Some U.S. experts say there is no evidence that the stem-cell therapy being offered in China will work in one of the most common causes of childhood blindness, optic-nerve hypoplasia (ONH). We asked Dr. Mark Borchert, head of the vision center at Children's Hospital Los Angeles, to explain more about the disease and possible treatments.
What is ONH?
Optic-nerve hypoplasia is a failure of development of the optic nerves of one or both eyes. It's associated with the failure of development of the connections of the neurons with parts of the brain. ONH is a major cause of congenital blindness in children.
What causes it?
We do not know what causes it. We know that it is almost certainly not genetic.
Is it on the rise?
Most of us in pediatric ophthalmology who see a lot of children with congenital blindness think it's increasing in frequency. We don't have good statistics in the U.S. on the prevalence of vision loss in children. But statistics from Europe, especially the Scandinavian countries, show it is the only cause of visual impairment — congenital visual impairment — that is actually increasing. All the other causes are decreasing. But we don't have good information for the U.S.
ONH is not just blindness, is it?
Not at all. It's a brain-development problem. Children with optic-nerve hypoplasia have a whole host of systemic and neurological problems. The most obvious are problems in controlling the pituitary gland, which controls most of the hormones in the body, including sex hormones, growth hormone, steroid hormones for your body to deal with stress, thyroid hormone, and anti-diuretic hormone. Of these children with ONH, about 80 percent have abnormal function of their pituitary gland and ultimately need some sort of treatment with replacement hormones.
In addition to that, children with ONH have a lot of developmental problems — learning disabilities, motor disabilities and speech and communication problems. And these often don't become apparent until the child is a little older, sometimes long after the diagnosis of optic-nerve hypoplasia has been made.
Does treating the hormone problems help with vision?
We don't know the answer to that. We're in the process of studying that right now. There's certainly a suggestion that early recognition and treatment of some of the hormone problems leads to better outcomes — in particular, early recognition and treatment of the thyroid-hormone deficiency. However, the children with optic-nerve hypoplasia have thyroid-hormone dysfunction due to a problem with the hypothalamus that controls the pituitary gland. And hypothyroidism due to this is not picked up with the current neonatal-screening procedures.
Consequently, the hypothyroidism in these children is not detected until after the optic-nerve hypoplasia is detected, and that is usually when the child is old enough for the parents and doctors to recognize that there's a vision problem. That's usually at several months of age and is too late to prevent the major effects of hypothyroidism. Presumably, if you could diagnose them earlier with a better neonatal-screening test you could prevent a lot of the cognitive and intelligence problems that afflict these children. We're also doing studies on whether or not early treatment with thyroid hormone or growth hormone impacts their vision development or their cognitive development as well as their growth.
What happens in children who are getting an experimental treatment?
We currently know that regardless of whether or not they are treated, at least 50 percent of children get some improvement up until five years of age. We don't know whether they can improve beyond that.
So it's hard to tell if a treatment is working or if they're just improving naturally?
Absolutely, and that's why a controlled study needs to be done, such as we're doing with the growth-hormone study. We're trying to determine whether it's the growth hormone that's actually improving their vision beyond what they would normally improve.
In those who do improve, how much better is their vision?
Most children do not have a miraculous improvement. A child will not go from light perception to 20/40 vision or driving vision or reading vision. That would be extremely unusual. However, it is extremely common for children to go from no light perception or bare light perception to being able to see very large objects, such as automobiles, or being able to navigate around a room without a cane or a dog.
What are you telling parents who are asking about the Chinese stem-cell therapy?
That I have two problems with this therapy.
First, from a scientific point of view, there is no evidence that cord-blood stem cells can ever form neurons, at least not in any peer-reviewed scientific literature. And I can assure you anyone doing legitimate research in this area is not withholding information to the contrary, because obviously this would be a major breakthrough if neurons could form from cord-blood stem cells.
Even if they could form neurons, there's no evidence that these neurons could ever make it to the eye where they could form new ganglion cells that are the cells that form the optic nerve, because the eye is a very protected environment from foreign material.
Second, from an ethical point of view, it is really not appropriate to be treating children who cannot give assent to the procedure themselves with a therapy that has no basis even in the laboratory for its use. Also, there are real risks with any procedure in which you are injecting foreign material into the body, especially if you're injecting it into the cerebrospinal fluid, which is my understanding of what they're doing in China. Because this foreign material can cause inflammation, can cause meningitis and cause serious brain injury.
It's also an ethical problem because I do not think that thorough and formal consent is obtained.
Finally, there's no scientific oversight of this work. In this country and Europe, this type of research could never be done without scientific oversight, even making sure that they're actually doing what they say they're doing. There is no way of knowing that they're actually purifying stem cells appropriately, that they're injecting stem cells, that they have any sort of monitoring of adverse affects from this. So this is really an inappropriate way to do any research, especially on innocent children.
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