Nanoparticle-based immunization, a novel therapeutic strategy for amyotrophic lateral sclerosis

Project Information

NanoALS

Grant agreement ID: 752349

DOI

10.3030/752349

Project closed

EC signature date 3 March 2017

Start date 1 March 2018

End date 29 February 2020

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 158 121,60

EU contribution

€ 158 121,60

Coordinated by

UNIVERSIDAD DE ZARAGOZA
Spain

Periodic Reporting for period 1 - NanoALS (Nanoparticle-based immunization, a novel therapeutic strategy for amyotrophic lateral sclerosis)

Reporting period: 2018-03-01 to 2020-02-29

Summary of the context and overall objectives of the project

As the life span of the population extends, the prevalence of neurodegenerative diseases is rapidly increasing representing a considerable impact for the quality of life and economy of many countries worldwide. Therefore, looking for common therapeutic strategies is essential to optimize time and resources to tackle neurodegenerative diseases.
Gene therapy, and particularly the novel Crispr Cas9 technology, has been shown effective in ameliorating most of these diseases, including Amyotrophic lateral sclerosis (ALS), however delivering these gene editing tools into Central Nervous System cells represents a burden to translate these therapies into clinical practise.
The aim of NanoALS was to bring together Neuro and Nanoscience fields to design a novel nanoparticle to deliver Cas9 and sgRNA components to correct SOD1 mutations in ALS.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Under NanoALS workframe, gold and PLGA polymer nanoparticles were assembled to encapsulate Cas9 and sgRNA components. Synthesis procedures were deeply optimized to increase encapsulation efficiency and preserve nucleic acid integrity. Nanoparticle size was maintained below 180 nm (for PLGA) and 15 nm (for gold) to facilitate blood brain barrier penetration. Subsequently, viability and cell cycle assays demonstrated the biocompatibility for motor neurons and subcytotoxic doses were calculated. A rapid cell- uptake was observed for both nanoparticles starting from 8h with a maximal rate at 24h. Finally, capacity of these nanoconstructs to knock-down SOD1 expression was demonstrated in motor neurons in vitro cell models. Further experiments are ongoing to demonstrate efficacy in vivo.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Based on the combined action of Nanoengineering and Neuroscience, NanoALS team has designed a novel carrier to efficiently deliver the potent gene editing tool Cas9 into motor neurons. This Cas9 system has previously demonstrated the ability to correct mutations, delaying disease progression and extending the lifespan of amyotrophic lateral sclerosis animal models.
The World Health Organization estimated in 2007 that 24 million people in the world were affected by neurodegenerative diseases, with 6.8 million of deaths per year and a rising impact on the quality of life and economy of European countries (estimated in about 139 billion euros in 2004). Currently, no cure exists for these disorders although gene therapy has showed great potential by correcting mutations, boosting or blocking specific mechanisms.
By adapting the sgRNA sequence to target different genes and mutations, nanoparticles designed during NanoALS have the potential to be used in these neurodegenerative diseases.

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