Each month, we share summaries of recent Rare Diseases Clinical Research Network (RDCRN) grant-funded publications. Catch up on the latest RDCRN research below.
Jump to:
- Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN)
- Spastic Paraplegia Centers of Excellence Research Network (SP-CERN)
- Urea Cycle Disorders Consortium (UCDC)
Listen to these summaries on the Rare Research Report podcast.
Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN)
Developing a New Patient-Centered Approach to Clinical Trial Readiness in Aicardi-Goutières Syndrome
Aicardi-Goutières syndrome (AGS) is a type 1 interferonopathy primarily associated with multisystemic involvement, including severe neurologic impairment. With advancements in therapeutics for disorders such as AGS, there is an urgent need to ensure that patient voices are included early in the design of clinical trials.
In this study, researchers developed a new patient-centered approach to clinical trial readiness and piloted the approach in AGS. First, the team worked with patients and caregivers to identify their health priorities for improvement. Following this, the team engaged a panel of disease experts to identify the priorities applicable in the context of AGS clinical trials (Concepts of Interest). Next, through consensus building among a panel of outcome experts, the team selected Clinical Outcome Assessments able to measure the identified Concepts of Interest. Finally, the team presented the Concepts of Interest and the aligned Clinical Outcome Assessments to patients and caregivers to establish the feasibility of completion of these assessments in clinical trials.
This process led to the identification of a panel of fit-for-purpose Concepts of Interest and Clinical Outcome Assessments pairs that can be used to identify endpoints for future AGS clinical trials and natural history studies. Authors note that this approach can be applied to other leukodystrophies and rare diseases.
Sevagamoorthy A, Gavazzi F, Tashnim Z, Hong P, Vaia Y, Lee-Kirsch MA, Eleftheriou D, Beerepoot S, Hully M, Berry Kravis EM, Ventola P, Raspa M, Wheeler A, DeMauro SB, Glanzman AM, Townsend E, Duong T, Cusack S, Harrington AT, Pierce S, Fitzgerald M, Fazzi E, Galli J, Orcesi S, Tonduti D, Wassmer E, Cordova D, Adang LA, Butts C, Vanderver A. A novel patient-Centered approach to clinical trial readiness in rare diseases: Application in Aicardi-Goutières Syndrome (AGS). Mol Genet Metab. 2026 Mar;147(3):109765. doi: 10.1016/j.ymgme.2026.109765. Epub 2026 Feb 8. PMID: 41671914.
Spastic Paraplegia Centers of Excellence Research Network (SP-CERN)
Characterizing Movement Disorders and Treatment Responses in Aicardi-Goutières Syndrome
Aicardi-Goutières syndrome (AGS) is a genetic autoinflammatory disorder primarily affecting the brain, skin, and immune system. Individuals with AGS can experience a wide range of neurological symptoms, even when they have the same gene mutation, causing many to be misdiagnosed as having cerebral palsy.
In this study, researchers characterized movement disorders and treatment responses in AGS. The team evaluated motor symptoms, neuroimaging, and interferon signatures in seven children with AGS treated with immunomodulatory therapies.
Results show that these therapies were associated with reduced systemic inflammation and stabilized disease. However, only some participants experienced improved motor function, suggesting that established central nervous system injury may limit recovery. Authors note that these findings highlight the need for early recognition and treatment before further injury may occur.
Gonzalez Saez-Diez E, Ferrer Socorro M, Yang K, Battaglia N, Zaman Z, Bennett M, Vanderver A, Lee PY, Henderson LA, Andzelm MM, Ebrahimi-Fakhari D. Movement Disorders in Aicardi-Goutières Syndrome and Response to Immunomodulation. Ann Clin Transl Neurol. 2026 Apr 25. doi: 10.1002/acn3.70407. Epub ahead of print. PMID: 42033272.
Urea Cycle Disorders Consortium (UCDC)
Investigating Self-Reported Health-Related Quality of Life in Adults with Urea Cycle Disorders
Urea cycle disorders (UCDs) are a group of inherited, metabolic disorders characterized by hyperammonemia (high blood ammonia levels).
People diagnosed with a UCD often require ongoing health surveillance, long-term treatments, and emergency management for hyperammonemic episodes. Although many studies have focused on health-related quality of life in children with UCDs, fewer have focused on adults.
In this study, researchers investigated self-reported health-related quality of life in adults with UCDs. The team assessed patient-reported outcome measures in 144 adults with UCD.
Results reveal that adults with UCDs report similar health-related quality of life as adults in the general population. Despite significant differences in measured cognitive ability, symptomatic and asymptomatic individuals reported similar behavioral health and daily functioning scores. Authors note that more studies are needed to better understand and measure health-related quality of life in people with UCDs.
Coughlin CR 2nd, Barber J, Murali CN; Members of the Urea Cycle Disorders Consortium (UCDC); Wilkening G. Self-Reported Health-Related Quality of Life (HRQoL) in Adults With Urea Cycle Disorders. J Inherit Metab Dis. 2026 May;49(3):e70183. doi: 10.1002/jimd.70183. PMID: 41954389; PMCID: PMC13064420.
The Rare Diseases Clinical Research Network (RDCRN) is funded by the National Institutes of Health (NIH) and led by the National Center for Advancing Translational Sciences (NCATS) through its Division of Rare Diseases Research Innovation (DRDRI). Now in its fifth five-year funding cycle, RDCRN is a partnership with funding and programmatic support provided by Institutes, Centers, and Offices across NIH, including the National Institute of Neurological Disorders and Stroke, the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Heart, Lung, and Blood Institute, the National Institute of Dental and Craniofacial Research, the National Institute of Mental Health, the Office of Dietary Supplements, the National Institute on Aging, the National Human Genome Research Institute, the National Institute on Deafness and Other Communication Disorders, and the Office of Research on Women’s Health.
