Efficacy of Injectable Gentamicin in Hereditary Ichthyosis

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.

Inclusion criteria

• Adult patients affiliated to a social insurance protection regimen.
• 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)
• 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)
• 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

• Cutaneous signs suggesting a surinfection
• Hypersensibility of active substance or one of the gentamicin excipients
• Administration of an aminoside in the previous 3 months
• Treatment with nephrotoxic or ototoxic medication in the previous 6 weeks
• 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
• Subjects >75 years (physiological impairment of kidney function)
• Left ventricular insufficiency
• Hypoalbuminemia
• Myasthenia
• History of necrosis at the injection site during previous treatment with aminosid
• Grade B or C cirrhosis according to Child-Pugh classification
• Nephropathy or other situation at risk of renal dysfunction
• Renal insufficiency with glomerular filtration rate < 60mL/min
• 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
• Patient who modify his keratolytic or emollient treatment in the last two weeks previous the inclusion visit
• Patient who modify his retinoid topic treatment in the month previous the inclusion visit
• Patient who modify his systemic retinoid treatment in the 3 months previous the inclusion visit
• Patient under guardianship, curatorship or deprived of their liberty
• Patient with pre-existing neuromuscular disease
• 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.