communities, and to demand greater attention and resources for rare disease research. Their voices are the driving force behind progress that ultimately leads to tangible breakthroughs and life-changing therapies.
Georgina To’a Salazar, PhD, works to create innovative solutions in science communication, research, and policy. With a BS in chemical engineering from Stanford University and a PhD in biomedical engineering from the University of California, Irvine, Dr. Salazar has fulfilled her dream of exploring the world, having taken research positions in Singapore and Japan before returning to the United States to focus on science communication. She currently works as a freelance scientific writer through her small business, Redwood Scientific Communications, LLC.
This article was originally published in AWIS Magazine. Join AWIS to access the full issue of AWIS Magazine and more member benefits.