Interleukin (IL)-34 is a homodimer that is produced mainly by keratinocytes, neuronal cells and regulatory T cells (Tregs). It is believed to play important roles in chronic inflammation and the homeostasis of microglia. Currently, there is no effective treatment for many types of retinal degeneration. An improved treatment of autoimmune uveitis is also needed, as current uveitis treatment primarily uses steroidal anti-inflammation medication, which may produce significant unwanted side effects in long-term use. The inventors at the National Eye Institute (NEI) found that various retinal degeneration and uveitis models in mice with congenital mutations affecting vision have varying degrees of IL-34 deficiency in their intraocular environment. This suggests that IL-34 may be essential in modulating autoimmune uveitis and retinal degeneration. Therefore, Adeno-associated Virus (AAV) AAV8-IL-34-mediated gene therapy or other extended delivery methods of IL-34 protein to the eyes of patients with uveitis or retinal degeneration is a promising strategy for reducing retinal damage caused by ocular inflammation or degeneration and counteracting vision loss. AAV8 is a promising delivery method, as it preferentially infects retinal cells.

Competitive Advantages:

• Abrogates the need for chronic steroid use in uveitis, diminishing the risk of side effects from long-term use 
• AAV8 preferentially infects retinal cells; therefore, it could be a good choice for IL-34 gene therapy of uveitis for improved efficacy 
• Potential platform approach to the more than 200 inherited retinal dystrophies (IRDs) associated with progressive retinal degeneration. 
• A regulatory path to approval now exists: the first FDA-approved gene therapy, voretigene neparvovec (Luxturna; Spark Therapeutics) was already approved by FDA and the European Medicines Agency (EMA) in November 2018. 
• IRDs are strong candidates for gene therapy when causative mutations have been identified and, to some degree, the eye is an immune-privileged space. 
• In clinical trials, no significant immune reactivity or systemic adverse events have been associated with the AAV as gene delivery vehicle.

Commercial Applications:

• New therapeutic approach for uveitis and retinal degenerative diseases.