Author: Keon Deng
January 13, 2026 at 11:00 AM
We discuss rare disease research and its unique challenges in our interview with Dr. Christina Lam to gain a physician-scientist's perspective. She is currently working at the University of Washington and Seattle Children’s Hospital, where she studies congenital disorders of glycosylation (CDGs) and related metabolic disorders. She’s the Principal Investigator for the Frontiers in Congenital Disorders of Glycosylation Consortium Natural History Project, part of the Rare Diseases Clinical Research Network. Rare diseases affect a smaller subset of the population than common diseases. As such, there are nuances in rare disease research arising from this smaller population, both in funding and in strategy. According to Dr. Lam’s experience, research on rare diseases often lacks a substantial body of scientific literature to build upon. A lack of information and limited patient populations require a greater emphasis on collaboration with patients with rare diseases and patient advocates.
Upon conducting her research on CDGs, Lam found that there were more established research foundations in European countries compared to the United States. She explains, 15 years ago, “there was a huge black hole in the United States…very few clinical experts and researchers focused on this group of genetic conditions.” This meant patients with CDG may have issues both in diagnosis and a lack of effective treatment for this disease. There were instances where there was a need for treatment, but “patients didn’t have someone to really…latch on to.” To navigate this, she relies on networking with people interested in rare diseases, focusing on the community, and repurposing treatments that may be applicable, but were tested in a different population outside of CDG.
Challenges conducting research isn’t just an issue specific to CDG; some rare disease research rely on international registries (systematic databases of health information compiled from different countries) due to limited sample sizes and few studies conducted in the United States.[1] There is an overall absence of reliable epidemiological estimates of the prevalence and incidence of rare diseases, which remain largely unavailable at both the national and global levels.[2] This problem is further exacerbated by the difficulty in diagnosing some rare diseases clinically. For example, CDG can variably affect multiple organs and bodily functions, and genetic testing is often necessary to confirm the diagnosis and type.[3] However, in recent years, many promising improvements in information sharing have emerged by building and expanding rare disease communities. Around the world, there have been growing partnerships and collaborations among patient advocacy groups, researchers, the biopharmaceutical and bioengineering industries, and governmental research and regulatory agencies focused on different rare diseases.[2] Research is progressing for many rare diseases, and there has been a rapid expansion in the discovery of new CDG types, with the number of newly identified phenotypes increasing annually.[4]
While international collaboration has certainly accelerated progress, there are still clinical challenges that Dr. Lam, who must balance being both a clinician and a scientist, keenly feels. On one hand, medical practitioners want to treat the problem as soon as possible, but new and promising treatments lack extensive clinical data. Furthermore, administering the treatment without pre-established clinical research protocols means that data that could otherwise be used for clinical research, such as the development and evaluation of the treatment, is no longer possible. Gathering clinical data requires significant time and effort. Dr. Lam notes, “it costs families a lot to be a part of our research studies…so I’m very mindful of the burdens…and very grateful that the families are willing to participate to try to answer…the scientific question [we’re] trying to ask.”
For Lam, advocacy groups have been an immense source of help. They fulfill roles that clinicians cannot, such as connecting families with similar diseases and facilitating discussions to build a stronger community for their rare disease. They can also provide explanations and give a voice on what’s important to patients on behalf of families or individuals who find it difficult to express these opinions in clinical settings. For example, something a doctor recommends may not work for the patient, but by giving patient organizations direct patient feedback, they can provide feedback on what’s important to patients. This external information from a different group can be highly beneficial for trial design. In addition, they can help promote the study and recruit patients, as well as provide a strong rationale for why the study is particularly important for the grant application.
Securing grant funding is also very difficult for rare disease research. Overall, there is decreased interest in investing in rare diseases due to a limited target demographic, resulting in smaller reimbursement for this new research by pharmaceutical companies.[5] One way around this limited interest may be the research’s potential applicability to other, more common diseases. One such example is the discovery of statins, initially developed to treat a rare condition affecting the LDL receptor but later found to be effective in the general population for reducing high cholesterol levels. Research into rare diseases can yield deeper insights into pathology that apply to more common diseases. Governmental programs like priority review by the FDA of drugs and biologics designed to treat rare pediatric diseases, and task forces like the International Rare Diseases Research Consortium (IRDiRC) seek ways to increase funding for rare disease research by engaging investors in both the public and private sectors, as well as foundations and advocacy groups.[6]
Research on rare diseases matters because it significantly impacts diagnosis and treatment. Rare diseases, especially those lacking sufficient research, often involve complex diagnostic journeys that may take 5 years or longer 7. It can also lead to constant, extensive testing by many specialists, who repeatedly refer patients to another specialist, who in turn refers them to yet another, repeating a process known as a “diagnostic loop”.[7] This process is further exacerbated by a lack of coordination or management between different healthcare professionals.[7] For CDG, diagnosis is difficult due to the varied symptoms present, such as delays in development, hypotonia, seizures, intellectual disability, and many more that may affect entire body systems in different combinations. Although the time to diagnosis has decreased in recent years to an average of 3.9 years, there are still frequent misdiagnoses, with rates of 44.9% for PMM2-CDG and 64.8% for non PMM2-CDG.[7]
Recognizing both the challenges and nuances that rare disease research presents, the role of collaboration for the rare disease community becomes increasingly clear. Research extends beyond simply gathering data and churning out outcomes. We observe interactions among companies, government institutions, researchers, and the rare disease population that have contributed to the discoveries in treatment and diagnosis. Sustaining these collaborative efforts and increasing funding for rare disease research will have a profound impact on simplifying diagnostic journeys and discovering more effective treatments that will transform the world for the many people living with rare conditions.
References
1. Mascalzoni D, Paradiso A, Hansson M. Rare disease research: Breaking the privacy barrier. Appl Transl Genom. Jun 1 2014;3(2):23–9. doi:10.1016/j.atg.2014.04.003
2. Groft SC, Posada de la Paz M. Rare Diseases: Joining Mainstream Research and Treatment Based on Reliable Epidemiological Data. In: Posada de la Paz M, Taruscio D, Groft SC, eds. Rare Diseases Epidemiology: Update and Overview. Springer International Publishing; 2017:3–21.
3. Ng BG, Freeze HH. Perspectives on Glycosylation and Its Congenital Disorders. Trends Genet. Jun 2018;34(6):466–476. doi:10.1016/j.tig.2018.03.002
4. Francisco R, Brasil S, Poejo J, et al. Congenital disorders of glycosylation (CDG): state of the art in 2022. Orphanet J Rare Dis. Oct 19 2023;18(1):329. doi:10.1186/s13023-023-02879-z
5. Vavassori S, Russell S, Scotti C, Benvenuti S. Unlocking the full potential of rare disease drug development: exploring the not-for-profit sector's contributions to drug development and access. Front Pharmacol. 2024;15:1441807. doi:10.3389/fphar.2024.1441807
6. Beaverson KL, Julkowska D, Letinturier MCV, et al. The IRDiRC Chrysalis Task Force: making rare disease research attractive to companies. Ther Adv Rare Dis. Jan–Dec 2023;4:26330040231188979. doi:10.1177/26330040231188979
7. Granjo P, Pascoal C, Gallego D, et al. Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community. Orphanet J Rare Dis. Nov 1 2024;19(1):407. doi:10.1186/s13023-024-03389-2
