The purpose of this project is to develop a new radiotherapy treatment modality that will substantially enhance the treatment of wet AMD with minimal toxicity to healthy tissue, leading to major improvement in visual acuity, decreased use of intravitreal injections of anti-VEGF agents, lower cost of treatment, and a substantially improved quality of life for patients. The new modality entitled """"""""Customizable Radiotherapy Enhancement (CuRE)"""""""" using gold nanoparticles will enable major highly localized amplification of radiation damage to the neovascular AMD disease cells with minimal normal ocular tissue toxicity. In order to accomplish this, a potent amount of gold nanoparticles (AuNP), acting as """"""""smart bombs"""""""" will be targeted specifically to the neovascular AMD (disease) endothelial cells (ECs) as demonstrated in published simulations by Harvard Medical School project partner. Once the AuNP home on to the disease ECs, a relatively small amount of radiation will be focused on the AuNP. The small radiation will induce (activate) the AuNP to emit electrons that will kill (blast) the disease cells with very minimal collateral damage and normal tissue toxicity. The radiation beam will be delivered using a recently developed radiotherapy device by the company project partner (Oraya Therapeutics Inc.) specifically suited for the treatment of neovascular AMD, but limited by normal tissue toxicity constraints. The use of AuNP as described above will circumvent these toxicity limitations enabling a potential breakthrough new treatment modality for neovascular AMD patients.
The specific aims i n phase I of the STTR, will establish feasibility of the new CuRE modality for circumventing these toxicity limitations during treatment. If Phase I is successful, Phase II will test the modality in preclinical (animal) models. If ultimately successful, the new Oraya CuRE approach could be extended beyond the treatment of wet AMD, as a novel approach for more effective highly targeted treatment of eye cancers: e.g. choroidal melanoma, whose endothelial cells can also be uniquely targeted by AuNP.

Public Health Relevance

The highest clinical significance of the new Oraya CuRE treatment modality is anticipated in achieving major reduction in the frequency/need of anti-VEGF injections for wet Age-related macular degeneration (AMD) patients with concomitant major improvement in visual acuity and quality of life. This highly targeted customizable treatment modality could become a highly effective treatment option for the millions of neovascular AMD patients in the U.S and around the world. If successful, the CuRE modality could be extended to enhance treatment efficacy for eye cancers e.g. retinoblastoma or choroidal melanoma.

National Institute of Health (NIH)
National Eye Institute (NEI)
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
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Special Emphasis Panel (ZRG1)
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Wujek, Jerome R
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Oraya Therapeutics, Inc
United States
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Brivio, D; Zygmanski, P; Arnoldussen, M et al. (2015) Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation. Phys Med Biol 60:9203-13
Ngwa, Wilfred; Kumar, Rajiv; Sridhar, Srinivas et al. (2014) Targeted radiotherapy with gold nanoparticles: current status and future perspectives. Nanomedicine (Lond) 9:1063-82