Progeria

Researchers are investigating new diagnostic and prognostic markers for cardiomyopathy (CMP) to better predict how the disease progresses, especially toward heart failure or the need for heart transplantation. The study focuses on microRNAs and spatial transcriptomics, promising techniques that may reveal important disease mechanisms. Patients with various types of CMP, including hypertrophic, dilated, arrhythmogenic, and forms related to amyloidosis and Fabry disease, are being evaluated to improve diagnosis and management. This observational study has both retrospective and prospective parts. Retrospective data from patients treated since 1990 will be collected from medical records, while prospective patients are enrolled from outpatient or inpatient settings at several medical centers. Patients undergo standard clinical tests such as ECG, echocardiograms, cardiac magnetic resonance (CMR), biopsies, and genetic testing. Additional molecular analyses on blood plasma and cardiac tissue will be done for some prospective patients. Tissue samples collected during routine biopsies or surgeries will be processed for advanced RNA analyses. Participants will provide informed consent and be evaluated according to clinical needs without a set minimum follow-up time. Data collected include demographics, medical and family history, symptoms, treatments, and genetic information. Researchers will use this information to identify new biomarkers related to CMP diagnosis and prognosis. The main outcome focuses on risk stratification over a follow-up of two years after a 30-month enrollment period, with data analysis lasting six months. Molecular studies of gene expression and microRNAs will also be analyzed during this time.

Researchers are studying striated muscle laminopathies, a group of genetic muscle diseases caused by mutations in the LMNA gene that affect skeletal and heart muscles. These conditions vary widely in symptoms, severity, and age of onset. The study aims to identify genetic factors, called modifier genes, that influence how severe the disease is in different patients, especially those with known LMNA mutations showing a range of clinical presentations. The study collects biological samples, including skin and muscle biopsies, from patients with LMNA mutations who do not have contraindications for these procedures. Skin biopsies involve removing a small piece of skin from areas like the forearm under local anesthesia to grow fibroblast cultures. Muscle biopsies are done under local anesthesia by taking a small muscle tissue sample, typically from the shoulder area, for laboratory analysis. These samples will be used for advanced molecular studies using multi-OMICs techniques to understand gene expression and chromatin structure. Participants will provide samples that are processed and sent to a biological resource center for detailed analysis. The study will measure various outcomes related to muscle and heart disease severity, as well as genetic and molecular factors over five years. Consent and social security affiliation requirements apply, and the study excludes pregnant or breastfeeding women and adults under legal protection. The overall study duration and follow-up involve evaluating changes in muscle and heart conditions alongside genetic findings.

This research focuses on laminopathies and emerinopathies, which are rare genetic disorders caused by mutations in the LMNA and EMD genes. These conditions often affect skeletal and cardiac muscles, with heart disease being a major cause of death. Since the 1990s, significant progress has been made in understanding their clinical and genetic variations, but precise links between gene mutations and disease symptoms remain unclear. Currently, there are no specific treatments to stop or slow disease progression beyond symptom management. The study is an observational registry called OPALE, designed to collect detailed information on patients in France with confirmed pathogenic LMNA or EMD gene mutations. It gathers genetic, neurological, heart, endocrine, and lung assessment data using a web-based platform. The registry aims to improve knowledge of disease progression, complication rates, and factors that influence prognosis. Participants will undergo yearly comprehensive clinical evaluations for up to 10 years to monitor their condition according to the study protocol. The researchers will track changes over time to better understand how the disease develops. This long-term observation helps provide insight into the natural history of laminopathies and emerinopathies and supports future research and care improvements.

Researchers are evaluating the safety of a vitamin-like substance called quercetin in people with a rare condition known as Dyskeratosis congenita (DC) or telomere biology disorders (TBD). This pilot study is open-label and single-arm, involving about 12 patients with DC or TBD. The study aims to understand how quercetin affects these patients over a 24-week period. Participants will receive quercetin orally twice daily, with doses adjusted based on their weight. The maximum total daily dose is 4000 mg, given in divided doses. For patients weighing 70 kg or more, the starting dose is set at the maximum level. The quercetin is supplied as a powder to be mixed with food like yogurt for home administration. During the study, participants will be monitored for any treatment-related side effects and for reasons that might cause them to stop taking quercetin. Assessments will include safety evaluations over the 24 weeks of treatment. The study is led by Children's Hospital Medical Center, Cincinnati, and aims to carefully track how participants respond to quercetin throughout the trial period.