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Clinical trial of gene therapy with dual AAV vectors for retinitis pigmentosa in patients with Usher syndrome type IB

Objective

Usher syndrome (USH) is the most common combination of deafness and blindness due to retinitis pigmentosa. USHIB caused by mutations in the large MYO7A gene, is among the most severe and frequent forms of USH. While deafness can be improved with cochlear implants, blindness remains untreatable. Retinal gene therapy with AAV vectors is both safe and effective in humans, however it is limited by AAV cargo capacity which would not allow transfer of the large MYO7A expression cassette.
UshTher objective is to test the safety and efficacy of a highly innovative gene therapy approach (dual AAV) in the retina of USHIB patients. The projects builds on data previously obtained by the coordinator that a single combined subretinal administration of dual AAV vectors, each packaging one of the two halves of a MYO7A expression cassette, results in MYO7A reconstitution and therapeutic efficacy in a mouse model of USHIB. This has received the Orphan Drug Designation from the European Medicines Agency.
It would be the first time the dual AAV vector approach is tested in humans. Towards this ambitious objective, UshTher has assembled a very competitive consortium with leaders in the fields of retinal gene therapy from bench to bedside including SMEs with expertise in the development of gene therapy products. The planned activities span from manufacturing of clinical –grade dual AAV vectors to non clinical safety, biodistribution and expression studies performed under good laboratory practices up to performing a multicenter, multinational clinical trial which envisages subretinal administrations of dual AAV vectors in twelve USHIB patients.
UshTher success will set the basis for a cure for USHIB retinitis pigmentosa, and for testing dual AAV vectors in other rare and more common conditions which require delivery of large genes, thus overcoming one of the major limitations of in vivo gene therapy.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/mutation
  • /medical and health sciences/medical biotechnology/genetic engineering/gene therapy
  • /medical and health sciences/clinical medicine/ophthalmology
  • /medical and health sciences/medical biotechnology/medical bioproducts/implants

Call for proposal

H2020-SC1-2017-Two-Stage-RTD
See other projects for this call

Funding Scheme

RIA - Research and Innovation action

Coordinator

FONDAZIONE TELETHON
Address
Via Varese 16/B
00185 Roma
Italy
Activity type
Research Organisations
EU contribution
€ 1 783 642

Participants (8)

ASSOCIATION GENETHON
France
EU contribution
€ 91 068,75
Address
Rue De L Internationale 1 Bis
91002 Evry
Activity type
Research Organisations
GENOSAFE SAS
France
EU contribution
€ 527 952,50
Address
Rue De L'internationale 1
91000 Evry
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
UNIVERSITA DEGLI STUDI DELLA CAMPANIA LUIGI VANVITELLI
Italy
EU contribution
€ 700 567,33
Address
Viale Abramo Lincoln 5
81100 Caserta
Activity type
Higher or Secondary Education Establishments
INSTITUTO INVESTIGACION SANITARIA FUNDACION JIMENEZ DIAZ
Spain
EU contribution
€ 136 645,46
Address
Avenida De Los Reyes Catolicos 2
28040 Madrid
Activity type
Research Organisations
STICHTING OOGZIEKENHUIS ROTTERDAM

Participation ended

Netherlands
EU contribution
€ 0
Address
Schiedamse Vest 180
3011 BH Rotterdam
Activity type
Research Organisations
REITHERA SRL
Italy
EU contribution
€ 2 566 669,18
Address
Via Di Castel Romano 100
00128 Roma
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA
Italy
EU contribution
€ 54 525
Address
Piazza Dell'ateneo Nuovo 1
20126 Milano
Activity type
Higher or Secondary Education Establishments
HET ROTTERDAMS OOGHEELKUNDIG INSTITUUT BV
Netherlands
EU contribution
€ 137 445,53
Address
Schiedamse Vest 160 D
3011 BH Rotterdam
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)