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Mass Eye and Ear Scientist Identifies Molecule Unlocking Glaucoma

8 minute read

Potential cure may impact other neurodegenerative disease therapies

There is no cure (yet).

Glaucoma often robs patients of sight as fluid in the eye builds up and increases pressure on the optic nerve. This group of diseases is so common that in the United States, more than 3 million people will receive the crushing diagnosis, 80 million globally. Glaucoma remains the second leading cause of blindness worldwide.

Eye drops, pills, or laser surgery can manage the disease when detected early, but, like many diseases, symptoms are not always recognized at an early stage. Glaucoma’s progression damages the optic nerve, the bundle of nerve fibers carrying information from the eye to the brain, which leads to vision loss or complete blindness.

Vision loss from glaucoma is irreversible.

In medicine, the word "cure" is not bandied about lightly. But there is exceptional hope, and then some, in what Dong Feng Chen, MD, PhDARVO Fellow has uncovered. It’s a molecule—not named here to protect IP—found in the human body that can produce the cure for this disease.

For a long time, Chen, an associate scientist at Schepens Eye Research Institute at Mass Eye and Ear and associate professor of ophthalmology at Harvard Medical School, has been studying the mechanisms that control neurodegeneration and nerve regeneration in the retina and brain. Her work is leading to treatments not only for neural injuries (trauma) and diseases, such as glaucoma, but also ischemic optic neuropathy and Alzheimer’s disease.

Partly funded with a Mass General Brigham Summit Fund grant of $500,000, Chen’s promising research centers on what she first explored in mice. Her earlier work achieved full-length optic nerve regeneration from the eye in genetically engineered neonatal mice and uncovered new immune and T-cell-mediated autoimmune mechanisms, underlying neuron loss in glaucoma, and ischemic optic neuropathy.

In an effort to translate her earlier work to the study of glaucoma, her lab developed a method of inducing glaucoma in lab animals, like mice, by injecting safe and biocompatible polystyrene microbeads into the anterior chamber of the eye; it was among the first to do so.

As glaucoma is often associated with elevated eye pressure, their model mimicked the disease process of humans. Moreover, the mice exhibited progressive neuron loss after the intraocular pressure has returned to normal, like what is noted in patients who continue to lose sight after eye pressure is medically controlled at a normal range. Chen hypothesized that increased intraocular pressure might not necessarily be at the root of the disease.

A prior published study had found that some 90 percent of glaucoma patients in Japan and a large number of patients in other parts of Asia, for example, had normal intraocular pressure, a medical mystery. High intraocular pressure is recognized as one of the risk factors and the only one known to be modifiable medically, but elevated eye pressure is not always associated with glaucoma. Other risk factors include old age, non-white race, and a family history of the disease. In other words, glaucoma does not always present with increased intraocular pressure.

To test this theory, the Chen lab raised the intraocular pressure in subject mice to 25 mm of mercury. In humans, a reading above 21 mm mercury is considered high intraocular pressure. What they found in the experiment was the increase caused stress on the neurons, which, in turn, triggered an immune response, including a T-cell response. That immune response attacked the optic nerve causing the glaucoma. In mice that have weakened immune responses, such as mice lacking functional T cells or never having been exposed to bacteria (germ-free), increased eye pressure causes much less or no nerve damage at all.

This might explain why some patients have normal intraocular pressure with glaucoma. Perhaps, they have a more intensified immune response that can attack neurons under normal pressure. Targeting the immune process became the answer.

A company is created

FireCyte was founded by Chen and Bill Yelle, a former entrepreneur in residence at Mass General Brigham Ventures and now CEO of FireCyte. The emerging biotechnology company is developing novel treatment strategies focused on the role of microglia and neuroinflammation in progressive neurodegenerative diseases of the eye.

Chen credits Meredith Fisher, PhD, Mass General Brigham, partner of the Innovation Fund, in helping secure funding and in shepherding the innovation into the spinoff. It was Fisher who recognized the innovation and newco opportunity, including attending a glaucoma conference, where a vice president of R&D from a large pharmaceutical company had heralded Chen’s research as "the most exciting development in glaucoma research in years."

“Dong Feng’s and her collaborators’ research redefined glaucoma as an autoimmune disease and uncovered a novel therapeutic strategy,” said Fisher. “This work represents not just innovative new science but an opportunity to create a first-in-class therapeutic for neurodegenerative eye diseases, which currently have few treatment options.”

The road ahead for FireCyte includes clinical trials that could last up to five years; a reasonable timeline is estimated at eight or nine years before a therapy, an injectable at first, would be available to patients. A pill form could come later.

More on Mass General Brigham Innovation

“Without the help of the Innovation staff, none of this would have been possible,” says Chen. “As scientists, our expertise lies in science and academics; we lack connections with the business world and the knowledge to build companies. Jumping from basic science to starting a company—that’s a different career. I have such great respect for Innovation.”

Fisher introduced Chen to Dione Kobayashi, PhD, head of therapeutics and operating partner, Amplify, another advocate who helped Chen, including crafting her presentations informing the technology. The two have known each other for decades.

“Dr. Chen is a phenomenal scientist and innovator,” says Kobayashi. “She brings a deeply rigorous and yet creative approach to her work, and this has enabled her to make discoveries on neuroimmune mechanisms that will help patients with glaucoma and other ocular disorders.”

The first contact with Innovation, however, was with Eugenia Park, PhD, manager of business development and licensing, who believed in the project and understood the technology that set the wheels in motion.

“Dong Feng is not only an accomplished scientist; she is also a pleasure to work with,” says Park. “She is adaptable and gracious regardless of the situation, whether it is with her trainees or with pharmaceutical executives.”

Beyond first-in-use technology

“If we think about glaucoma as a prevalent neurodegenerative disease, we also think of Alzheimer’s disease, Parkinson’s disease, those in the brain. But the most prevalent neurodegenerative disease is in the eye, glaucoma,” says Chen.

The eye remains an excellent entry point for developing this treatment, Chen believes, noting that the neuroprotective strategies for treating neurodegenerative diseases like glaucoma may relate to many neurodegenerative diseases because they share commonalities in pathogenesis, which means the immune response underlines the neurodegeneration.

“Dong Feng is an innovative thinker, an outstanding scientist, and a terrific co-founder,” adds Fisher. “We at Mass General Brigham Ventures are excited to be an early investor in her work and to be alongside the company (FireCyte Tx) as it advances her research to create new medicines for eye disease.”