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Nanoparticle-mediated ocular delivery of novel NAD-boosting small molecules for ophthalmic disease.

Objective

Metabolic decline may be a critical, and treatable, pathogenic component of glaucoma. Glaucoma is one of the most prevalent neurodegenerations worldwide, affecting 80 million patients worldwide. There are no neuroprotective therapies.
We have discovered metabolic and mitochondrial dysfunction in the retina and optic nerve which occur prior to neurodegeneration in glaucoma. One of these early changes is a decline in the important metabolite nicotinamide adenine dinucleotide (NAD), which critically regulates neuronal survival in glaucoma. Preventing NAD decline pharmacologically or through targeted gene therapies robustly prevents neurodegeneration. We are now actively generating novel NAD-generating compounds based on our initial studies. Neuronal NAD production is an ideal target for neuroprotective drug discovery for neuroprotection in glaucoma and other axon degenerations.
The goal of this research project is to develop clinically translatable nano-enabled neuroprotective strategies for glaucoma. I will focus on these novel strategies involving compounds that increase NAD metabolism developed by the Williams lab and formulated in nanocarriers by the Sotiriou lab. These will be translated into practical, effective agents that provide long-term effects in the retina. The current challenges we face are: (1) ocular delivery without toxicity, (2) high pay-load delivery, (3) delivery with sustained release. To overcome these, the Williams and Sotiriou labs will collaborate, where I will: (1) rationally design biocompatible nanocarriers by flame spray pyrolysis, (2) load these nanocarriers with novel NAD-generating drugs, (3) evaluate their NAD-generating capacity in vivo and the resulting neuroprotective effects. With this project, I will combine the expertise from the two laboratories to facilitate the integration of visual neuroscience, pharmacology, and nanoscale drug delivery systems to develop clinically translatable therapies for ophthalmic disease.

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Programme(s)

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

KAROLINSKA INSTITUTET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 252 180,00
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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