Developing a New Arsenal to Fight Glaucoma
Q & A with Dr. Jeffrey Goldberg, Head of New Clinical Trial
This research was supported by BrightFocus
Q. What got you interested in neuroprotection as a way to fight glaucoma?
A. I treat patients with glaucoma in clinic and in the operating room, and essentially all of our therapies are directed at treating the intraocular pressure regulated at the front of the eye. But my research has always focused on the retinal ganglion cells (RGCs) in the back of the eye and their axon fibers carrying visual information down the optic nerve back to the brain. We have no approved treatments that address the degeneration of the RGCs or their axons, so this is a huge unmet need.
Q. Were you involved in the initial discovery/development of ciliary neurotrophic factor (CNTF)? How was it discovered that CNTF might work for glaucoma?
A. CNTF was first isolated and characterized as a survival/growth factor for neurons in the 1980s. Since that time many laboratories have studied CNTF in retinal ganglion cell survival and growth signaling in animals from mice to monkeys, including in animal models of glaucoma. My group has also contributed to this work over the last 15 years.
Q. Is CNTF) approved for any other diseases? Do you think it might have benefits for other diseases of mind and sight?
A. CNTF had been studied over a decade ago for motor neuron disease and obesity, using subcutaneous daily injection to deliver it to the whole body, and using the NT-501 implant that delivers it to the eye has been studied in age-related macular degeneration (AMD) and retinitis pigmentosa as well as macular telangiectasia in a study still ongoing. CNTF is a powerful growth factor, but it has not been approved for any diseases yet. Being able to deliver it directly to the eye, without significant exposure to the rest of the body, is a significant advantage of the NT-501 implant approach.
Q. In your trial, will you be happy if the visual field is maintained, or are you expecting to see improvement?
A. Both of these, neuroprotection and neuroenhancement, are very much on the table. We have designed the clinical trial to detect either or both, so we are well-prepared. It will be an enormous step forward if either of these can be demonstrated.
Q. Is there a down side? Are there any noticeable side effects or adverse events to CNTF?
A. The patients have a little irritation from the surgical implant for about a month, and after that the pupil can be a little smaller, but this CNTF implant has not been a source of serious adverse effects to date. Of course all patients have to understand that these are still early days, and there could be adverse events as yet unrecognized.
Q. At a recent vision conference, there was a debate over whether research funding “eggs” should be placed in the neuroprotection or neurogeneration “basket.” What’s your view? Do you line up behind one or the other, or both?
A. The truth is, as a field we have made enormous progress in identifying promising candidates that may be neuroprotective, neuroregenerative, or neuroenhancing. There is of course still much to do on the discovery side with basic research, but so many discoveries today need to be moved towards human testing to see whether they will help our patients. Certainly the therapies that are neuroenhancing—eliciting an improvement in vision in the short term—will be easier to study and detect effects in clinical trials of reasonable size and duration. But I believe with improved clinical trial design and newer biomarkers we’ve developed to track and even predict progression, we will be able to test many more of these promising therapies in this next phase of development.