Intravitreal Injections in the Ovine Eye

Area of Science:

• Ophthalmology
• Gene Therapy
• Neurology

Background:

• Neuronal ceroid lipofuscinosis (NCL) is a group of rare genetic disorders affecting the nervous system.
• CLN5 NCL is a form of NCL that impacts retinal structure and function.
• Intravitreal (IVT) drug delivery is a common, minimally invasive method for treating ocular diseases.

Purpose of the Study:

• To detail the surgical protocol for IVT delivery of a viral vector gene therapy (AAV9.CLN5) to the ovine eye.
• To evaluate the efficacy of IVT gene therapy in maintaining retinal structure and function in sheep with CLN5 NCL.

Main Methods:

• Ovine model of CLN5 NCL received IVT administration of AAV9.CLN5 gene therapy in one eye.
• The contralateral eye served as an untreated internal control.
• Retinal structure and function were assessed up to 15 months post-treatment.

Main Results:

• Retinal structure and function were preserved in the IVT-treated eyes up to 15 months.
• Untreated eyes showed progressive functional decline and severe atrophy.
• The AAV9.CLN5 gene therapy product received IND clearance from the FDA in September 2021.

Conclusions:

• IVT delivery of AAV9.CLN5 gene therapy is effective in maintaining retinal health in a sheep model of CLN5 NCL.
• This approach offers a promising therapeutic strategy for CLN5 NCL and potentially other genetic retinal diseases.
• The established surgical protocol facilitates further research and clinical translation.