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

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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.