Alliance: The Invus Group

Despite growing knowledge around the genome alterations associated with glioblastoma, existing treatments have little therapeutic benefit and are aggressive, leaving patients suffering. Glioblastoma represents a particularly daunting problem because potential drugs need to penetrate the blood-brain barrier.

Paul Mischel sought to find an Achilles heel, a potential liability for the could serve as a target for potential drugs. They found their candidate in an enzyme called sphingomyelin phosphodiesterase 1 (SMPD1), upon which glioblastomas depend for survival. They found, remarkably, that the safe and highly brain-penetrant antidepressant fluoxetine (Prozac) potently inhibits SMPD1 activity and kills tumors in cell and mouse models. They also analyzed electronic health records and saw significantly increased survival in patients treated with fluoxetine, which was not seen in patients treated with other selective serotonin reuptake inhibitor (SSRI) antidepressants. These results suggested the SMPD1 is a promising new target for glioblastoma therapeutics with the potential to transform the lives of patients who currently have few options.

In collaboration with the IMA and the Invus Group, Mischel is developing new drug prototypes that target SMPD1.

Image credit: Vecteezy