The Potential of Optogenetics

More than a decade ago, I had learned about an exciting new research technique called optogenetics. Back then, it was (and still is) largely considered a research tool. In essence, it’s a new(ish) way of activating genes with light. More specifically and importantly, it has the potential to regulate specific neurons. From a research standpoint, this is really useful; however, it has the potential to become a new therapeutic modality, maybe.

Current tools for treating mental and behavioral disorders can be difficult to prescribe and manage. Many drugs exist to treat disorders such as depression, anxiety, Schizophrenia, etc, but often leave a lot to be desired – side effects, non-responders to certain medications and tolerance are all known issues.

Many CNS drugs hit many different receptors in the brain at varying levels of specificity, and tremendous complexity. Other interventions, like transcranial magnetic stimulation or deep brain stimulation, are marginally and/or temporarily effective but are entirely non-specific.

Because optogenetic approaches are capable of regulating specific clusters of neurons, it really does open up a new world of possibilies.

2021 Albert Lasker Basic Medical Research Award

You may know have heard of the Lasker Award but if not, it’s kind of like getting selected #1 in the NFL draft. In that last 20 years, 32 Lasker Awardees have become Nobel laureates. Not a guarantee, but a pretty good bet.

Karl Deisseroth (Stanford), Peter Hegemann (Humboldt University of Berlin) and Dieter Oesterhelt (Max Planck Institute) were collectively honored with the 2021 award for “Light-sensitive microbial proteins and optogenetics.” Karl Deisseroth’s lab made a big contribution in 2007, where they demonstrated you could command the behavior in rats using a gene delivery system, light-sensitive gene and optical probe (see below). This is just one example of research that has demonstrated it’s potential.

But wait, it gets even better.

Translating Optogentics

Last year, Deisseroth’s group published a report demonstrating they could do this non-invasively (admittedly only up to 7mm), without the need for the intracranial probe seen above (Chen et al. (2021)). This is more feasible in mice, due to their relative size; but does demonstrate working toward a significant challenge in this type of phototherapy (that is, light penetration limitations). A challenge, but given it’s potential could be overcome in humans with things like interventional radiology devices (i.e. light-delivering catheter). Snake a catheter through a blood vessel to your area of interest, then shine.

A group in Germany demonstrated the use of optogenetics in a blind patient with Retinitis pigmentosa, a rare disorder where rod photoreceptors are lost, leading to blindness. In this work, the group demonstrated they could partially restore vision by activating optogenetically transduced retinal cells (Sahel et al. (2021)).

I’m very interested in seeing more work on this, and am cautiously optimistic. The field has come a long way and hopefully more work will demonstrate optogenetic’s potential as a therapy.

References