BACKGROUND: Glaucoma is a complicated diseasewhere damage to the optic nerve leads to progressive, irreversible vision loss. It is the second most common cause of blindness in the United States. Everyone is at risk for glaucoma, there may be no symptoms to warn you, and there is no cure for the disease. It is estimated that over 2.2 million Americans have glaucoma but only half of those know they have it. (Source: Glaucoma Research Foundation)

TYPES:  There are four major types of glaucoma:

·         Open-angle (chronic) glaucoma –An increase in eye pressure occurs slowly over time. The pressure pushes on the optic nerve. Unknown cause, tends to run in families

·         Angle-closure (acute) glaucoma- occurs when the exit of the aqueous humor fluid is suddenly blocked. This causes a quick, severe, and painful rise in the pressure in the eye. This is an emergency, and if you have had acute glaucoma in one eye, you are at risk for an attack in the second eye.

·         Congenital glaucoma- seen in babies and present at birth due to abnormal eye development.

·         Secondary glaucoma- caused by drugs like corticosteroids, eye diseases, systemic diseases, or trauma. (Source: www.ncbi.nlm.nih.gov)

TREATMENT:  A dilated eye exam is the best and most effective way to detect glaucoma. Treatment can’t cure glaucoma, but it can prevent and avoid further vision loss. Different treatments for glaucoma include medicated eye drops, oral medications (usually a carbonic anhydrase inhibitor), Drugs that protect the optic nerve, and surgery to lower eye pressure. Advocates of medicinal marijuana cite evidence that hemp products can lower intraocular pressure (IOP) in people with glaucoma. However, these products are less effective than medicines prescribed by an eye doctor. Additionally, side effects of long term use of marijuana can override any potential benefits. (Source: Mayo Clinic, Glaucoma Research Foundation)

NEW TECHNOLOGY:  Neurotech's product, NT-501, contains encapsulated human cells genetically modified to secrete ciliary neurotrophic factor (CNTF). CNTF is a growth factor that is able to rescuing dying photoreceptors and protect them from degeneration. NT-501 is designed to continually deliver a low, safe and therapeutic dose of CNTF into the back of the eye, and is designed for the potential treatment of retinitis pigmentosa (RP) and age-related macular degeneration (AMD).(Source: Neurotech)

Dr. Jeffrey Goldberg, associate professor of ophthalmology at Bascom Palmer Eye Institute at University of Miami, talks about a new approach that could reverse vision loss

Tell us about this trial. It seems pretty exciting to slow down or even restore vision for people that have glaucoma.

Dr. Goldberg:  Absolutely. We are very excited about it. The treatments in glaucoma have really focused on treating intraocular pressure, or eye pressures. We know that for most patients if we can lower their pressures with medicines or with surgery, we can slow or in some cases, maybe even halt the progression of the disease. But certainly, we have some patients for whom lowering the eye pressure is not enough, or they cannot tolerate all of the eye drops, or the surgeries do not work for them. We also have some patients whom we just catch too late in the disease and they have already lost significant vision. For these groups of patients in particular, we really want to find new treatments, new ways that we can prevent vision loss or even bring back vision that they have lost, which traditionally we have not been able to do in glaucoma. There have been a number of new treatment ideas, approaches, drugs that have been tested, and look like they work really well when we look in preclinical models, but transitioning those to clinical trials has proven challenging. We have started a trial here taking advantage of one of these drugs, a molecule called ciliary neurotrophic factor or CNTF. It turns out that it is expressed all through the eye and the brain, but we might argue not in high enough amounts. A company in Rhode Island, Neurotech, devised a way to deliver it inside the eye using a little implant, and we have been testing this now in patients with glaucoma.

And this study also takes an interesting turn looking at glaucoma as not just an eye problem, but a neurological problem as well, correct?

Dr. Goldberg:  Absolutely.

Why are you taking that approach?

Dr. Goldberg: Glaucoma is a neurodegenerative disease. The focus has, of course, been on really the front of the eye where eye pressure is controlled, so all of the treatments so far have focused on the front of the eye. But the loss of vision occurs because we lose the fibers that connect the eye to the brain in the optic nerve, and that is really the only highway carrying visual information from the eye to the brain. Those fibers are called “axons” and they are attached to neurons or cells in the retina that are collecting all of the information about the visual world. Those retinal cells are called “retinal ganglion cells.” The retinal ganglion cells degenerate in glaucoma just like other very specific cells in the brain or spinal cord degenerate in other neurologic disease like Lou Gehrig’s disease or Parkinson’s disease or Alzheimer’s disease. Not only that, we have begun to appreciate that the neurodegeneration that happens in glaucoma bears a lot of similarities to the neurodegeneration that happens in these other degenerative diseases. There is a loss of connectivity from cell to cell. The neurons stop talking to each other. There is some sort of injurious process which for glaucoma, we still do not really understand. Then we have a slow degeneration, a slow loss of these cells where they dysfunction initially and then eventually die. So thinking about the disease in this way has allowed us to open our minds to new treatments. Treatments that are not just about eye pressure, but may also be about protecting these cells from dying or protecting the fibers from dying or even encouraging these fibers to regrow or regenerate back through the optic nerve and reconnect back to their targets in the brain.

How does CNTF do that?

Dr. Goldberg: CNTF is a protein that is expressed normally in the visual system and it is a called a trophic factor. It normally signals survival and growth of retinal ganglion cells and their axons. It has been long demonstrated in a variety of preclinical models that if you have an injured optic nerve and you give extra CNTF, usually just by injecting it into the eye, that you can increase the survival of retinal ganglion cells and also encourage their axons, those fibers in the optic nerve, to regrow back towards the brain. CNTF gets bound and taken up by the retinal ganglion cells and perhaps by some of the neighboring cells around them that help feed the retinal ganglion cells all the good things that they need to survive and grow. It sets off a signaling pathway inside the retinal ganglion cells that encourages their growth.

How does it know when to release some CNTF?

Dr. Goldberg:  This particular delivery system is really ingenious.  It saves us having to inject the CNTF into patient’s eyes over and over and over again over the course of months or years. The delivery system is a small capsule. We insert it through the white part of the eye, called the sclera, into the jelly in the center of the eye, called the vitreous, where it stays inside. Inside of this little capsule, there are little human cells, not stem cells but similar, a “cell line,” and the cells have been engineered to express CNTF. They make the CNTF constantly and pump it into the eye. By implanting this little capsule, patients are actually getting exposed to a low level of CNTF over a long-term; certainly we think over months and perhaps years. Now, we do not know if it is enough CNTF. We do not know if it is enough to have a positive effect, we are just taking the early steps towards eventually testing whether it is effective in this and other diseases, but it still is laying for us a model for how to move forward translating what we have learned in preclinical models into patient trials.

What did you see in preclinical trials?

Dr. Goldberg: Preclinical trials have been really remarkable. Much of the work has been done in rats or mice, although sometimes larger animal models have been tested. In these various models, if you injure the optic nerve, whether by increasing the eye pressure as would happen in glaucoma or even physically damaging the optic nerve, normally the retinal ganglion cells first of all fail to regrow their axons past that injury site in the optic nerve. Then shortly after, the retinal ganglion cells start to die. And, what we have seen in countless preclinical models performed in our lab and many other labs around the country and around the world is that CNTF can slow that death or prevent some of those cells from dying. Furthermore where normally there is no axon regeneration into the optic nerve, with CNTF there is regeneration into the optic nerve.