Details

Autor(en) / Beteiligte

• Luo, Ling
• Zhang, Xiaohui
• Hirano, Yoshio
• Tyagi, Puneet
• Barabás, Péter
• Uehara, Hironori
• Miya, Tadashi R
• Singh, Nirbhai
• Archer, Bonnie
• Qazi, Yureeda
• Jackman, Kyle
• Das, Subrata K
• Olsen, Thomas
• Chennamaneni, Srinivas R
• Stagg, Brian C
• Ahmed, Faisal
• Emerson, Lyska
• Zygmunt, Kristen
• Whitaker, Ross
• Mamalis, Christina
• Huang, Wei
• Gao, Guangping
• Srinivas, Sangly P
• Krizaj, David
• Baffi, Judit
• Ambati, Jayakrishna
• Kompella, Uday B
• Ambati, Balamurali K

Titel

Targeted Intraceptor Nanoparticle Therapy Reduces Angiogenesis and Fibrosis in Primate and Murine Macular Degeneration

Ist Teil von

• ACS nano, 2013-04, Vol.7 (4), p.3264-3275

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Monthly intraocular injections are widely used to deliver protein-based drugs that cannot cross the blood-retina barrier for the treatment of leading blinding diseases such as age-related macular degeneration (AMD). This invasive treatment carries significant risks, including bleeding, pain, infection, and retinal detachment. Further, current therapies are associated with a rate of retinal fibrosis and geographic atrophy significantly higher than that which occurs in the described natural history of AMD. A novel therapeutic strategy which improves outcomes in a less invasive manner, reduces risk, and provides long-term inhibition of angiogenesis and fibrosis is a felt medical need. Here we show that a single intravenous injection of targeted, biodegradable nanoparticles delivering a recombinant Flt23k intraceptor plasmid homes to neovascular lesions in the retina and regresses CNV in primate and murine AMD models. Moreover, this treatment suppressed subretinal fibrosis, which is currently not addressed by clinical therapies. Murine vision, as tested by OptoMotry, significantly improved with nearly 40% restoration of visual loss induced by CNV. We found no evidence of ocular or systemic toxicity from nanoparticle treatment. These findings offer a nanoparticle-based platform for targeted, vitreous-sparing, extended-release, nonviral gene therapy.