Servicio de Información Comunitario sobre Investigación y Desarrollo - CORDIS

FP7

NO-MND Informe resumido

Project ID: 612578
Financiado con arreglo a: FP7-PEOPLE
País: Italy

Periodic Report Summary 1 - NO-MND (Transferring NOn autonomous cell degeneration models between EU and USA for development of effective therapies for Motor Neuron Diseases (MND).)

The NO-MND project addresses scientific questions related to “non autonomous cell death” in motor neuron disorders, by strengthening research partnerships through knowledge and staff exchanges, and networking activities between two European research organizations from Italy and Greece and one organization from the USA. Thus, the implementation of the NO-MND project is based on the consortium of three Academic subjects:
1) UNIVERSITA DEGLI STUDI DI MILANO (EU partner)
2) BIOMEDICAL RESEARCH FOUNDATION, ACADEMY OF ATHENS (EU partner)
3) TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK (Third Country)

No-MND objective
Amyotrophic lateral sclerosis (ALS) and Spinal Muscular Atrophy (SMA) are fatal diseases characterized by selective degeneration of motor neurons without any effective treatment. Non-neuronal cells like astrocytes play a key role in the pathogenesis of ALS and SMA. The overall objective of the project is to understand the mechanisms of cell death caused by non-neuronal cells as possible therapeutic target. Indeed, we are investigating the potential of non-neuronal cell transplantation as new treatment strategy for these disorders. These aims will be carried out in two research lines: 1) development of in vitro disease models to investigate molecular interactions between non-neuronal cells and motor neurons using cell reprogramming technology; 2) investigation of potential therapeutic efficacy of non-neuronal cell transplantation in motor neuron disease models.

Work program
NO-MND is articulated in six work packages. Work package (WP) 1 is concerned with overall project management and network coordination. WP 2 and 3 deal with in vitro studies of astrocytes reprogrammed from fibroblasts of ALS patients (WP2) and SMA (WP3) as an in vitro model and for therapy. We developed a fully humanized co-culture model composed of human sporadic MND astrocytes and human pluripotent stem-cell-derived MNs. WP4 and WP5 are focused on transplantation of glial restricted precursors (GRPs) derived from stem cells as a therapeutic strategy for ALS (WP4) and SMA (WP5). We are implementing a protocol for differentiation and selection of GRPs from induced pluripotent stem cells (iPSCs). WP6 is devoted to training, practice and dissemination activities.

Achievements
Thus far, the scientific achievements from the work packages are: WP1: successful networking and project organization. WP2: we have succeeded in creating a fully humanized in vitro model of ALS, and showed that astrocytes from sALS patients specifically kill pluripotent-MNs, whereas control astrocytes do not. WP3: we confirmed that human SMA motor neurons show a reduced survival in culture that can improved with restoration of SMN level by oligonucleotides or small molecules. The role of astrocytes in these events is under evaluation. WP4-5 we are optimizing the generation of glial restricted precursors (GRPs) derived from stem cells (iPSCs) and performed cell transplantation experiments using specific cell subpopulation in ALS/SMA models.
The NO-MND work packages have been implemented through highly successful researcher secondments between partners. Two international symposia and several meetings took place. Visitors gave research seminars, and overall participants contributed to 12 journal papers, and more than 12 abstracts, and presentations in more than 5 international conferences.

Benefits and outgrowth
NO-MND secondments and dissemination activities like seminars, workshops, jointly organized symposia, and collaborative writing of abstracts, and journal papers have generated numerous new contacts and interactions between the researchers from the participant Institutions and outside the Consortium. NO-MND knowledge exchange and networking resulted in a recent article on the implication of non-motor neuronal cells to SMA co-authored by all the partners. Participants have been able to focus their research activity to obtain expertise in iPSCs and cell transplantation protocols to improve existing technologies and creating new experimental settings for the treatment of MNDs. Bi-directional knowledge transfer between EU and Third country is crucially significant for strengthening this collaboration.

website: http://www.centrodinoferrari.com/laboratori/laboratorio-di-cellule-staminali-neurali/attivita-di-ricerca/mnd-7pq/?lang=

Contacto

MARIA ANTONIA GIOFRE', (Dept. Secretary)
Tel.: +390255184306
Correo electrónico
Número de registro: 184065 / Última actualización el: 2016-06-09
Fuente de información: SESAM