Looking through a new lens: insights into patient participation in rare disease research

Orphanet Journal of Rare Diseases is proud to present this blog article by Meagan Collins, a runner-up entry in beacon for rare diseases and Medics4RareDiseases' "Student Voice" contest.

Approximately 7000 rare diseases have been identified. Over 300 million people are affected by rare diseases worldwide. One of the greatest challenges faced by rare disease families is the journey to diagnosis. The increasing availability of genome sequencing has helped to elucidate a diagnosis for many rare disease patients. The U.K. 100,000 Genomes Project was launched in 2013, and it utilized whole-genome sequencing, with the hopes of improving diagnostic and clinical outcomes for undiagnosed rare disease patients.

I had the privilege of speaking with JHW, a patient advocate, member of the board for the CureGRIN Foundation, Chair of the Participant Panel for the U.K. 100,000 Genomes Project at Genomics England, and a member of the NHS Digital Research Advisory Group. In 2017, JHW’s son was the first patient in the National Health Service to receive a genetic diagnosis of a variant in GRIN1 through the U.K. 100,0000 Genomes Project. In recent years, patients with rare diseases have helped to fast-track the development of treatments by participating in research. Patient participants and patient advocates are now taking a more active role in research strategy and coordination.

GRIN-related neurodevelopmental disorders and other GRI Disorders
CureGRIN Foundation was co-founded in 2019 by parent caregivers initially searching for a cure for GRIN-related neurodevelopmental disorders (GRIN1, GRIN2A, GRIN2B, and GRIN2D). GRIN-related neurodevelopmental disorders are extremely rare, with only about 426 individuals reported in the GRIN Portal, though the predicted incidence of the disorders is much higher.

In 2021, CureGRIN Foundation expanded their genes of interest to include all ionotropic glutamate receptor genes (collectively referred to as “GRI genes” and “GRI Disorders” by the organization) in hopes of bringing together more patients with similar clinical presentations and leveraging the research efforts for these disorders. Many patients with GRIN-related neurodevelopmental disorders and other GRI Disorders experience symptoms of developmental delay, intellectual disability, epilepsy/seizures, autism spectrum disorder, muscular hypotonia, movement disorders, cortical visual impairment, feeding difficulties, and other related symptoms.

As with most rare diseases, there are currently no U.S. Food and Drug Administration-approved treatments available for GRIN-related neurodevelopmental disorders or other GRI Disorders. Therefore, CureGRIN Foundation’s goal is to find treatments and potential cures for people around the world affected by single-gene disorders related to the GRIN genes encoding the N-methyl D-aspartate (NMDA) receptors, GRIA genes encoding the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, GRIK genes encoding the kainate receptors, and GRID genes encoding the delta receptors. JHW stressed that for this goal to be achieved, patients, clinicians, researchers, pharmaceutical/biotechnology companies, and patient advocates need to collaborate synergistically.

Leveraging patient participation in research
As a result of the rare nature of rare diseases, locating patients and patient samples can be challenging. CureGRIN Foundation has directed its efforts toward employing the Collaborative Network Approach first developed by Dr. David Fajgenbaum and his colleagues for advancing biomedical research for another rare disease called Castleman disease.

Traditionally, funding research projects involves fundraising by organizations, requesting proposals, experts reviewing the proposals, and awarding the funds to the top proposal. Moreover, biomedical research has previously focused more on health questions that were important to researchers and physicians, while seeking little feedback from patients and families. However, it has become evident that the questions and health outcomes that are important to the patients and their caregivers do not always align with those of researchers and healthcare professionals. Conversely, the Collaborative Network Approach involves building a community of key stakeholders (i.e., healthcare professionals, researchers, patients, and families), prioritizing a research agenda, identifying the best researchers, raising funds, obtaining samples and enrolling patients, executing the study, analyzing the data, identifying specific treatments, and sharing the outcomes of the study.

Every data point has a face”: informed consent, data collection, and data storage
There are several important considerations for patients participating in rare disease research including informed consent, proper data collection, and sufficient data storage and protection. As outlined by the International Rare Diseases Research Consortium and the Global Alliance for Genomics and Health, informed consent is especially important for the rare disease community to ensure that patient autonomy is maintained, the needs of the participants are met, privacy is maintained, and that data is used ethically.

The path forward: integrating research and patient care
For JHW and her son, driving research forward to have a meaningful impact on patient care and quality of life is of the utmost importance. As parents, caregivers, researchers, and healthcare professionals, we all have a role to play in advocating for and finding treatments and cures for patients affected by rare diseases, and there is power in our collective ability to unite around this common purpose.

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