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VisionRe Novel therapy targe?ng mitochondrial dysfunc?on in LHON Overview LHON is the most common mitochondrial disorder in humans. Mitochondria are powerhouses of the cell producing energy (ATP). No effecAve therapies exist for LHON. LHON causes extreme visual disability due to loss of reAnal ganglion cells & atrophy of the opAc nerve. Typically affects males between 2nd-­‐4th decades. MutaAons in different regions of mitochondrial DNA encoding Complex I cause LHON. Delivery to mitochondria is challenging as each cell has hundreds of mitochondria. TCD’s novel technology circumvents these problems using a nuclear gene whose product mirrors the funcAon of Complex I. The Complex I subsAtute can be transported to mitochondria. The therapy compensates for the mitochondrial deficiency present in LHON. Significant benefit demonstrated in animal model. Problems Solved by the Strategy Therapeu,c Strategy
Commentary adapted from New ScienAst June 2012… ‘Using gene therapy to fix glitches in mitochondrial DNA is challenging, not least because the therapy must be delivered to the many mitochondria in each cell. The team in Trinity College Dublin has demonstrated a workaround. They target the cell’s nucleus instead, encouraging it to produce Complex-­‐I type proteins, which then enter the many mitochondria in the cell.’ Benefit to PaAent
Single intravitreal injecAon of AAV Therapy
AAV can infect the target re,nal cells
Market TherapeuAcs: Synthesis, FormulaAon< Processing and Drug Delivery IP Status NaAonal filings July 2014 US, EU, Canada, Australia, New Zealand EU 11194976 Opportunity Green areas represent target cells infected with therapeuAc AAV
Research collaboraAon, Available to license
Technology and Patent Status High Atre recombinant AAV with the Complex I therapy is produced in HEK293 cells. Clear development pathway involving GMP producAon of AAV required for toxology/biodistribuAon & human clinical trial. LHON paAent with opAc nerve changes
Advantages over Exis,ng Technologies •  Therapy represents a single soluAon for LHON which has mulAple causes •  Circumvents the difficulAes of delivering therapies to mitochondria •  A single intravitreal injecAon of virus (AAV) with the therapy provides long term benefit •  AAV shown to be well tolerated in human eye Patent filed: European Patent ApplicaAon No 11194796 PublicaAons: Commentary New ScienAst June 2012; Chadderton et al. 2013 EJHG 21: 62-­‐68. The opportunity The technology & associated AAV product is in preclinical development with clear benefit obtained. The technology is well suited to a start up company or licensing opportuniAes. Please contact us if you would like further informaAon on the development of this novel technology. Researcher(s) Farrar, GJ Chadderton, N Millington-­‐Ward, S Contact Dr. Gordon Ellioi, Case Manager, TranslaAonal Sciences [email protected] +353 1 896 4151 Reference: JF01-­‐325-­‐01