Absence of lenadogene nolparvovec DNA in a brain tumor biopsy from a patient in the REVERSE clinical study, a case report
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Le résumé fourni par la source
BACKGROUND: Leber Hereditary Optic Neuropathy (LHON) is a rare, maternally-inherited mitochondrial disease that primarily affects retinal ganglion cells (RGCs) and their axons in the optic nerve, leading to irreversible, bilateral severe vision loss. Lenadogene nolparvovec gene therapy was developed as a treatment for patients with vision loss from LHON caused by the most prevalent m.11778G > A mitochondrial DNA point mutation in the MT-ND4 gene. Lenadogene nolparvovec is a replication-defective recombinant adeno-associated virus vector 2 serotype 2 (AAV2/2), encoding the human wild-type MT-ND4 protein. Lenadogene nolparvovec was administered by intravitreal injection (IVT) in LHON patients harboring the m.11778G > A ND4 mutation in a clinical development program including one phase 1/2 study (REVEAL), three phase 3 pivotal studies (REVERSE, RESCUE, REFLECT), and one long-term follow-up study (RESTORE, the follow-up of REVERSE and RESCUE patients). CASE PRESENTATION: A 67-year-old woman with MT-ND4 LHON, included in the REVERSE clinical study, received a unilateral IVT of lenadogene nolparvovec in the right eye and a sham injection in the left eye in May 2016, 11.4 months and 8.8 months after vision loss in her right and left eyes, respectively. The patient had a normal brain magnetic resonance imaging with contrast at the time of diagnosis of LHON. Two years after treatment administration, BCVA had improved in both eyes. The product was well tolerated with mild and resolutive anterior chamber inflammation in the treated eye. In May 2019, the patient was diagnosed with a right temporal lobe glioblastoma, IDH-wildtype, World Health Organization grade 4, based on histological analysis of a tumor excision. The brain tumor was assessed for the presence of vector DNA by using a sensitive validated qPCR assay targeting the ND4 sequence of the vector. CONCLUSION: ND4 DNA was not detected (below 15.625 copies/μg of genomic DNA) in DNA extracted from the brain tumor, while a housekeeping gene DNA was detected at high levels. Taken together, this data shows the absence of detection of lenadogene nolparvovec in a brain tumor (glioblastoma) of a treated patient in the REVERSE clinical trial 3 years after gene therapy administration, supporting the long-term favorable safety of lenadogene nolparvovec.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Absence of lenadogene nolparvovec DNA in a brain tumor biopsy from a patient in the REVERSE clinical study, a case report
- Date Crossref
- 12/07/2022
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Emory University Departments of Ophthalmology pays non établi dans la noticeUniversité ou école supérieure
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Emory Eye Center pays non établi dans la noticeÉtablissement de santé
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Neurological Surgery pays non établi dans la noticeÉtablissement de santé
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Vanderbilt University Medical Center Department of Ophthalmology and Visual Sciences pays non établi dans la noticeÉtablissement de santé
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University of Cambridge Department of Clinical Neurosciences pays non établi dans la noticeUniversité ou école supérieure
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Moorfields Eye Hospital pays non établi dans la noticeÉtablissement de santé
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Addenbrooke's Hospital pays non établi dans la noticeÉtablissement de santé
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University College London UCL Institute of Ophthalmology pays non établi dans la noticeUniversité ou école supérieure
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MRC Mitochondrial Biology Unit pays non établi dans la noticeStructure de recherche
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Istituto delle Scienze Neurologiche di Bologna pays non établi dans la noticeStructure de recherche
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University of Bologna Unit of Neurology pays non établi dans la noticeUniversité ou école supérieure
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GenSight Biologics (France) pays non établi dans la noticeEntreprise
Departments of Ophthalmology — Emory University, Emory Eye Center et Neurological Surgery, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.