A phase 1/2 study involving antisense oligonucleotide therapy to correct splicing in centrosomal protein 290, a cause of Leber congenital amaurosis, showed significant vision improvement in 3 months, according to the study published in Nature Medicine.
“LCA10 [Leber congenital amaurosis 10] is a severe form of childhood blindness, and this is a major step forward in the treatment of these previously incurable conditions,” co-investigator Samuel G. Jacobson, MD, PhD, Scheie Eye Institute, said in a press release about the study.
Ten patients with Leber congenital amaurosis (LCA10) were treated with intravitreal injections of an antisense oligonucleotide to restore correct splicing, an issue caused by patients carrying the c.2991+1655A>G allele leading to centrosomal protein 290 (CEP290) mutations. According to the study, most LCA10 patients would lose all rod photoreceptors except for a central island of some poorly functioning.
Each subject received no more than four intravitreal injections. Patients in the study group presented with a baseline visual acuity of 1.1 log10 MAR to light perception, and the contralateral untreated eyes had baseline acuity of 0.7 log10 MAR to light perception.
Cideciyan and colleagues found that at 3 months after initial injections, one patient presented a large, 2.7 log10 MAR, improvement, while four others showed a clinically meaningful 0.3 log10 MAR improvement.
At 3 months, participants received a second injection. A comparison at baseline showed that treated eyes were 0.12 log10 MAR, or six letters, worse than the patients’ contralateral untreated eyes, according to the study. After intravitreal antisense oligonucleotide injections, interocular asymmetry reversed, and treated eyes showed a 0.54 log10 MAR, 26-letter, improvement over untreated eyes.
“It was enormously gratifying to see robust improvements in visual acuity and significant augmentations in the patient’s ability to detect lights and impressive to observe these effects within the first 3 months following a single injection,” co-investigator Artur V. Cideciyan, PhD, said in the press release.
Cideciyan and colleagues noted that there are still many questions regarding the longevity of this treatment as well as the safety of further dosages, but this study represents a large step in therapeutic opportunities. – by Scott Buzby
Disclosures: Cideciyan and Jacobsen report no relevant financial disclosures. The work was supported by clinical trial contracts from ProQR Therapeutics to the principal investigators. Please see full study for all other authors’ disclosures.