Giving Sight to the Blind: First Treatment for Leber Congenital Amaurosis Gains FDA Approval

On Tuesday, December 18, 2017, the United States Food and Drug Administration approved the first ever gene therapy for an inherited disease. Patients with a type of Leber congenital amaurosis (LCA), a blinding childhood eye disease, due to mutations in the RPE65 gene will now be able to receive treatment to improve their sight. This is a landmark day, and one which countless scientists, physicians, and patients have worked toward for decades.

LCA is a genetic condition which causes severe vision loss and blindness in childhood. Affected children are often born with very poor vision, and parents may notice their child never seems to make eye contact, has roving eye movements, or nystagmus, where the eyes shake back and forth. Almost all LCA is autosomal recessive, meaning each parent is a carrier for the disease, that each child of these two parents will have a 25% risk of developing the disease, and that affected individuals have a <1% chance of passing it on to their future children. Until the late-2017 FDA approval of voretigene, there were precisely zero commercially-available treatments for LCA.

Fortunately, and miraculously, this is changing.

Scientists have developed a treatment, called voretigene neparvovec (Luxturna is the trade name), which can be given to patients with this specific type of LCA. This treatment is a type of gene therapy, which means that the correct version of the defective gene is given to the patient, allowing the RPE65 protein product to perform its normal function in the eyes (RPE65 is an enzyme involved in recycling Vitamin A in the visual cycle).

Voretigene makes use of a benign virus to carry the correct version of the RPE65 gene into the patient's eyes. The patient undergoes a surgery, under general anesthesia, during which voretigene is injected very carefully, by highly trained vitreoretinal surgeons, underneath the retina.

I have seen several patients who underwent this treatment during voretigene's clinical trial. I was very impressed with the results -- children with no functional vision were suddenly able to see well enough to navigate the room. Results from the phase 3 clinical trial were published recently in the prestigious journal Lancet, with my friend and training mentor Dr. Stephen Russell of the University of Iowa as the lead author.

Voretigene represents a historic breakthrough on multiple levels. Not only is it the first medical treatment for a previously untreatable disease, allowing blind people to see for the first time, but it is also the first gene therapy for an inherited disease of any kind. It will also pave the way for future research and development of similar treatments for similar diseases. As a pediatric ophthalmologist and inherited eye disease specialist, it is difficult to overstate how excited I am about this! 

Curious as to what kind of a difference this treatment can really make? Check out these next two videos. The first shows a boy with RPE65-LCA trying to navigate an obstacle course prior to his treatment. Notice how much he struggles.

Now, watch this same boy, a few months after treatment with voretigene, navigating a similar obstacle course. It's a night-and-day difference!

The future is bright for people with LCA and other inherited eye disease, and I enjoy dedicating part of my practice to holding a special clinic just for patients with these conditions.

Stem Cells and Treatment of Eye Disease

An article published online today in The New England Journal of Medicine has quickly gained recognition within both the scientific community and among the public. The report, published by Ajay E. Kuriyan, MD and colleagues describes three elderly women with macular degeneration who were treated at a so-called "stem cell clinic" in South Florida with the hope that they would regain vision. Tragically, not only did none of the three have any improvement in their vision, but each suffered severe, permanent vision loss as a result. Each went from having vision good enough to drive to being legally blind. 

This clinic, operated by an entity known as U.S. Stem Cell, claims to have treated many patients with all sorts of different ailments (e.g. knee injuries, heart failure, neurological diseases) with "stem cells," which they purport to obtain by removing fat from the patients' own bellies and then purifying this fatty tissue into stem cells (author's note: I have no idea whether they obtained actual stem cells or not, and I'm highly suspicious that whatever they produced wasn't exactly "100% pure," shall we say).

At this center, these cells are then injected into various body parts -- in the macular degeneration patients, directly into the vitreous gel which takes up most of the volume within the eye -- in order to treat the patient's disease.

As an ophthalmologist, I have been asked by patients and friends in the past about similar stem cell clinics, and so I researched them. I quickly realized that what they were selling was scientifically unsound at best, and potentially dangerous at worst, and I advised any who have asked me to stay away and tell their loved ones to do the same. Reading this New England Journal article, I was very sad to see that my concerns were justified.

The three women reported in Dr. Kuriyan's paper not only had both eyes injected under this extremely unvalidated and highly unscientific approach, they had it done to both eyes on the same day, thus exposing both eyes to a risky, unproven therapy -- and they paid $5,000 to do so.

Now, "Who would ever do that?" you might say. And I agree with you, to a point: I certainly never would, and I hope you wouldn't either. But I can understand how it could happen, from a patient's perspective. I dedicate part of my practice to caring for patients with inherited eye diseases, and I see patients with severe vision loss who are desperate for anything to help improve their vision. I regularly speak with family and friends of people who are really struggling with terrible eye diseases, and they so badly want to find something to help. I understand that -- we all feel that way when people we love are hurting.

