Optogenetic therapy lets blind person see

Worldwide first RP gene therapy

In December 2017, the U.S. FDA approved the first gene therapy for a hereditary eye disease that can lead to blindness as early as age of 20. LUXTURNA (Voretigene neparvovec) was developed by the U.S. biotech company Spark Therapeutics, founded in 2013. Approval in Europe by the EMA (European Medicines Agency) followed in 2018. Novartis from Switzerland secured global marketing rights - with the exception of the U.S.

Mode of action of Luxturna

Mode of action of Luxturna

In December 2019, Roche, also based in Switzerland, paid $4.3 billion to acquire Spark, which will remain an independent subsidiary.
LUXTURNA uses as its gene delivery vehicle a virus that provides retinal cells with a functional copy from the RPE65 gene. The RPE65 protein encoded by this is a visual pigment missing in the disease.  With a price tag of $850,000, the therapy is one of the most expensive on the U.S. market.

What is optogenetics and how does it treat blind people?

Optogenetics is basically about introducing genetic information into target cells that codes for light-sensitive ion channels, transporters or enzymes. Ultimately, cellular activities can be controlled with light.

The starting point was research by Peter Hegemann's team at the Humboldt University in Berlin, which studied the green alga Chlamydomonas in the 1990s and discovered so-called channel rhodopsins. These proteins act like switches in certain cells that react to light. 

In 2004, Karl Deisseroth's team at Stanford University succeeded in inserting the gene of these algal proteins into the nerve cells of a mouse. They then produced the protein and became light-sensitive. This made it possible to control the mouse remotely by light impulses: it ran around in circles, stopped and started running again.

Since then, Deisseroth has been regarded as the founder of optogenetics, i.e. the control of genetically modified cells with the aid of light. The technique was named Method of the Year 2010 by Nature Methods.

By means of a fiber optic cable inserted into the brain, nerve cells can be activated or deactivated in a mouse experiment. Image source: KlarText

New gene therapy makes a blind person's retina sensitive to light, aided by light-stimulating goggles that use a neuromorphic camera to capture images from the visual world. Image source: GEO

For the therapy of blind patients, optogenetics offers the advantage that it can be used independently of mutations. This is because new light-sensitive molecules are introduced into the eye and no attempt is made to replace non-functioning ones by gene transfer.
In the study, the team injected a single dose of viruses into the man's more severely affected eye, which transferred the blueprint for the light-sensitive protein derived from microalgae (canal rhodopsin). This forms an ion channel in certain cells of the lower retina. This is needed to generate electrical signals from incident light, which the cells transmit to the visual center in the brain. Since daylight is not sufficient to activate the ion channel, camera glasses assist by projecting images of the surroundings through the pupil onto the retina in real time at a very high intensity.