Pharmacological therapy to curtail visual loss in ADOA mouse model

Informations projet

PHERADOA

N° de convention de subvention: 101030965

DOI

10.3030/101030965

Projet clôturé

Date de signature de la CE 29 Mars 2021

Date de début 12 Novembre 2021

Date de fin 11 Novembre 2023

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 171 473,28

Contribution de l’UE

€ 171 473,28

Coordonné par

UNIVERSITA DEGLI STUDI DI PADOVA
Italy

Periodic Reporting for period 1 - PHERADOA (Pharmacological therapy to curtail visual loss in ADOA mouse model)

Période du rapport: 2021-11-12 au 2023-11-11

Résumé du contexte et des objectifs généraux du projet

The problem addressed is the visual loss of ADOA patients, mediated by an accumulation of autophagosomes. This is important to society because developing a targeted therapy to ADOA raises awareness of rare diseases and offer benefits at the economical, emotional, and social level to European society. The specific scientific and training objectives described in PHERADOA project were:

1.Gain and disseminate knowledge of all aspects of mitochondrial biology by participating in the weekly mitochondrial seminars called “Mito-Meetings”.
2.Enhance communication and presentation skills by conducting monthly seminar presentations to report new research findings to laboratory group.
3.Expand knowledge in microscopy trained by permanent staff scientists to use the high-tech equipment of the institutions.
4.Training in drug delivery formulation and characterization.
5.Training on manipulating/caring and microsurgery in animals.
6.Enhance my communication skills through writing manuscripts, attending conferences, and performing outreach activities.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

1.The project steps developed are:
WP1. Prepare controlled drug delivery systems for the treatment of ADOA: Characterize drug polymer bio-conjugates (DPBs) by analytical tools and investigate autophagy inhibitors delivery in vitro using primary RGCs.(Full performed)
WP2. Evaluate the tolerability of drug delivery intravitreal implants in wild-type animals: Verify if animals tolerate intravitreal implants to release the potential ADOA drugs in wild type (WT) animals. (Full performed)
WP3. Measure the efficacy of tolerated intravitreal implants releasing autophagy inhibitors incurring visual loss in the ADOA mouse: The WP3 will measure the efficacy of tolerated drugs from WP2 against ADOA mouse to curtail visual loss. (Partially performed)

- Results
a. main scientific and/or technological achievements:
(1) Obtained the characterization of the drug polymer bio-conjugate (PLGA-FK506);
(2) Mice are tolerable to intravitreal treatment over 6 months;
(3) ADOA mice models under DPBs treatment do not lose visual acuity when in treatment over 6 months.

Overview of the results: Our project demonstrate the maintenance of visual acuity mediated by the PLGA-TAC treatment over 6 months in mouse ADOA models. It shows that genetic and pharmacological approaches can be used to treat ADOA visual loss.

2.Exploitation and dissemination of results:
a)List the conferences attended for scientific community:
- Third International GIBB Meeting, Riva del Garda (IT), 2023.
- The XXI Scientific Convention, Riva del Garda (IT), 2023.
- MCAA Annual Conference and General Assembly, Sevilla (ES), 2023.
- Retina 2022, Dublin (IE), 2022.
- Open World Conference 2022, Copenhagen (DK), 2022.
- EMBO Workshop Autophagy in brain health and disease, Sant Feliu de Guíxols (ES), 2022.

b)List all the outreach activities undertaken:
- Twitter laboratory account to share project updates.
- Development of a virtual community for sharing knowledge about rare diseases.
- Presentations in department aiming to guide researchers to apply for Horizon 2020 projects.
- Part of eLife Science Ambassadors remotely.
- Member of Communication Chapter group of Marie Curie Alumni Association, within 6 articles for general public published online and reaching out to all MSCA researchers worldwide.

c)List all trainings, both for technical and soft skills
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d)List of conferences attended

PS: All the past/current/future activities related to the project MSCA fund has been/will be acknowledged.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The results show the treatment can be a pharmacological therapy for ADOA patients who suffer from a rare, understudied, and untreatable disease; It also demonstrate an innovative drug-polymer conjugates (PLGA-TAC) safely and efficaciously delivered drugs to treat a chronic condition that affects RGCs; and open doors to explore two understudied fields - ocular drug delivery and a rare genetic mitochondrial disease.
a. main innovation outputs:The development of the first ocular treatment based on drug polymer conjugation for ADOA patients.
b. contribution to the state of the art:Results demonstrate the maintenance of visual acuity mediated by the PLGA-TAC treatment over 6 months in mouse ADOA models. It shows that genetic and pharmacological approaches can be used to treat ADOA visual loss.
c. scientific and/or technological quality of the results: This research provides a pre-clinical approach for a potential pharmacological therapy for ADOA patients, and we have positive results.

The researcher career impact is:

a. The researcher will look for the possibility of applying for national grants in Italy to further develop the project at the same institution.
b. The project also allowed the researcher to network with patient groups or NGOs, where she could advocate for rare diseases or develop training and team capacity building.

ADOA mouse model mechanism