A Multi-Dimensional Model of cAre and transItion for Patients With cOmplex RAre Diseases

Summary

Over the past century, the progress in biomedical sciences gave outstanding contributions to the understanding of human conditions, and even curing some of them. Recent advances in high-throughput technologies have enabled the profiling of Rare Diseases (RDs) trough genomics, transcriptomics, proteomics, and metabolomics. Regardless of the improvements in the efficiency of data generation, the research community struggles when stepping into bedside and translational processes. The lack of integrated networks between specialists of referral hospitals, local healthcare services and researchers represents a major challenge impacting outcomes of patients with RDs and overall family well-being.

The "Agostino Gemelli" University Hospital (GUH) is a leader in the national and international scenario on the clinical management of individuals affected by RDs with more than10.000 patients followed per year, 19 Units certifying different RDs and 16 of them belonging to the European reference Network. Nevertheless, even though the Units by themselves have a well-organized level of competencies, the network of specialists inside and outside hospital, the transition models from pediatric to adult age and the connection between referral centers and territorial services need to be optimized.

The current project aims to build the foundation of a multidimensional model helping clinicians overcoming the gaps mentioned above. Starting from the strength of a comprehensive and diversified clinical experience of specialists from GUH (HUB) and Metabolic and Genetic Unit at the Giovanni XXIII Children's Hospital in Bari (Spoke) a standardization of diagnostic and therapeutic coding according to MONDO Disease Ontology coding, Human Phenotype Ontology (HPO), and Anatomical Therapeutic Chemical (ATC) coding, will be performed. IT services will develop an electronic Case Report Form (eCRF) to collect and match data and experienced physicians will perform a functional diagnosis using the InterRAI multidimensional tools. Multiomics profiling will be performed by using the Gemelli-Science and TEchnology Park (G-STEP) facility (HUB) and the Institute for Genetic and Biomedical Research, National Research Council (Spoke) will generate induced pluripotent stem cell lines and isogenic cell lines by genome-editing technologies from selected patients with RDs. A Multidisciplinary Board for Rare Diseases (MBRD) with members of all Units will assess criteria for patient enrollment, will provide integration of clinical and molecular data and based on results, it will plan a personalized medical care strategy. To ensure the cross-sectional application of the model proposed to the broadest number of RDs, the participating Units will select four specific populations (from pediatric to adult age) affected by RDs. Measurable outcomes will arise from analysis of the mean time between first contact with the specialist and establishment of the etiologic diagnosis as well as reduction in the number of hospital visits, missed visits and loss of follow-up. The above data from patients enrolled in the present study will be compared to those collected in the two years prior Sars-Cov-2 pandemic (2017-2019) by querying data from the Regional Registry for RDs. This study performed on four major selected groups of RDs represents a model potentially applying to larger groups of RDs

Conditions

• Rare Diseases
• Mitochondrial Diseases
• Muscular Dystrophies
• Dysmorphic Disorder, Body

Interventions

DIAGNOSTIC_TEST

Etiopathogenetic diagnosis

Coding phenotype using standardized nomenclature systems, skin biopsy, blood sampling, nasal brush, and oral cavity swabs

DIAGNOSTIC_TEST

Functional diagnosis

Standardized scales for functional assessment of the patient

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  lead OTHER

Principal Investigators

• Giuseppe Zampino · Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-10-29

Primary Completion

2026-01-28

Completion

2026-05-31

Countries

• Italy

Study Locations