Pharmacological therapy to curtail visual loss in ADOA mouse model

Project Information

PHERADOA

Grant agreement ID: 101030965

DOI

10.3030/101030965

Project closed

EC signature date 29 March 2021

Start date 12 November 2021

End date 11 November 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 171 473,28

EU contribution

€ 171 473,28

Coordinated by

UNIVERSITA DEGLI STUDI DI PADOVA
Italy

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

Reporting period: 2021-11-12 to 2023-11-11

Summary of the context and overall objectives of the project

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.

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

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
-

d)List of conferences attended

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

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)

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