Breaking barriers to gene therapies for childhood rare diseases

November 28, 2022 - 5 minutes

The majority of known rare genetic diseases affect children, and gene therapies could help them live normal lives. Miquel Vila-Perelló, CEO and co-founder of the Spanish biotech SpliceBio, outlines how its technology could widen the range of genetic diseases treatable with gene therapies.

Last week, World Children’s Day was celebrated as a means to improve and raise awareness about children’s welfare worldwide. 

One major threat to children worldwide is the risk of developing a rare genetic disease. There are approximately 8,000 known rare diseases and — despite each condition being rare — every person has between 3.5 and 5.9 percent chance of developing one of these conditions. As 70 percent of these conditions develop during childhood, this creates large healthcare and diagnostic challenges for children around the world.

Gene therapies offer a way to provide children with rare genetic diseases a single-dose treatment for their condition. In most cases, gene therapies consist of a viral vector that carries a therapeutic gene into the patient and lets the patient produce healthy versions of a dysfunctional gene.

However, there are limits to how much genetic material a viral vector can carry. This means that gene therapies may be unable to carry large therapeutic genes, making it hard to treat some rare conditions.

Earlier this year, the gene therapy firm SpliceBio raised $57 million in the biggest Series A round in Spain’s biopharma industry. The firm aims to overcome the limited capacity of viral vectors to allow gene therapies to benefit a larger range of children with rare diseases, with a focus on the blindness condition Stargardt disease. 

Content continues below

Related Content

In an interview, SpliceBio’s CEO and co-founder, Miquel Vila-Perelló, explained how Stargardt disease can impact the lives of children and their families, and how more children can access gene therapies for these rare diseases.

Can you explain how big a problem Stargardt disease can be for young children and their families?

Stargardt disease is a genetic disease that leads to legal blindness as a result of the progressive loss of retinal cells. 

The disease can manifest at any age, but it is often in children that it manifests in its most aggressive form, progressing at an accelerated rate and resulting in legal blindness in a timeframe of a few years, sometimes even faster. 

This obviously has a devastating impact on children’s daily life and activities, including for instance their school life.

What therapies are already available for Stargardt disease, and why are gene therapies needed?

Content continues below

Related Content

Unfortunately there are no therapies approved for the treatment of Stargardt disease. A gene therapy has the potential to address the root cause of the disease and potentially stop its progression.

Many gene therapies have a limit on how much genetic material they can deliver. How does this constrain the therapy, and how can SpliceBio’s technology address this?

Gene therapy is based on the idea of delivering a correct copy of the mutated gene to the right cells to correct the disease. In the case of Stargardt, it is the ABCA4 gene in retina cells. To do that, certain vectors that can deliver this genetic material into the nucleus of cells are required. 

Adeno-associated vectors (AAV) are the most used vectors for that. However, they have a limited packaging capacity of 4.7 kilobases of genetic material. The ABCA4 gene is 6.8 kilobases long, so theoretically gene therapy with the ABCA4 gene is not possible. 

What we do is take the ABCA4 gene, split it in two halves, package each half in a separate AAV together with our protein splicing technology, and deliver the two AAVs. When the two AAVs each deliver half of the gene to retina cells, each of these genes (DNA) is transcribed (to RNA) and translated (to protein) and our protein splicing technology puts the two protein halves together to form the full-length ABCA4 protein in vivo in retina cells. 

SpliceBio raised a big funding round earlier this year. What are the company’s main milestones now that it has this cash?

The funding will allow us to take the Stargardt program into the first phase of clinical trials and build a pipeline of other gene therapy programs aimed at large genes in ophthalmology and other therapeutic areas

With a growing number of ophthalmic gene therapies nearing the market, what are the main challenges involved in ensuring access of child patients to these gene therapies?

The first step is demonstrating in clinical trials that the gene therapy is safe and efficacious. 

After that, it is fundamental that all the stakeholders involved in the evaluation, approval and access of such invaluable therapies (sponsors, patients, regulatory agencies, healthcare systems, insurers, hospitals, physicians, etc.) work together to implement the appropriate framework to ensure that patients will have access to the medicine and sponsors are incentivized to continue developing such life-changing innovations. 

A good example of such a framework is the U.S. Food and Drug Administration’s Priority Review program, which grants a voucher for priority review that expedites the review process for medicines aimed for pediatric use.

You might also be interested in the following: