Creation and spinout of Nightstar, a retinal gene therapy company

Most incurable forms of blindness are due to genetic diseases caused by faulty genes in the cells in the light-sensitive region of the eye, known as the retina. These defective genes eventually lead to the dysfunction and death of the affected cells. The progressive death of these cells causes a gradual degeneration of the retina, resulting in sight loss and ultimately blindness.

Professor Robert MacLarenProfessor Robert MacLaren
Until now, genetic eye diseases have been incurable. However, a new technique called gene therapy may help to slow or even stop the degeneration. This technique involves putting normal copies of the affected gene back into the cells of the retina to help them to function normally. This is achieved by using a harmless virus known as adeno-associated virus, or AAV, to carry normal genes into the retinal cells. In 2009, the team commenced the development of AAV gene therapies for treatment of choroideremia and X-linked retinitis pigmentosa (RP), incurable genetic diseases that cause blindness in men. Sight loss in choroideremia and X-linked RP begins with ‘night blindness’ in adolescence, followed by a gradual loss of peripheral vision which results in progressively worsening ‘tunnel vision’, and ultimately complete blindness.

The promising results from their initial research enabled the team to commence a Phase 1/2 clinical trial in 2011 to test their AAV gene therapy for choroideremia. Following the positive outcomes observed in many of the choroideremia patients following treatment with the gene therapy, a gene therapy company (Nightstar) was spun out of their research programme in 2014 to expedite clinical evaluation of the choroideremia gene therapy and advance multiple gene therapies for inherited retinal disorders (all developed in the MacLaren laboratory) into human clinical trials. This enabled the team to commence a Phase 1/2 clinical trial in 2017 to test their AAV gene therapy for X-linked RP, followed by an international Phase 3 clinical trial of their choroideremia gene therapy in 2018.

On the back of this progress, Nightstar was acquired by Biogen for $877 million in early 2019 – just five years after its founding. The deal ranks as the third most valuable British biotech exit in the last two decades.

Funded by: National Institute for Health Research, Wellcome Trust, Medical Research Council and Nightstar Therapeutics