New Hope for Leber Congenital Amaurosis Patients: Oral Retinoid Trial Shows Promising Results

For individuals and families navigating the challenges of inherited retinal diseases (IRDs), particularly Leber congenital amaurosis (LCA), news of potential new treatments offers a beacon of hope. A recent open-label phase 1b trial, published in The Lancet, investigated an oral 9-cis retinoid (QLT091001) for childhood blindness caused by RPE65 or LRAT gene mutations, showing encouraging results for improving visual function.

Leber congenital amaurosis (LCA) is a severe form of inherited retinal degeneration that leads to blindness, often from birth or early childhood. It is caused by mutations in more than a dozen genes, with RPE65 and LRAT being among them. These mutations disrupt the retinoid cycle, a crucial process that produces 11-cis retinal, a molecule essential for capturing light and initiating vision. Without it, retinal cells cannot create vision and may eventually die.

Key Findings from the Phase 1b Trial

The trial, conducted at McGill University's Montreal Children's Hospital, enrolled 14 patients aged 6 to 38 years with LCA due to RPE65 or LRAT mutations. Participants received oral QLT091001 (synthetic 9-cis-retinyl acetate) daily for seven days. The study aimed to assess the replacement of the missing chromophore 11-cis retinal.

According to the findings, the oral therapy was generally well-tolerated. While some transient side effects were noted, such as headaches (11 patients) and photophobia (11 patients), no serious adverse events occurred. Importantly, the trial reported improvements in visual function for a significant number of participants:

  • Visual Field Improvement: Ten out of 14 patients (71%) showed an improvement in Goldmann visual field (GVF) areas, with a mean increase in retinal area ranging from 28% to 683%.
  • Visual Acuity Improvement: Six out of 14 patients (43%) experienced an improvement in visual acuity, with a mean increase of 2 to 30 letters.
  • Sustained Response: For some patients, these improvements were sustained. Two years after the trial, three patients still had a sustained GVF response, and four had a sustained visual acuity response.

Researchers noted that this oral drug appeared to