Valerio Carelli, Convegno Mitocon 2013

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Risultati sull'uso dell'EPI-743 in diverse sindromi in pazienti adulti
Valerio Carelli, Università di Bologna

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Valerio Carelli, Convegno Mitocon 2013

  1. 1. Terapia con EPI-743 inpazientiadulti (LHON e NARP)Valerio Carelli, MD, PhDLaboratorio di Neurogenetica, Dipartimento diScienzeBiomedicheeNeuroMotorie (DIBINEM),Universita’ di BolognaIRCCS Istituto di ScienzeNeurologiche di Bologna,OspedaleBellaria, Bologna
  2. 2. LHONND1 (3460)ND4 (11778) ND6 (14484)Difetto del Complesso I
  3. 3. STORIA NATURALE DELLA LHONBarboni et al., Ophthalmology 2010
  4. 4. Pattern specifico di neurodegenerazione
  5. 5. Questo pattern e’caratterizzatodallavulnerabilita’dellefibrenervose a calibrominore
  6. 6. 63
  7. 7. CONTROLLO LHON/3460
  8. 8. • Females may be partially protected from LHONby estrogens,which activate mitochondrialbiogenesis• Increased mitochondrial biogenesis is asuccessful compensatory strategy thatinfluences penetrance (now we are hunting thenuclear modifying genes relevant to thismechanism)• Estrogen-like drugs and strategies to increasemitochondrial biogenesis may be relevant fortherapy
  9. 9. RECUPERO DI FUNZIONEVISIVA
  10. 10. TERAPIA PER LA LHON• Idebenone and EPI-743• Anti-apoptotic drugs for acute phase• Activation of mitochondrial biogenesis forcarriers• Gene therapy: allotopic expression• Gene therapy: xenotopic expression ofalternative oxidase (S. Cervisiae singlesubunit NADH oxidase Ndi1)
  11. 11. Idebenone
  12. 12. CONCLUSIONSIdebenone treated patients with the 11778/ND4mutation had significantly increased rate ofvisual recovery compared to untreatedThe duration of therapy was longer for patientsrecovering vision and earlier start of therapycorrelated with earlier onset of visual recovery “in-between eyes” idebenone treatment did notspare the second eye
  13. 13. EPI-743
  14. 14. Complete reversion Partial recovery ProgressionLHON patients treated with EPI-743 at Doheny Eye Institute(courtesy Prof. Alfredo A. Sadun)
  15. 15. Trepazientiitalianitrattati con EPI-743• 300 mg x 3/die• Stadioprecoce di malattia, con coinvolgimentosolo monolaterale• Due con mutazione 11778/ND4 euno con3460/ND1
  16. 16. PATIENT 1 – LHON/3460
  17. 17. PATIENT 2 – LHON/11778
  18. 18. Patient 3 – LHON/11778
  19. 19. Perinatal hypoxia:hemianopsia at visual field
  20. 20. Lactic acid after standardizedeffort is ameliorated byEPI-743
  21. 21. Conclusioni• 1 paziente con recuperoparziale• 1 pazientesenzarispostaterapeutica• 1 paziente con recuperoerisparmio delsecondoocchio• Neipazienti USA (n=12) stessapercentuale disuccessoterapeutico (2 casi concompletaregressionedellamalattiaeassenza diperdita di fibre=malattiaabortita)• NeipazientiBrasiliani (n=6), tutti conmalattiacronica, 2 hannobeneficiato di unrecupero di funzionevisiva
  22. 22. Unafamiglia NARP (3 pazienti) trattatacon EPI-743 da circa 8 mesi
  23. 23. Ax 3D FSPGR T1 Ax FLAIR T2 Cor FSE T2PRE- EPI 743POST- EPI 743(3 mesi)
  24. 24. Ax T2FSE Ax T2 FLAIR Cor FSE T2POST-EPI 743( 7 mesi)
  25. 25. Lab of Neurogenetics:-Valerio Carelli, MD, PhD-Maria Lucia Valentino, MD-Chiara La Morgia, MD, PhD-Sabrina Farne, lab technician’-Luisa Iommarini, BiotechSc-Leonardo Caporali, BiotechSc-Alessandra Maresca, BiotechSc

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