SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Maze Therapeutics, a company translating genetic insights into new precision medicines, today announced the publication of research validating the protective role and mechanism of an APOL1 genetic variant– p.N264K— in chronic kidney disease (CDK) and end stage kidney disease (ESKD) among carriers with high-risk variants.

加利福尼亚州南旧金山-（商业线）-Maze Therapeutics，一家将遗传见解转化为新型精密药物的公司，今天宣布发表研究，验证APOL1遗传变异p.N264K的保护作用和机制-在具有高风险变异的携带者中的慢性肾病（CDK）和终末期肾病（ESKD）中。

The research was published online, in the Journal of the American Society of Nephrology (JASN) in collaboration with the Million Veteran Program and Vanderbilt University Medical Center..

这项研究是与百万退伍军人计划和范德比尔特大学医学中心合作在《美国肾脏病学会杂志》（JASN）上在线发表的。。

Apolipoprotein L1 (APOL1) is a protein encoded by the APOL1 gene in humans. Genetic variants of the gene (G1 and G2) are associated with increased risk for a spectrum of progressive kidney diseases in people of African ancestry. Maze researchers, along with their collaborators, previously identified and described the protective role and mechanism of a genetic variant in APOL1– p.N264K– in which presence of the variant was shown to reduce conductance of ions through the APOL1 pore thereby suppressing the toxicity of APOL1 in kidney cells and disease progression..

载脂蛋白L1（APOL1）是由APOL1基因编码的蛋白质。该基因的遗传变异（G1和G2）与非洲血统人群中一系列进行性肾脏疾病的风险增加相关。Maze研究人员和他们的合作者，先前确定并描述了APOL1-p中遗传变异的保护作用和机制。N264K-在这种变异的存在被证明可以降低离子通过APOL1孔的电导，从而抑制APOL1对肾细胞的毒性和疾病进展。。

“While the genetic link between APOL1 and kidney disease has been well-established, the mechanism by which it induces kidney injury had remained uncertain for nearly a decade,” said Harold Bernstein, M.D., Ph.D., president, research and development, and chief medical officer of Maze. “Through this research and earlier research conducted at Maze, we have established a better understanding of APOL1’s mechanism in kidney disease and how we may be able to intervene with a medical therapy.

医学博士，博士，研究与发展总裁，Maze首席医疗官Harold Bernstein说：“虽然APOL1与肾脏疾病之间的遗传联系已经确立，但其诱导肾脏损伤的机制近十年来一直不确定。”。“通过这项研究和在Maze进行的早期研究，我们已经更好地了解了APOL1在肾脏疾病中的机制以及如何干预药物治疗。

Based on these findings, our lead program for APOL1 kidney disease was designed to phenocopy the protective variant, mimicking the protective characteristics of the p.N264K variant, as a potential disease modifying treatment for a large sub-population of patients suffering from kidney disease.”.

基于这些发现，我们针对APOL1肾脏疾病的主要计划旨在对保护性变体进行表型复制，模仿p.N264K变体的保护特性，作为针对患有肾脏疾病的大量亚群患者的潜在疾病缓解治疗“。

To further validate their finding, the researchers conducted a cross-sectional analysis of 121,492 participants of African ancestry from the Million Veterans Program to determine if the presence of p.N264K modified the association between the G1/G2 risk variants and CKD and ESKD. The results showed a clear association between p.N264K and a significantly reduced risk of CKD and ESKD among carriers of the G1/G2 risk variants compared to individuals with APOL1 high-risk genotypes.

为了进一步验证他们的发现，研究人员对百万退伍军人计划的121492名非洲血统参与者进行了横断面分析，以确定p.N264K的存在是否改变了G1/G2风险变异与CKD和ESKD之间的关联。结果表明，与具有APOL1高风险基因型的个体相比，p.N264K与G1/G2风险变异携带者中CKD和ESKD的风险显着降低之间存在明确的关联。

The results were further replicated by the researchers through analyses from the Vanderbilt University Biobank (n= 14,386) and the National Institutes of Health All of Us (n= 14,704). Variant functionalization studies in cell models were also conducted, which showed that APOL1 p.N264K blocked APOL1 pore-forming function and ion conductance and reduced toxicity of APOL1 high-risk mutations..

研究人员通过范德比尔特大学生物库（n=14386）和美国国立卫生研究院（n=14704）的分析进一步复制了结果。还进行了细胞模型中的变体功能化研究，结果表明APOL1 p.N264K阻断了APOL1的孔形成功能和离子电导，并降低了APOL1高风险突变的毒性。。

These findings further support Maze’s planned advancement of a small molecule APOL1 inhibitor program, which the Company plans to evaluate as a treatment for APOL1 kidney disease, with a Phase 1 trial anticipated to begin by the end of 2023.

这些发现进一步支持了Maze计划的小分子APOL1抑制剂计划的进展，该公司计划将其评估为APOL1肾病的治疗方法，预计第一阶段试验将于2023年底开始。

About Maze Therapeutics

关于迷宫疗法

Maze Therapeutics is a biopharmaceutical company harnessing the power of human genetics to transform the lives of patients. The Company is committed to developing breakthrough precision medicines for common diseases with large unmet medical needs. Maze has developed Maze CompassTM, a proprietary, purpose-built platform to leverage genetic variation and integrate the critical step of variant functionalization into each stage of therapeutic development.

Maze Therapeutics是一家利用人类遗传学力量改变患者生活的生物制药公司。该公司致力于开发突破性精准药物，用于医疗需求未得到满足的常见疾病。Maze开发了Maze CompassTM，这是一个专有的专用平台，用于利用遗传变异并将变异功能化的关键步骤整合到治疗开发的每个阶段。

Utilizing Maze CompassTM, the Company's strategy is to develop its therapies independently, in collaboration with major pharmaceutical companies, and through company formation. For more information, please visit mazetx.com, or follow us on LinkedIn and X..

利用Maze CompassTM，公司的战略是独立开发治疗方法，与主要制药公司合作并通过公司组建。欲了解更多信息，请访问mazetx.com，或在LinkedIn和X。。