And this is one of the things that makes me so angry at the people involved in providing this "stem cell treatment." Using pseudoscience (we'll get to this below), they prey upon people's desperation, charge them a not-insignificant sum of money, and offer a solution which any scientist worth his or her salt would immediately recognize as highly suspicious/utter junk.

But that's not the only reason this makes me angry.

As a scientist who has studied and worked and trained with world-leading researchers at the University of Iowa, I believe that stem cell technology -- appropriately developed, studied, and applied -- is an incredibly promising area. But it will not involve sham clinics where patients are treated for all sorts of different diseases with the same "stem cells." It will not involve patients paying money for experimental treatments. It certainly won't involve having both eyes injected on the same day, and the first patients treated will not be patients -- like these three women -- who had useful vision to begin with, and thus, much more to lose.

Let's discuss stem cells for a minute, because stories like these give this technology a bad name and can erode public trust. In 2012, Japanese physician scientist Shinya Yamanaka was awarded the Nobel Prize in Physiology or Medicine for his groundbreaking discovery that adult, mature skin cells could be reprogrammed to turn back into stem cells. These cells are called induced pluripotent stem cells (iPSCs), because they have been induced into becoming cells that can then become a variety of different tissues, like brain, heart, eye, or liver, for example. Think of stem cells as cells that haven't yet decided what they want to be when they grow up.


Scientists and physicians in all different areas of medicine are excited about iPSCs because of the possibility that a patient's own skin cells could be reprogrammed first into stem cells, and then developed into cells, tissues, and even organs that the same patient could receive as treatment. For example, could we develop new heart muscle cells and transplant them into patients with damage from a prior heart attack?

iPSCs are different from traditional stem cells in two important ways. First, when you think of "stem cells," you probably think of embryonic stem cells, which come from human embryos, and have serious ethical concerns inherent in their use. iPSCs are a totally separate thing -- no embryos are involved at all -- it's just the patient's own skin! Second, because the iPSCs come from the same person who would then receive them as treatment, the cells are immunologically matched, meaning the patient's body won't reject them as foreign, so they won't need to take medicines to suppress their immune system for the rest of their lives.

A number of other cutting-edge technologies could be realistically be coupled with iPSCs to help patients suffering from blinding eye diseases. CRISPR, which is short for clustered regularly interspaced short palindromic repeats, is derived from a bacterial immune system of sorts, whereby bacteria recognize and cut out foreign DNA they have acquired before it can harm them. This same concept can be applied to human cells, allowing for the genome to be edited; using it, a harmful or dysfunctioning gene can be removed, and a corrected version inserted. A patient blind from a genetic eye disease could have stem cells made from their own skin, could have the genetic defect that caused blindness corrected via CRISPR in these cells, could have the cells differentiated into retinal precursor cells, and could then have these cells transplanted into their eye.

And instead of injecting them into the vitreous gel within the eye, and hoping (against all hope) that somehow they make their way where they are supposed to go, ideally, these cells could be placed within a special biopolymer created via a 3D printer that would keep them in perfect alignment and orientation, and then this could be surgically implanted underneath the patient's retina, exactly where the cells belong. 

Researchers at the Wynn Institute for Vision Research at the University of Iowa are pioneering this exciting science. With the help of philanthropic donations, they planned and constructed their own Good Manufacturing Practices laboratory, which is a facility with the highest imaginable standard of cleanliness and sterilization, and the type of laboratory required by the FDA for developing things like iPSCs for transplantation into humans. Here is an article on PubMed describing some of their recent work.

Properly developed and validated, stem cells hold tremendous promise for dramatic advances in medicine. What the charlatans down in Florida have done in this stem cell clinic is akin to someone hearing that "chemotherapy" is a treatment for cancer, and then cooking up some "chemotherapy" in their basement -- without regard for whether the medicine is the right type for the patient's specific type of cancer, whether it is safe, whether it has been tested adequately, etc. etc. etc. -- and telling the patients to bathe in it. Of course it isn't going to work! And not only that, but anyone who hears about it will likely come away thinking "chemotherapy" doesn't work and is really dangerous.

Just like chemotherapy isn't a cure-all, stem cells won't fix everything. Just like chemotherapy, stem cells need to be cautiously studied and judiciously employed. But just like chemotherapy, stems cells hold tremendous promise for treating patients with heretofore untreatable conditions. We should be extremely wary of anyone advertising stem cell treatment at a cost. But we should also realize that stem cells -- namely, iPSCs -- truly represent an area of incredible potential for treating dozens and perhaps hundreds of devastating human diseases safely and effectively.