Authors :
Presenting Author: Zohreh Talebizadeh, PhD – Global Genes
Jade Gosar, MS – Global Genes
Vanessa Vogel-Farley, BS – Global Genes
Charlene Son Rigby, BA, MBA – Global Genes
Rationale:
Seizures frequently occur in many rare diseases, complicating both their diagnosis and management. Epilepsy, defined by recurring seizures, is a chronic neurological disorder caused by abnormal neuronal activity. Genetic mutations often influence the onset and progression of epilepsy, leading to diverse presentations and associated comorbidities. Understanding the full spectrum of seizure occurrence across different rare conditions is essential due to these complexities.
Methods:
As the research arm of the non-profit rare disease organization Global Genes, RARE-X has developed a platform that empowers patients and patient advocacy groups (PAGs) to actively contribute robust data to support therapeutic research. Unlike traditional approaches that organize data by individual diseases, the RARE-X platform collects patient-reported data based on shared and unique symptoms. Partnering with over 100 PAGs, RARE-X currently represents more than 70 rare disorders and has enrolled around 6,000 participants. Approximately 70% of the conditions on RARE-X involve neurological symptoms, and 50-60% are classified as neurodevelopmental disorders. By using a hypothesis-agnostic approach, RARE-X captures data on any symptoms, regardless of their known associations with specific conditions. This methodology enables comprehensive data collection and cross-disease comparisons, helping to identify patterns that might remain undetected in individual rare conditions.
Results:
The goal of this proof of concept study was to conduct a cross-disease analysis of seizures in rare diseases using RARE-X data. We analyzed patient-reported data from 10 rare conditions, categorizing them into two cohorts based on seizure frequency: uncommon (1-33%) and very common (50-85%). The study included 246 rare patients with seizures and 299 without. For the two conditions with the largest sample sizes (STXBP1 and CACNA1A), we examined the relationship between seizures and other symptoms within each disease. For the remaining eight conditions, seizure occurrence was analyzed independently of specific diagnoses to gain a broader understanding of seizure patterns.Conclusions:
Our findings highlight how RARE-X’s symptom-based data collection facilitates meaningful cross-disease comparisons. Such comparisons are critical in rare diseases, where limited sample sizes can obscure clinically significant patterns. Leveraging patient-reported data provides valuable insights into the frequency, co-occurrence, and impact of seizures, guiding more effective research and treatment strategies. This innovative approach not only deepens our understanding of rare diseases but also supports the development of targeted therapies, ultimately improving outcomes for patients with complex epileptic syndromes.
Funding: Biopharma grants and sponsored research agreements