efficacy of injectable gentamicin in hereditary ichthyosis

Conditions: Ichthyosis

Summary: this study will evaluate the efficacy and safety of intravenous gentamicin in congenital ichthyosis due to a non-sens mutation. the primary objective is the severity of scales and erythema at the third month, compared to baseline. secondary objectives will include: the importance of itching, trans epidermal water loss, cutaneous expression of the targeted protein, the security of the drug and patients' satisfaction.

congenital ichthyoses represent a group of diseases characterized by disabling cutaneous anomalies (scales and inconstant erythema) often associated with extra cutaneous anomalies that may be severe. the treatment is non curative and symptomatic, including local treatments (ie. emollients). oral retinoids may be helpful in moderate to severe forms. there is a huge need for novel therapies, ideally targeting the molecular defect. gentamicin may be a novel therapeutic option for congenital ichthyosis. apart its antimicrobial effect, gentamicin can achieve stop codon readthrough and produce full-length protein. in this study, gentamicin (10 mg/kg) will be administrated once weekly for 3 months. the study will include monthly visits, a follow-up visit 3 months after the stopping the drug and an end-of-study visit 3 months after the follow-up visit. kidney and hearing functions will be assessed regularly.

Eligibility criteria:
inclusion criteria: 1. adult patients affiliated to a social insurance protection regimen. 2. hereditary ichthyosis caused by a homozygous non-sense mutation of a gene responsible for hereditary ichthyosis (tgm1, pnpla1, alox12b, nipal4, aloxe3, sdr9c7, abca12, cers3, spink5 and cdsn) 3. moderate to severe forms of ichthyosis defined as validating an ichthyosis severity index score at 2-3 on at least 2 out of 4 areas evaluated (back, upper limbs, lower limbs, back of the foot) 4. free, informed consent, written and signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research). exclusion criteria: 1. cutaneous signs suggesting a surinfection 2. hypersensibility of active substance or one of the gentamicin excipients 3. administration of an aminoside in the previous 3 months 4. treatment with nephrotoxic or ototoxic medication in the previous 6 weeks 5. pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study. women of childbearing age, potentially sexually active, and unwilling to use acceptable contraception measures in accordance with clinical trials facilitation and coordination group recommendations 6. subjects \>75 years (physiological impairment of kidney function) 7. left ventricular insufficiency 8. hypoalbuminemia 9. myasthenia 10. history of necrosis at the injection site during previous treatment with aminosid 11. grade b or c cirrhosis according to child-pugh classification 12. nephropathy or other situation at risk of renal dysfunction 13. renal insufficiency with glomerular filtration rate \< 60ml/min 14. surdity which is not caused by plug scales in the external ear canals or other situation at risk of surdity including the presence of the a1555g mutation in the 12s ribonucleic acid (mitochondrial deoxyribonucleic acid) gene 15. patient who modify his keratolytic or emollient treatment in the last two weeks previous the inclusion visit 16. patient who modify his retinoid topic treatment in the month previous the inclusion visit 17. patient who modify his systemic retinoid treatment in the 3 months previous the inclusion visit 18. patient under guardianship, curatorship or deprived of their liberty 19. patient with pre-existing neuromuscular disease 20. patient participating in another clinical study with investigational treatment exclusion criteria at the end of the "run-in" period: variation greater than 15% in the validating an ichthyosis severity index score between two baseline measurements.

Keywords: congenital ichthyoses injectable gentamicin