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Wiederherstellung des DFNB83 Hörvermögens

Ref-Nr: TA-MBM-BioT-2077-UMG


Kurzfassung

Unsere Technologie erlaubt die Wiederherstellung des Hörvermögens mit einer CaBP2 Gentherapie für DFNB83 Schwerhörigkeit. Ein Ein-Vektor System für CaBP2 (Ca+2 binding protein 2) wird direkt in die Cochlea eingeschleust. In CaBP2 knock-out Mäusen wurden innere Haarzellen transduziert und das Hörvermögen wiederhergestellt.


Hintergrund

Our technology restores hearing with a virus-mediated delivery of CaBP2 for a gene-therapy of DFNB83. A one-vector system for CaBP2 (Ca+2 binding protein 2) is delivered directly into the cochlea. In a CaBP2 knock-out mouse model we showed transduction of inner hair cells and restoration of hearing.


Bilder & Videos


Problemstellung

Ca2+ binding proteins (CaBP) influence inner hair cell (IHC) presynaptic Ca2+ signal and sound encoding. CaBPs prevent calmodulin (CaM)-mediated Ca2+ channel inactivation. Efficient IHC transmitter release requires very fast Ca2+ channel activation. Different CaBPs do have different main functions.

Mutations in CaBP2 cause hearing impairment DVNB93. Absence of CaBP2 in IHCs leads to hearing impairment in knock-out mice. Its absence causes a disruption in temporal precision of sound encoding. Hearing impairment DFNB93 is a human autosomal-recessive deafness. Patients suffer from a moderate-to-severe prelingual hearing impairment. Pharmacological drugs can not be used to restore hearing. Gene therapy promises restoration of hearing (i.e. introduction of intact copies of the defective gene in the affected cell population in the ear). Each monogenic hearing disease requires an individual therapeutical construct.


Lösung

AAV virus-mediated one-vector delivery of CaBP2 (Ca+2 binding protein 2) into the cochlea. Successfully in vivo tested showing a transduction of inner hair cells of the cochlea and recovery of hearing in CaBP2 knock-out mice.

IN VIVO PROOF OF CONCEPT

Postnatal injection of "wild-type" AAV2/1-Cabp2-P2A-EGFP. Construct was injected into scala tympani of the right ear of CaBP2LacZ/LacZ or control mice via the round window at p5-7. Hearing in the injected right ear was compared to hearing in the left non-injected ear. Four weeks after injection hearing was tested by auditory brainstem recordings (ABRs). The animals were then sacrificed; cochleae was isolated and used in patch-clamp experiments.


Vorteile

  • High specificity for DFNB9 deafness.
  • In vivo proof-of-concept successfully achieved. 

Anwendungsbereiche

Gene therapy of deafness DFNB93 for restoration of hearing.


MBM ScienceBridge GmbH

Dr. Stefan Uhle
0551-30724 154
suhle@sciencebridge.de
www.sciencebridge.de
Adresse
Hans-Adolf-Krebs-Weg 1
37077 Göttingen



Entwicklungsstand

Präklinik


Patentsituation

  • PCT anhängig

Stichworte

hörvermögen, DFNB83, CaBP2, gentherapie, schwerhörigkeit, Ca+2 binding protein, MBM ScienceBridge GmbH, Technologieangebot/technology offer, Technologietransfer/ technology transfer, Georg-August-Universität Göttingen/

Angebot Anbieter-Website


Kontakt | Geschäftsstelle

TechnologieAllianz e. V.
Christiane Bach-Kaienburg
(Geschäftsstellenleiterin)

c/o PROvendis GmbH
Schloßstr. 11-15
D-45468 Mülheim an der Ruhr