TargetVPC

Towards clinical translation of mutation-independent treatment of RD by inhibiting VCP

01/07/2023 to 30/06/2025

To date, almost all forms of retinal degeneration (RD) are untreatable and lead to visual impairment and even blindness. Based on significant experimental data, we have reason to believe that disturbances in the dynamic regulation of a functional proteome (the proteostasis) and energy deficiency are common features of RD. Given the high energy demands of photoreceptors, chronic disturbances of cellular protein and metabolic homeostasis inevitably lead to dysfunction, energy deficiency and eventually their degeneration. We have identified "valosin-containing protein" (VCP), an enzyme of energy metabolism (ATPase) essential for the very energy-consuming process of degrading misfolded proteins, as an important therapeutic target.

Restoring the balance of proteostasis by inhibiting VCP with three VCP inhibitors improved photoreceptor viability and function in different animal models of RD. We now aim to further develop this preclinical proof of concept to identify and validate a superior VCP-targeting drug for future human clinical use.