A gene therapy operation in progress.

Translating science into the world of business

Making scientific breakthroughs can be challenging enough, but translating results into real-life medical treatments can present additional hurdles. Professor Robert MacLaren of Oxford University’s Nuffield Department of Clinical Neurosciences is no stranger to any of these obstacles.

Oxford University
Aug 28 · 6 min read

When Professor MacLaren first wrote a grant application to the Wellcome Trust to trial retinal gene therapy in mice in 1999, the reviewers commented that it was impossible and would never work. Just 20 years later in March 2019, Nightstar Therapeutics — the company set up to develop his research — was sold for $877 million (£663 million) to the Swiss company Biogen.

According to Alex Ralph, Business Correspondent to the Times newspaper, this represented the biggest exit for a UK biotech company of the decade and ranked within the top three of all time. This underscores the huge potential of gene therapy as a new means of treating disease.

It began in 2011 at the Oxford Eye Hospital, when 14 patients took part in the world’s first gene therapy trial for a genetically caused type of blindness known as choroideremia. Each of the patients received a single injection into the back of the eye of a specially engineered virus containing a gene that cells in their eyes were missing. Five years later, the 12 patients in whom the surgery had occurred without complications had either improved or maintained vision.

(left) Yellow retina seen in choroideremia and (right) gene therapy surgery.

The trial was led by ophthalmologist Professor MacLaren, who has been working on gene therapy since he was a DPhil student in Oxford more than 20 years ago.

The idea of gene therapy is to alter or correct inherited diseases at the level of the DNA, and if successful a single treatment might have life-long effects. These early results appear to show that a single gene correction can have long-lasting beneficial effects on nerve cells of the retina to prevent blindness.

‘We are harnessing the power of the virus, a naturally occurring organism, to deliver the DNA into the patient’s cells,’ explains Professor MacLaren. ‘When the virus opens up inside the retinal cell it releases the DNA of the gene we have cloned, and the cell uses this DNA to make a protein that we think can modify the disease.

‘The development of genetic treatments for conditions like this, which would be administered early on to preserve vision in patients who would otherwise lose their sight, would be a tremendous breakthrough in ophthalmology and are something I hope to see in the near future.’

Retinal sensitivity map in a patient with choroideremia.

The leap from the lab to the ward

Taking research from the laboratory into hospitals is a big step when developing new treatments, and there can be a number of challenges — particularly the issue of finance.

Raising the funding to develop successful research into treatments in clinical trials usually involves taking on board investors, and the way many researchers do this is to form a spinout company.

Professor MacLaren originally approached the University’s research commercialisation arm, Oxford University Innovation (OUI), back in 2009 when it was called Isis Innovation.

‘The Isis Innovation technology transfer manager helped me with the original IP, which we needed for the clinical trial funding agreement,’ he explains. ‘This was my first experience of filing patents, securing any translational funding or working with a technology transfer office.

‘He helped me to understand the IP issues around the vector and introduced me to the team at the investment company, Syncona, who were keen to fund the follow-on work for choroideremia.’

In 2014, with the help and support of OUI, Professor MacLaren officially co-founded the private biotechnology company Nightstar Therapeutics with Oxford University, to develop commercial gene therapy treatments to treat choroideremia, which affects 1 in 50,000, and other forms of inherited retinal dystrophy.

The spinout company was initially backed by investment from Syncona LLP, the Wellcome Trust venture capital fund, and Oxford Spin-out Equity Management. Further investment followed over the proceeding years from other investors including NEA, Redmile and Wellington Partners before the company floated on the Nasdaq stock exchange in 2017.

During this time the Oxford trial has led to a much larger international gene therapy trial involving over 100 patients across nine countries in the EU and North America. Nightstar Therapeutics is now leading the development of this potential treatment for choroideremia, as well as a number of gene therapies for other eye diseases.

Through its equity realisation on the 2019 sale of the company, the University of Oxford received a total of £18.4 million resulting from the sale of its founding shareholding — money that will be available to continue investing in other promising future research and innovation support.

Despite this enormous commercial success, Professor MacLaren is far from slowing down, and is still exploring new applications for his gene therapy. In February 2019, Janet Osborne from Oxford became the first person in the world to undergo an operation to prevent age-related macular degeneration (AMD) — the UK’s most common cause of blindness, affecting more than 600,000 people nationally.

‘This is a rapidly evolving field,’ Professor MacLaren adds. ‘Given that we understand a lot more now about the manufacture of the viral vector, and the effects of the virus when applying gene therapy at the back of the eye, as well as all the other gene therapy programmes being developed at the moment, I would hope that we’ll see a treatment for people with dry AMD within the next few years.’

Lessons learned

Nightstar’s products are probably one of the best examples of how gene therapy can benefit humans, and they are already making a big difference in people’s lives.

Looking back on his experience, Professor MacLaren has no doubt that despite the challenges, paperwork and long hours, it has been worth it. ‘I have hundreds of patients in my clinic who are going blind but for whom we could inject a potential gene therapy cure available upstairs in our lab,’ he says. ‘The route from laboratory to clinic is long, but meeting these patients every week provides a tremendous incentive for me.’

There were practical lessons that Professor MacLaren learned along the way that may seem simple but which any researcher should consider from as early a stage as possible. During the process, his team moved all of the laboratory’s data to an electronic record-keeping system, which enabled them to generate information for regulatory authorities far more quickly and efficiently. Most importantly, no commercially valuable research data was divulged in any form, until the IP had been filed by OUI. Even members of his own department were excluded from certain lab meetings in which sensitive information was being discussed.

For others who would follow in his steps, his advice is clear: ‘Don’t get too distracted by people who tell you that you can’t do something. Listen to the people that tell you what you can do.’


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Oxford University

Oxford is one of the oldest universities in the world. We aim to lead the world in research and education. Contact: digicomms@admin.ox.ac.uk

Oxford University

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Oxford is one of the oldest universities in the world. We aim to lead the world in research and education. Contact: digicomms@admin.ox.ac.uk

Oxford University

Oxford is one of the oldest universities in the world. We aim to lead the world in research and education. Contact: digicomms@admin.ox.ac.uk

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