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Clinical trial research for gene therapy for CNGA3-linked achromatopsia has reported on safety and vision outcomes.

Clinical researchers at the University Hospital Tuebingen has published a report on an AAV-CNGA3 gene therapy treatment among 9 patients.  The results of the clinical research had no substantial safety problems and was associated with cone photoreceptor activation in adult patients, based on the basis of visual acuity and contrast sensitivity gains.  The study provides a clinical proof-of-concept result using gene supplementation for photopic vision caused by pathogenic variants in the cone photoreceptor-specific gene CNGA3.


Achromatopsia (ACHM) is a rare disorder with an estimated prevalence of 1:30,000 to 40,000, characterized by reduced central visual acuity (<20/200), pendular nystagmus, photophobia, eccentric fixation and reduced or complete lack of colour discrimination.  The disorder is an autosomal recessive condition caused by mutations in one of six genes: CNGB3, CNGA3, GNAT2, PDE6C, PDE6H and ATF6.  CNGA3 and CNGB3 (the cone-specification channel cyclic nucleotide gated channel α and β 3) are estimated to account 75-80% of all cases. The diagnosis is made on electrophysiology (ERG) where cone cell function is absent, while in contrast, rod function is normal. The disease is essentially stable. The glare and photophobia can be ameliorated with either a brown or red tint in glasses and currently there is no treatment.


The current trial was an open-label, exploratory non-randomized controlled trial testing safety and vision outcomes of gene therapy using a vector AAV8.CNGA3.   Nine patients had an age range between 24-59 years, 8 male and 1 female. Baseline visual acuity letter score ranged from 34 (20/200) to 49 (20/100), whereas baseline contrast sensitivity log scores ranged from 0.1 to 0.9. The mean change in visual acuity of 2.9 letters (95%CI, 1.65-4.13; P=0.006). Contrast sensitivity improved by a mean of 0.33 log (95%CI, 0.14-0.51 log; P = .003).  This current study compares with a previous interim result (January, 2020) from a commercial company, ACGT plc., Florida, posted results earlier of the year indicating preliminary outcomes for 22 patients – 9 patients for AAV-CNGA3 and 13 patients for AAV-CNGB3.  In the CNGA3 study, 9 patients had a VA letter change ranging from 2-4 letters (across 3 doses), while In the CNGB3 study, 13 patients had a VA letter change ranging from 1-3 letters.  Clearly, there appears to be some consistency in the independent VA outcomes (i.e., University of Tuebingen vs. AGTC Inc., Florida).  Commenting on the report from the Tuebingen study, the researchers stated, “future studies are needed to investigate whether treatment at an earlier age (i.e., before closure of the critical period of visual cortex development at the age of approximately 7-8 years and before structural loss of cone photoreceptors) will lead to greater functional benefit because of higher cortical plasticity”.