Trinity professor eyes the future of gene therapy

10 May 2016

Prof Jane Farrar and her colleagues have developed a gene-based technology to tackle an inherited form of degenerative blindness.

When you make a biomedical discovery in the lab, you hope that some day it will help people. For Prof Jane Farrar and colleagues, that day got a bit closer in March this year when Trinity College Dublin spinout company Genable Technologies was acquired by US-based Spark Therapeutics.

The acquisition marks the latest step in a scientific story spanning decades, and next week (17 May) Farrar will speak about the importance of industry-academic collaboration in bringing important discoveries to the clinic.

Gene-ius insights

It all started in Trinity when Farrar was a PhD researcher, looking at the genetics in an inherited form of blindness called retinitis pigmentosa (RP), where the light-sensitive retina at the back of the eye breaks down and can no longer function. The result is that the person gradually loses their sight.

Funded by the patient organisation Fighting Blindness, Farrar worked with Prof Pete Humphries and ophthalmologist Prof Paul Kenna. In the late 1980s and early 1990s, they analysed genes from a large Irish family and they identified important mutations in the rhodopsin gene that were linked to the degenerative disease.

The team was interested in how gene therapy might be used to restore the function of the faulty genetics, but there was a catch: this particular gene is ‘dominant’, and inserting a working version of the gene into the eye might not be enough to stop the degenerative damage caused by the mutant gene.

“There are very specific problems in treating dominant forms of disease,” explained Farrar. “It’s not a case of delivering the normal gene and there is your therapeutic strategy – you may need to suppress the mutant gene and encoded protein, and we thought about ways we could do that.”

There was an added complication that RP is not caused by the same mutation in everyone – an individual could have one of hundreds of mutations. “Targeting each of these mutations would not be economically or even technically very feasible,” she said.

So, the Trinity researchers (including Farrar, Dr Sophia Millington-Ward, Dr Apad Palfi and Dr Naomi Chadderton) devised and tested a gene-therapy approach to suppress mutant gene activity while also introducing a working version into the eye that would not be suppressed.

“We patented that technology and brought it forward, spinning that out into Genable Technologies,” explained Farrar, who was a co-founder and the chief scientific officer of the spinout company.

Bright sparks

In March this year, it was announced that Spark Therapeutics was acquiring Genable.

“They are absolutely the right team to take this forward,” said Farrar. “Spark is a global leader in the field of gene therapy and has the many diverse skills needed to drive this therapy forward.”

Meanwhile, Farrar and colleagues are continuing to forge ahead with research on many fronts – some of the team are just back from the ARVO vision science conference in Seattle, where they presented findings on next-generation sequencing of samples from Irish families with inherited blindness.

Knowing the ‘genotype’ or specific genetic changes associated with an individual’s blindness is important, not only to provide a clear diagnosis for patients, but it also means that those individuals can, in principle, be identified as suitable to take part in future studies, Farrar explained. “If we want patients to have the opportunity to be able to partake in future clinical trials, it is essential to know what the genotype of each patient is.”

Computational biology and bioinformatics have become extremely important for the field of eye genetics, as they have for many areas of biomedical science, she added. “We need people who can analyse datasets in an efficient and effective way.”

Let the baby grow

Farrar is one of several researchers from Trinity and the Royal College of Surgeons in Ireland who will be speaking at the upcoming Biomedical and Life Sciences Innovation Showcase at Science Gallery Dublin on 17 May. Trinity and RCSI are consortium partners under Enterprise Ireland’s Technology Transfer Strengthening Initiative Phase 2.

So, how does she feel, now that the RP gene discovery is moving on to a new phase with Spark?

“People ask me was it hard to let go of your baby, and I say not really – what happens to it otherwise?” said Farrar. “We need people with the right skillsets and sufficient resources to fund the trials that are needed to bring this towards the clinic.”

The Trinity researcher, whose work has been supported by Science Foundation Ireland, the Health Research Board, Wellcome Trust, EU Framework programmes, Fighting Blindness Ireland and Foundation Fighting Blindness US, has seen the support systems in Ireland improve for knowledge transfer – and she encourages other researchers to embrace the process.

“A technology will only really move forward to the market if it is commercially attractive, and how you empower a discovery is to protect it with IP and make it commercially interesting to a third party that is prepared to put sufficient people and financial resources in it to drive it forward.”

You can register for the free Biomedical and Life Sciences Innovation Showcase here.

Dr Claire O’Connell is a scientist-turned-writer with a PhD in cell biology and a master’s in science communication