Preclinical/Co-Clinical Section

Baylor College Of Medicine, Houston TX

Investigators

Linked publications & trials

Abstract

3. ABSTRACT - Preclinical/Co-Clinical Section (PCS) Despite the successes of exome and whole genome sequencing in clinical practice, up to 50-70% of patients with suspected genetic disease remain undiagnosed likely because their disease-causing gene has yet to be discovered or because the clinical significance of variants identified in genomic studies remains unclear. In clinical care, the number of variants of uncertain significance often surpasses pathogenic and likely pathogenic variants when testing is performed. Consequently, there is a significant unmet need for new resources to resolve genes of uncertain significance and variants of uncertain significance in the clinical setting. Even when genetic testing is diagnostic, 90-95% of rare genetic disorders have no approved therapies. This translates to therapies available for only 5-10% of the nearly 25-30 million Americans living with a rare disorder. With rapid advancements in nucleic acid-based therapeutics, such as gene therapy, gene editing, mRNA therapy, and antisense oligonucleotide therapy, models for rapidly testing therapies are necessary so that these potential new treatment strategies can be translated to the clinic. Collaborations between clinician scientists and model organism researchers are necessary for facilitating this revolution in genomic medicine. Model organisms, such as the fruit fly and laboratory mouse, are important tools for aiding in the interpretation of variants of uncertain significance and for testing new therapies for rare disorders. Within the BCM Center for Precision Medicine Models (CPMM), a team of physician-scientists and model organism researchers work together to generate model organisms that impact patient care. The clinical experience of the CPMM Preclinical/Co-Clinical Section is necessary to guide variant selection and to inform the model organism decision-making process so that the most translatable models are developed. Whether the models are generated for new disease gene discovery, phenotypic expansion, or testing of interventions, this synergy between clinicians and scientists leads to the development of models with the highest impact on patient care. The impact of the Preclinical/Co-Clinical Section of the BCM CPMM extends beyond the variants accepted for modeling. The Section works closely with the Disease Modeling Unit and Bioinformatics Section to provide alternative recommendations for determining pathogenicity of variants that are ultimately not modeled within CPMM. The success of the Preclinical/Co-Clinical section is due to strong collaborative efforts between clinicians, genome scientists, bioinformaticians, and model organism scientists that are afforded by the integration of basic, translational, clinical, and diagnostic activities within the BCM Department of Molecular and Human Genetics. Our Preclinical/Co-Clinical section will continue to leverage this existing infrastructure and expertise and extend its use to the wider medical genetics and rare disease community through the following aims: 1) Coordinate and review variant submissions, 2) Refine the clinical questions requiring precision modeling, and 3) Translate clinical significance of precision models.