National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77, Stockholm, Sweden.
Orphanet J Rare Dis. 2021 Oct 23;16(1):446. doi: 10.1186/s13023-021-02048-0.
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.
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We provide an overview of the 21 published SSMD cases and have compiled additional sequencing data for four previously unpublished individuals to illustrate the genetic component of SSMD, and the role of sequencing data in diagnosis.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.
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.
像 Sedaghatian 型脊椎干骺端发育不良（SSMD）这样极其罕见的进行性疾病在新生儿期可能致命，因此未被诊断或难以治疗。最近的测序工作将这种疾病与 GPX4 突变联系起来，导致相应的酶，即谷胱甘肽过氧化物酶 4 出现问题。这为患有这种疾病的人提供了潜在的诊断和治疗途径，尽管朝着这些治疗方法前进的步骤往往很复杂、昂贵且耗时。
CureGPX4 组织的成立旨在提高人们对 GPX4 相关疾病（如 SSMD）的认识，并为可能为患者带来重要治疗方法的研究提供支持。我们概述了 21 例已发表的 SSMD 病例，并为之前未发表的 4 例个体汇编了额外的测序数据，以说明 SSMD 的遗传成分，以及测序数据在诊断中的作用。我们详细介绍了 CureGPX4 为实现团队创建、疾病理解、药物再利用以及未来研究设计的里程碑所采取的步骤。
本综述的主要目的是为治疗罕见、超罕见和难以诊断的疾病制定治疗方案，并提高对 SSMD 遗传成分的认识。这项工作将更好地了解与 GPx4 相关的疾病，并帮助指导有兴趣治疗其他罕见疾病的研究人员、临床医生和患者找到治疗途径。
