Massachusetts Institute of Technology

Whitehead Institute for Biomedical Research

Howard Hughes Medical Institute

Dan Yi Gui

David Sabatini

Alexander Muir

Laura Danai

Kivanc Birsoy

Matthew George Vander Heiden

Matthew Vander Heiden

Lucas Bryan Sullivan

The invention relates to methods and related compositions for enhancing cancer therapy and in particular glutaminase inhibitor therapy. The methods involve methods for identifying patients susceptible to glutaminase inhibitor therapy as well as sensitizing patients to glutaminase inhibitor therapy.

Methods and products related to glutaminase inhibitors

Provided herein are methods, compositions, and systems for treating mitochondrial disorders (e.g., MERRF, MELAS, Kearns-Sayre syndrome, chronic progressive external ophthalmoplegia, diabetes mellitus and deafness, lactic acidosis, Leber's hereditary optic neuropathy, Wolff-Parkinson-White syndrome, Leigh syndrome, NARP, myoneurogenic gastrointestinal encephalopathy, mitochondrial DNA depletion syndrome) or neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease) by administering aspartate, or an analog or prodrug thereof, or an agent that increases intracellular levels of aspartate. Pharmaceutical compositions and kits for use in treating mitochondrial disorders and neurodegenerative diseases are also described herein. Also provided are methods for treating disease by modulating the redox state of a cell, and methods of treating a proliferative disease by administering a cytosolic aspartate aminotransferase (GOT1) inhibitor.

Therapeutic strategies for treating mitochondrial disorders

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Cambridge, MA, United States of America

Dan Yi Gui