‘Give Us Hope’: Bringing Together Leber Congenital Amaurosis Researchers and Patients

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Promising gene therapy research – characterized as having a good potential to restore vision – is underway to help visual impairment caused by a form of Leber congenital amaurosis (LCA) attributable to a mutation in the IQCB1 gene.

Amy Laster, PhD, Vice President of Science and Awards Programs for the Foundation Fighting Blindness, shared the research news as part of a recent LCA Research Update webinar summarizing results of an IQCB1/NPHP5-associated retinal disease Scientific Advancement Workshop conducted a week earlier.

Laura Manfre, Sofia Sees Hope Co-Founder and President, said more than 40 leading experts in ophthalmology and gene research gathered for the virtual workshop to share research and patient perspectives and identify the next steps to advance treatment for the patient community. Sofia Sees Hope and the Foundation Fighting Blindness hosted these Scientific Advancement Workshop to widen the circle of research awareness, build a framework or platform for sharing knowledge, foster collaboration among stakeholders, identify gaps, and set priorities for action. The format was based on a similar program run earlier for the RDH12 gene.

“Our objective today is to engage you and our IQCB1/NPHP5 community to seek to advance treatment for ourselves and our loved ones…” Manfre said in her introduction. 

“There are no easy answers and there are no quick or fast solutions; just wanted to set that expectation up front even as we are very excited to share the news that we have for you.”

Early-stage translational research

The reported results are from early-stage translational research, which involves moving discoveries from basic science and animal models to applying them in human clinical trials.

The news comes after a successful proof of concept or feasibility study by Dr. Gustavo D. Aguirre, VMD, PhD. He is Professor of Medical Genetics and Ophthalmology at the School of Veterinary Medicine, University of Pennsylvania, and he identifies dogs with inherited eye and retinal degeneration. 

Dr. Aguirre will be presenting results of his proof of concept gene therapy study on LCA-NPHP5 dogs in a paper soon to be published in a peer-reviewed journal. The research is detailed in bioRxiv (pronounced bio-archive), a repository for preprinting papers prior to publication. 

Laster said the study showed that photoreceptors in treated areas had structural improvements and the dogs had improved visual function. 

Researchers sent dogs through an obstacle course under dim light and under bright light. Navigating with their treated eye, the dogs had faster travel times and fewer collisions than when they navigated using their untreated eye.

She called the findings very promising, saying, “We’re excited about these results.”

Laster also cited ongoing clinical studies suggesting that the structure of the central retina or macula is preserved for many years despite having significant loss of vision.

“This, if you will, dissociation between the structure and function suggests that a gene therapy targeted at the central retina not only could work but has a good potential to restore lost vision,” she said. “So we build on this proof of concept and clinical knowledge toward translating these laboratory-based research concepts into clinical trials for patients.”

Next steps

The next steps include designing clinical trials and identifying relevant endpoints and outcomes to measure the safety and effectiveness of the gene therapy.

Webinar speaker Todd Durham, PhD, Vice President of Clinical and Outcomes Research at the Foundation, said the dog model studies began about four years ago. He said it is unknown when clinical trials would begin because more work needs to be done prior to launching them. Durham emphasized the importance of the research results, saying, “They’ve very much ticked off a major milestone in this proof of concept canine model.” 

Scientific workshop participants also learned that Dr. Aguirre and his colleague, Dr. William A. Beltran, DVM, PhD, co-founded a Philadelphia-based biotechnology company called LuxFiat Therapeutics. 

Laster said this would position the scientists to advance the gene therapy into clinical trials and said that the Foundation will continue to do all that it can to accelerate any clinical development.

The Foundation, the largest private funder of research for treatments and cures of blinding retinal diseases, has raised nearly $800 million since its inception and currently funds more than 80 research projects globally. Dr. Laster oversees the Foundation’s preclinical research portfolio consisting of research awards in funding programs that support career development, laboratory-based science research, translational research, and multi-investigator program projects.

In the question-and-answer session, Durham discussed a query from the audience as to whether it was unusual to receive an incorrect diagnosis of retinitis pigmentosa (RP) before later getting a confirmed genetic diagnosis of Leber congenital amaurosis from Spark Therapeutics. 

Durham said it was not unusual and that it was great the audience member got a genetic diagnosis.

“The clinical manifestations of what many ophthalmologists observe when they do an exam can overlap quite a bit from various conditions,” he said. “Ultimately, at the end of the day, the fact that you got a genetic diagnosis is most informative for you, and that’s our hope that there will be more access to genetic testing. Just to reassure you, I don’t think your story is very unusual at all, unfortunately, but hopefully access to genetic testing going forward is going to make that a less frequent story.”

Supporting the Leber congenital amaurosis community

Manfre, responding to a question about help specifically for those with the IQCB1/NPHP5 mutation, said Sofia Sees Hope supports the entire Leber congenital amaurosis community and suggested looking at the website’s Resources page and joining a highly active IQCB1/NPHP5 Facebook group that she joined because her daughter Sofia has the same genetic variant.

Durham also devoted the beginning of the webinar delivering preliminary information from an ongoing patient survey on perspectives of people affected by LCA or RP and their caregivers.  

He said the survey results will be available to the community after final analysis of the data. 

Here are the topics addressed in the survey developed by Sofia Sees Hope and the Foundation:

  • Diagnostic Journey
  • Current Best Corrected Visual Acuity
  • Visual Symptoms
  • Other Related Conditions
  • Worries
  • Impact on Your Family Overall
  • Participating in Clinical Trials
  • Motivations for Participating in a Clinical Trial
  • Anything Else to Share with Researchers.

Under the last topic, a participant responded: “Time is vision. Please hurry for IQCB1. Give us hope.”

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