Gene therapy shows promise in glaucoma research

Key Takeaways

• Researchers have discovered that deficiency of an enzyme called NMNAT2 renders the nerve cells of the eye vulnerable to neurodegeneration.
• Increasing NMNAT2 levels in rodent models of glaucoma through gene therapy protected the nerve cells. 

In the 1980s, research into neurodegenerative diseases discovered a link between glaucoma and NAD, a type of molecule called a co-enzyme that binds to an enzyme and makes it active. Researchers showed that NAD levels were low in animal models of glaucoma. 

It was also found that when the body makes NAD, it uses an enzyme called NMNAT1. However, in neurons, it needs another enzyme: NMNAT2 (which is only found in neurons).

Pete Williams, who led the early research on NAD and glaucoma, is the senior author of a new paper in Nature Communications on how deficiency of the enzyme NMNAT2 renders the nerve cells of the eye vulnerable to neurodegeneration, which could be key in the search for a treatment for glaucoma. “In our recent paper in Nature Communications, we show that NMNAT2 is needed to protect neurons in the eye and that gene therapy can be used to increase levels,” says Williams. 

While this research was conducted in rodent models, the researchers are hopeful that NMNAT2 may be an important new therapeutic target for people with glaucoma. To this end, the research team is now moving on to try to develop new substances that target NMNAT2 in nerve cells. “We believe these compounds could be a starting point for future glaucoma treatment,” Williams adds.

Edited by Miriam Kaplan, PhD

Sources:

Karolinska Institutet, Medical Xpress, August 7, 2024;  source article

James R. Tribble et al, “NMNAT2 is a druggable target to drive neuronal NAD production”, Nature Communications (2024). DOI: 10.1038/s41467-024-50354-5