Development of therapies for rare genetic disorders of GPX4: roadmap and opportunities
| Autor: | Simon C. Johnson, Qitao Ran, Kristen Wigby, Dorian M. Cheff, Sanath Kumar Ramesh, Elias S.J. Arnér, Reena V. Kartha, Edward E. Schmidt, Brent R. Stockwell, Matthew D. Hall, Plavi Mittal, Alysson R. Muotri |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Future studies Sequencing data Pharmacology toxicology Sedaghatian-type spondylometaphyseal dysplasia Review Disease Glutathione peroxidase 4 Osteochondrodysplasias Rare genetic disorder Rare Diseases Therapy development Genetics medicine Humans 2.1 Biological and endogenous factors Ultra-rare disease Pharmacology (medical) Aetiology Intensive care medicine Genetics (clinical) Genetics & Heredity Other Medical and Health Sciences business.industry allergology General Medicine Human genetics Drug repositioning Roadmap Orphan Drug Good Health and Well Being Spondylometaphyseal dysplasia SSMD Medicine business GPX4 |
| Zdroj: | Orphanet Journal of Rare Diseases, Vol 16, Iss 1, Pp 1-15 (2021) Orphanet journal of rare diseases, vol 16, iss 1 Orphanet Journal of Rare Diseases |
| ISSN: | 1750-1172 |
| Popis: | Background Extremely rare progressive diseases like Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) can be neonatally lethal and therefore go undiagnosed or are difficult to treat. Recent sequencing efforts have linked this disease to mutations in GPX4, with consequences in the resulting enzyme, glutathione peroxidase 4. This offers potential diagnostic and therapeutic avenues for those suffering from this disease, though the steps toward these treatments is often convoluted, expensive, and time-consuming. Main body The CureGPX4 organization was developed to promote awareness of GPX4-related diseases like SSMD, as well as support research that could lead to essential therapeutics for patients. We provide an overview of the 21 published SSMD cases and have compiled additional sequencing data for four previously unpublished individuals to illustrate the genetic component of SSMD, and the role of sequencing data in diagnosis. We outline in detail the steps CureGPX4 has taken to reach milestones of team creation, disease understanding, drug repurposing, and design of future studies. Conclusion The primary aim of this review is to provide a roadmap for therapy development for rare, ultra-rare, and difficult to diagnose diseases, as well as increase awareness of the genetic component of SSMD. This work will offer a better understanding of GPx4-related diseases, and help guide researchers, clinicians, and patients interested in other rare diseases find a path towards treatments. |
| Databáze: | OpenAIRE |
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