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GenSight Biologics has reported recent research on how gene therapy transfer works migrating vectors from treated to control eyes.

In follow up the recent French Competent Authority granting of a Cohort Temporary Authorization for Use (“ATU de Cohorte” or ATUc) in July in 2021, for lenadogene nolparvovec (Lumevoq), sponsored by GenSight Biologics (Euronext: SIGHT), novel findings were reported this month in the journal “Molecular Therapy – Methods and Clinical Development“.  The results of a mechanistic study demonstrating the transfer of lenadogene nolparvovec from injected eyes to non-injected eyes of non-human primates has suggested that the vector might travel through an anatomic route via the optic nerve and chiasm, from treated to untreated eyes.  If formally proven, there may be a need to re-consider clinical study designs in some ocular research, specifically using treated and control studies in different separate groups of patients.  The current research in the journal commented that, “the demonstration of a transfer of the lenadogene nolparvovec active substance between eyes has major consequences for designing gene therapy clinical trials and should lead to prioritizing interpatient comparisons whenever possible”.


Lenadogene nolparvovec is to be used as a novel gene therapy for LHON, an inherited retinal degeneration with has an estimated prevalence of 1 in 40,000 in Europe. GenSight proposes that 1,100 to 1,200 LHON patients may be seeking therapies for this disorder each year.  The connection between LHON and mitochondrial DNA (mtDNA) arose following studies that reported a homoplasmic nucleotide transition from guanosine to adenosine at position 11778, resulting in an arginine-to-histidine substitution in ubiquinone oxidoreductase (NADH) subunit 4 (ND4) of the mitochondrial complex I.  It is now known that the majority of LHON cases are associated with mutations in one of three mitochondrial genes that encode subunits of the same complex I of the mitochondrial respiratory chain.  This complex I enzyme, containing 7 subunits encoded by mtDNA, is closely associated with the inner mitochondrial membrane, while a further 35 subunits, encoded by nuclear DNA, are imported into the organelle to facilitate specific steps of the respiratory pathway.


Following the recent study published in Molecular Therapy – Methods and Clinical Development, the lead author David J. Calkins, Ph.D, Professor & Vice Chair and Director for Research at the Department of Ophthalmology and Visual Sciences at Vanderbilt University Medical Center, noted that, “our study is a critical step towards understanding not only how bilateral improvement in vision occurs with unilateral gene therapy, but also mechanisms of interocular interactions more generally. Crosstalk between the two optic projections could have ramifications for additional blinding eye diseases”.