A Community-Led Approach as a Guide to Overcome Challenges for Therapy Research in Congenital Disorders of Glycosylation

Abstract

Congenital Disorders of Glycosylation (CDG) are a large family of rare genetic diseases for which effective therapies are almost nonexistent. To better understand the reasons behind this, to analyze ongoing therapy research and development (R&D) for CDG, and to provide future guidance, a community-led mixed methods approach was organized during the 4th World Conference on CDG for Families and Professionals. In the quantitative phase, electronic surveys pointed to the prioritization of six therapeutic R&D tools, namely biobanks, registries, biomarkers, disease models, natural history studies, and clinical trials. Subsequently, in the qualitative phase, the challenges and solutions associated with these research tools were explored through community-driven think tanks. The multiple challenges and solutions identified administrative/regulatory, communication, financial, technical, and biological issues, which are directly related to three fundamental aspects of therapy R&D, namely data, sample, and patient management. An interdependence was traced between the prioritized tools, with diagnosis and therapies acting as bidirectional triggers that fuel these interrelationships. In conclusion, this study’s pioneering and adaptable community-led methodology identified several CDG therapy R&D gaps, many common to other rare diseases, without easy solutions. However, the strong proactive attitude towards research, based on inclusive and international partnerships and involving all members of the CDG community, sets the direction for better future therapy R&D.

Benefits and Risks of Sharing Genomic Data for Research: Comparing the Views of Rare Disease Patients, Informal Carers and Healthcare Professionals

“…For people suffering from a rare disease, benefiting from personalised treatments that take into consideration their individual genetic variability, environment exposures and lifestyle is a legitimate and expectable aspiration. Some patients spend a large part of their lives without a diagnosis, or are misdiagnosed, which impedes them from accessing appropriate care [ 7 , 31 , 32 , 33 ]. The hope lent by genomics research to predict disease and introduce molecular therapies tailored to each patients’ specific needs [ 34 ] may help to explain why patients in our study perceived the development of personalised treatments as one of its most prominent benefits.…”

Congenital disorders of glycosylation (CDG): state of the art in 2022

“…Nevertheless, in the last years, research has led to the discovery of novel biomarkers and disease models. Currently, there are four ongoing observational studies (NCT04201067, NCT02089789, NCT04198987, and NCT03404856), including two natural history studies (NCT03173300 and NCT01417533) and four therapeutic clinical trials (NCT04833322, NCT04679389, NCT03404869, and NCT03404856) [ 17 ]. The fact that most CDG involve the brain constitutes a significant barrier to treatment [ 18 ].…”