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PDE6A Gene Therapy for Retinitis Pigmentosa
PDE6A geni, retinadaki çubuk hücrelerinde görev yapan bir enzimin alt birimini kodlar; bu enzimin kaybı hücre içi cGMP düzeyinin sürekli yüksek kalmasına, kalsiyum girişinin artmasına ve hücre ölüm yolaklarının aşırı etkinleşmesine yol açar. PIGMENT adlı bu Faz 1/2 (Phase 1/2) çalışmada, PDE6A ile ilişkili retinitis pigmentosa hastalarında hastalığın ilerlemesini durdurmayı ve görme işlevindeki bozulmayı engellemeyi hedefleyen rekombinant adeno-ilişkili viral (AAV) vektör rAAV.hPDE6A, tek seferlik retina altı (subretinal) enjeksiyon olarak uygulanmaktadır. Katılım için retinitis pigmentosa tanısı, doğrulanmış PDE6A gen mutasyonu, 18 yaş ve üzeri olmak ve görme keskinliğinin en az 20/400 olması gerekmektedir.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Inclusion Criteria: * clinical diagnosis of retinitis pigmentosa * confirmed mutation in PDE6A gene * ≥ 18 years of age * visual acuity ≥ 20/400 * no infection with Human Immundeficiency Virus (HIV) * negative pregnancy test in women with childbearing potential (a woman who is two years post-menopausal or surgically sterile is not considered to be of childbearing potential) * Male patients must agree to use condoms during the first 6 months post treatment. * Female patients of childbearing potential must agree to use an effective method of birth control during the first 6 months post treatment. * ability to understand and willingness to consent to study protocol Exclusion Criteria: Ocular (study eye \& fellow eye) * additional interfering ocular conditions with impact on study results (e.g. ocular opacity and advanced cataract, uveitis, amblyopia) * recent (6 months) ocular surgery, intravitreal or subretinal implantation of a medical device * disease causing mutations in another known retinitis pigmentosa gene * ocular infection with herpes simplex virus in medical history * history of ocular malignancies * disorders of the internal retina (e.g. retinal detachment in the patients history) * glaucoma defined as damage of the optic nerve * vascular retinal occlusion * diabetic patients suffering from retinopathy and/or macula edema * any other retinopathy due to other diseases e.g. (but not limited to) arterial hypertension, trauma or acquired inflammatory diseases (uveitis serology), contraindication to pharmacological mydriasis (e.g. history of angle block glaucoma) * absence of visual function on the contralateral eye Systemic * systemic conditions (e.g. coronary heart disease, autoimmune disorders) which may affect study participation or outcome measures * History of poorly controlled Diabetes Mellitus type 1 or type 2 * systemic illness or medically relevant abnormal laboratory values in blood analysis including renal and hepatic functions at inclusion * patients treated with oral corticoids within 14 days prior inclusion * current or recent participation in other study/or administration of biologic agent within the last three months * known sensitivity to any compound used in the study * contraindications to systemic immunosuppression * contraindications in view of the planned surgery (e.g. but not limited to anaemia Hb\<10g/dl, coagulopathy with PT/PTT \>1,5 fold upper limit, hypertension with values above 180 mmHg systolic and 110 mmHg diastolic) including intolerance and contraindications to general anaesthesia * intolerance to contrast agents used for diagnostic methods like angiography with fluoresceine or indocyanine green (e.g. but not limited to hyperthyroidism, hepatic insufficiency) * subject/partner of childbearing potential unwilling to use adequate contraception for four months * nursing or pregnant women * any other cause that, in the investigator's opinion, renders potential subjects not suitable for the study