H2020Индивидуална стипендия2021–2023

PHERADOA · Pharmacological therapy to curtail visual loss in ADOA mouse model

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2021-11-12 → 2023-11-11
Финансиране от ЕС: 171 473 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Фармакологичната терапия при мишки с ADOA изследва как се намалява загубата на зрение, причинена от натрупване на автофагозоми. Разработването на такава целенасочена терапия помага за справянето с редките заболявания и носи социални и икономически ползи за обществото.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Pharmacological therapy to curtail visual loss in ADOA mouse model

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.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Autosomal dominant optic atrophy (ADOA) is the most common hereditary neuropathy that affects 1:35.000 people worldwide. A progressive visual loss is a characteristic of ADOA, and a treatment is not available. Mutations in the nuclear gene Optic Atrophy 1 (OPA1) in ADOA patients promote low levels of OPA1 protein, causing Retinal Ganglion Cells (RGCs) degeneration leading to blindness. OPA1 is the key component for mitochondrial inner membrane fusion mechanism and controls cristae biogenesis and remodeling, affecting cytochrome c release and apoptosis. So, mutations in OPA1 in RGCs may affect mitochondria integrity and lead to insufficient energy supply in the optic nerve. The role of OPA1 in ADOA-RGCs remains elusive since ADOA mouse models show inconclusive and no RGCs specific results. To address this issue, Dr. Luca Scorrano developed an ADOA mouse model of conditional RGCs OPA1 depleted. In this model, RGCs show fragmented mitochondria and excluded from axon but combined with autophagosomes in the axonal hillock. But a genetic autophagy inhibition restores mitochondrial distribution in the RGCs axon and curtails visual loss in the ADOA animal. These data suggest that autophagosome accumulation reduced axonal mitochondria content in RGCs by an impairment of the mitochondrial traffic. Therefore, we propose that visual loss of ADOA mouse model will be prevented by restoring its axonal mitochondrial content through a local use of inhibitors of the autophagy process. This proposal aims to develop a pharmacological therapy to curtail ADOA mouse visual loss. For this, we will deliver autophagy inhibitors through vitreal nanocarriers implants in ADOA mouse model which is conditional RGCs-OPA1 depleted. This research will contribute to provide a pre-clinical approach for a potential pharmacological therapy to ADOA patients.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITA DEGLI STUDI DI PADOVA · PadovaКоординаторИталия