Novel Compounds targeting GAPDH-Siah Cell Death Cascade

Novel Compounds targeting GAPDH-Siah Cell Death Cascade

JHU Ref #: C11114

Value Proposition

• Targeted therapy:  Small molecule compound that inhibits the GAPDH-Siah cell cascade to prevent cell death in degenerative diseases
• Broad Application: Effective across stress-mediated conditions, including Alzheimer’s, Parkinson’s, stroke, heart disease, and psychiatric disorders.
• Cytoprotection: Blocks cell death without disrupting normal metabolic functions, offering safer and more effective treatments.

Technology Description

• Researchers at Johns Hopkins University have developed novel chemical compounds that inhibit the glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-Siah cell death cascade. The GAPDH-Siah pathway is activated during cellular stress, leading to neurodegeneration, heart failure, and other stress-mediated disorders. These compounds selectively block the nuclear translocation of GAPDH, offering a potential therapeutic approach for preventing cell death and degeneration in conditions like Alzheimer's, Parkinson's, and heart disease, without affecting normal cellular functions.

Unmet Need

• Stress-mediated disorders, including neurodegenerative diseases, psychiatric conditions, and cardiomyopathy , are global health challenges with limited therapeutic options. . Current treatments often fail to address the underlying molecular pathways responsible for stress-induced cell death.. There is a critical need for cytoprotective agents that can specifically target these pathways to prevent disease progression.

Stage of Development

• Pre-Clinical

Data Availability

• Available upon request.

Publication

• Molecular Psychiatry volume 29, pages2967–2978 (2024)

• Nuclear GAPDH cascade mediates pathological cardiac hypertrophy | bioRxiv