An employee at Gyroscope Therapeutics Limited works at his computer. Gyroscope is a global organization with offices in London, San Francisco, and Philadelphia.
By Rebecca Salowe
Scheie Vision Summer 2021
In December 2020, Gyroscope Therapeutics Limited announced a research agreement with the University of Pennsylvania (UPenn) and Penn Center for Advanced Retinal and Ocular Therapeutics (CAROT) to develop gene therapies for three blinding eye diseases.
The team at UPenn will be led by four investigators with expertise in ocular gene therapy: Jean Bennett, MD, PhD, F.M. Kirby Professor of Ophthalmology; Ken Shindler, MD, PhD, Associate Professor of Ophthalmology; Ahmara Ross, MD, PhD, Assistant Professor of Ophthalmology; and Paris Margaritis, DPhil, Research Assistant Professor of Pediatrics at Children’s Hospital of Philadelphia.
Dr. Bennett, who serves as the Co-Director of CAROT, pioneered the research that led to the first FDA-approved gene therapy for an inherited disease. This gene therapy successfully restored vision in children and adults with a retinal degeneration caused by mutations in the RPE65 gene. For this accomplishment, Dr. Bennett was the co-recipient of the 1M euro Champalimaud Vision Award, $1M Sanford Lorraine Cross Award, and $1M Sanford and Susan Greenberg Outstanding Achievement Prize.
Dr. Shindler and Dr. Ross have extensive experience establishing SIRT1 as a key target for preventing optic nerve degeneration. They showed that gene therapy using SIRT1 as a therapeutic target enhances cell survival pathways after inflammatory, compressive, and glaucomatous damage to the optic nerve. Most recently, they published a study demonstrating that cell-specific delivery of SIRT1 gene therapy can rescue retinal ganglion cells in optic nerve injury.
“Together, these experiences will help us to advance the potential of gene therapies to treat multiple eye diseases,” said Dr. Shindler.
Gyroscope Therapeutics is a clinical-stage gene therapy company focused on eye diseases. Gyroscope’s lead investigational gene therapy, GT005, is being evaluated for its potential to slow progression of geographic atrophy secondary to dry age-related macular degeneration (AMD). This investigational therapy received Fast Track designation from the Food and Drug Administration and is currently in Phase II clinical trials.
The research collaboration with UPenn will focus on the development of gene therapies for optic neuritis, retinitis pigmentosa, and glaucoma. Gyroscope will have an exclusive option to the intellectual property associated with and resulting from the research conducted under this agreement.
“Currently, optic neuritis and retinitis pigmentosa do not have effective treatments to reduce vision loss, and glaucoma is a leading cause of irreversible vision loss worldwide due to treatment failure in many patients,” explained Dr. Shindler. “Development of novel treatments, therefore, holds tremendous potential to reduce vision loss."
The collaboration will harness the complementary expertise of Gyroscope and UPenn investigators.
“Gyroscope is an international company with expertise in benchwork science, fast-tracking investigational gene therapies, and moving an investigational gene therapy from preclinical models to clinical trials,” said Dr. Shindler. “Our investigators have expertise in pioneering retinal gene therapies and investigating the SIRT1 signaling pathway for neuroprotection.”
“This partnership will help to advance our pre-clinical work,” added Dr. Ross. “If the research proves to be positive, Gyroscope has the expertise to help bring these investigational therapies into the clinic.”
The teams hope to generate adeno-associated virus (AAV) technology for use in multiple retinal degenerations and optic neuropathies, regardless of their underlying genetic etiology. Most ocular gene therapies under investigation target a specific genetic mutation and cannot be used more broadly.
“By focusing on treatments that target pathways for neuroprotection in both optic nerve disease and retinitis pigmentosa, Gyroscope is expanding the potential for development of approaches that can be used to treat large numbers of patients suffering from devastating blinding diseases,” said Dr. Bennett.
“The prior success of Dr. Bennett’s gene therapy makes us extremely hopeful that our focus on a therapy that has shown early promise in preclinical studies, in collaboration with Gyroscope, may allow us to evaluate novel gene therapies aimed at a broad range of optic nerve and retinal diseases,” added Dr. Ross.