RHO-CURE

Development of pharmacological treatment options to halt retinal degeneration caused by dominant rhodopsin mutations

15/09/2018 to 14/03/2021

Inherited retinal degenerations (RD) are blinding diseases caused by mutations affecting the light sensing photoreceptors. This leads to an irreversible loss of photoreceptors and vision, and to date, these diseases are still untreatable. Two metabolic networks stand out as particularly interesting for therapy development, namely disturbances in proteostasis and aberrant cGMP-signaling. Mutations causing a disruption of the phototransduction cascade typically result in a dysregulation of cGMP-signaling, while mutations affecting the proper folding of proteins cause pertinent cellular stress. Mutations in the rhodopsin gene stand out because they may activate both degenerative pathways. Here, we are proposing to develop treatment approaches addressing the degenerative effects of rhodopsin mutations in their entirety. The objective is to build a preclinical rationale to restore protein homeostasis and/or inhibiting cGMP-signaling to specifically treat the Ile-256del mutation in the rhodopsin gene.