ENGINEERED MICROBIAL THERAPEUTICS FOR METHIONINE RESTRICTION TREATMENT OF HERITABLE FORMS OF GLIOMA.

长期以来，全身性蛋氨酸水平一直与癌症的发生和发展有关，细胞代谢的变化使肿瘤细胞对氨基酸缺乏敏感。Petri Bio，Inc.开发了一种新的治疗策略，使用微生物组兼容的细菌菌株作为代谢酶的表达载体。该公司的领先产品是一种活的生物治疗微生物，它能产生可口服的蛋氨酸降解酶，在蛋氨酸被胃肠道系统吸收之前减少膳食中的蛋氨酸。在这里，Petri Bio公司将在匹兹堡大学博士Sameer Agnihotri的实验室开发的弥漫性中线胶质瘤(DGM)和弥漫性包含性脑桥胶质瘤(DIPG)的小鼠模型中评估这种候选治疗方法。阿格尼霍特里博士的工作表明，被改造为携带组蛋白3基因特定突变的小鼠对蛋氨酸高度敏感。组蛋白3基因已知是导致儿童患者DGM/DIPG的原因。携带肿瘤的小鼠在蛋氨酸限制性饮食中表现出显著的延长寿命，这一策略与人类患者的依从性差和最低有效性有关。在这个小鼠模型系统中，成功地证明了PETRI Bio的方法减少了肿瘤负担并延长了寿命，这将为继续开发和最终商业化提供令人信服的可行性数据。

Systemic methionine levels have long been implicated in cancer disease onset and progression, with changes in cellular metabolism rendering tumor cells sensitive to amino acid deficiencies. Petri Bio, Inc. has developed a novel therapeutic strategy, using microbiome-compatible bacterial strains as expression vectors for metabolic enzymes. The company’s lead product is a live biotherapeutic microbe which produces methionine degrading enzymes that can be taken orally, reducing dietary methionine before it is absorbed by the gastrointestinal system. Here, Petri Bio, Inc. will evaluate this candidate therapeutic in a murine model of form of diffuse midline glioma (DGM), diffuse inclusive pontine glioma (DIPG), developed in the laboratory of Sameer Agnihotri, PhD of the University of Pittsburgh. Dr. Agnihotri’s work indicates that mice engineered to carry specific mutations in the histone 3 gene known to be responsible for DGM/DIPG in pediatric patients, are highly sensitive to methionine. Tumor-bearing mice exhibit significantly increased lifespans when on a methionine-restrictive diet, a strategy associated with poor adherence and minimal effectiveness in human patients. Successfully demonstrating that Petri Bio’s approach reduces tumor burden and extends life span in this murine model system will provide compelling feasibility data toward continued development and eventual commercialization.