Case Study: Drug Discovery

Eye research with ripple effects across medicine

Dr. Yang Hu and his lab are  developing drugs and gene therapies to delay or stop degeneration in the optic nerve.

DEVELOPMENT is always a long and rigorous process, but it is also a critically important challenge.

Facilitated by the Mary M. and Sash A. Spencer Center for Vision Research at the Byers Eye Institute at Stanford, more than 150 researchers—including faculty, postdoctoral scholars, graduate students, laboratory staff, residents, fellows, visiting researchers, and undergraduates—log hundreds of thousands of hours a year in our laboratories to advance the science that may ultimately lead to new and innovative discoveries and treatments for vision-stealing diseases.

Today, dozens of potential new treatments for a long list of eye-related diseases are in development by Byers Eye Institute faculty and researchers. Many of these are even making strides on the path toward FDA approval.

“Developing new treatments is a priority for us at the Byers Eye Institute as we continue to push ourselves to translate research from the lab into the clinic to benefit patients,” said Jeffrey Goldberg, MD, PhD, Blumenkranz Smead professor and chair of ophthalmology.

Among the faculty and researchers working toward that end is Yang Hu, MD, PhD, associate professor of ophthalmology.

Hu and his team are working toward a new way to treat glaucoma, an optic nerve disease that affects more than 3 million Americans a year.

Glaucoma, which causes gradual vision loss, is the leading cause of irreversible blindness worldwide. The disease is the result of retinal ganglion cells (RGCs) and their axons in the eye becoming damaged.

Today, the only treatment for glaucoma is to lower the pressure in the eye, called intraocular pressure (IOP), with eye drops, laser procedures, oral medications, surgery, or a combination of those. But even with all of those options, doctors still can’t prevent vision loss or restore eyesight in glaucoma patients, Hu says.

“That there is no curative neuroprotective or restorative therapy for neurodegeneration is a central challenge for human health,” he lamented in a recent interview.

Hu’s team is pursuing the prevention of glaucoma effects via new drugs and gene therapies that could delay or stop the degeneration of the optic nerve, the retinal ganglion cells, and their axons, independent of the pressure in the eye, and even regenerate the optic nerve to restore vision.

An elusive target

Discoveries in this area would break new ground. Scientists have long sought therapies to protect or regenerate cells in patients with degenerative diseases of the central nervous system, like glaucoma, with little luck.

To reach their goal, Hu and his team are focusing on the underlying causes that drive neuronal degeneration and axon regeneration after injury or disease, and they’ve made remarkable recent strides. So far, Hu’s team has shown proof of concept for their treatments in animals, which signals the potential to also work in humans.

Now the work is progressing in preclinical studies, in which the team tests both safety and effectiveness in larger lab animals with eyes more like human patients.

Discoveries in Hu’s lab provide a prime example of how progress at the Byers Eye Institute is capturing the interest of Stanford supporters, and international funders.

This year, Hu received support from Stanford’s Innovative Medicines Accelerator (IMA), and SPARK at Stanford, both programs designed to eliminate obstacles and speed the translation of Stanford’s research discoveries into new treatments for patients.

The IMA and SPARK, Hu says, can provide the specialized expertise to help advance the work into clinical trials and provide funding to widen testing.

Hu’s work has also been recognized beyond the Stanford campus. In June, he received the prestigious national Research to Prevent Blindness Stein Innovation Award, which will provide flexible research funding to support his team’s work in related research.

Beyond glaucoma

Hu’s discoveries could also have implications beyond glaucoma to other degenerative eye and even brain diseases, including Alzheimer’s, Parkinson’s Disease, and ALS (amyotrophic lateral sclerosis).

“We are targeting glaucoma first,” he said. “But if we can develop a neuroprotective treatment that shows effectiveness in glaucoma, it could very well be applicable to other neurodegenerative diseases.”

Marcia is a freelance writer for the Byers Eye Institute at Stanford.