LA JOLLA — For about 300 American children who suffer from the rare and historically fatal kidney disease cystinosis, Dr. Jerry Schneider symbolizes hope.
Schneider, a UC San Diego Medical School professor, is one of the world's few experts on the disease, and in a weeklong conference here that ended Friday, he and his colleagues shared with about 20 families their research on a drug with the potential to extend and improve the lives of those with cystinosis.
The UCSD conference was also a chance for parents to share their stories of love and hardship about caring for offspring with the disease and for the children to discover that they are not alone.
Cystinosis is a rare genetic disease that occurs worldwide, with about 30 new cases in the United States each year. The disease impairs the kidneys' ability to break down the amino acid cystine and leads to eventual degeneration of the kidneys.
Schneider said that children who have the inherited problem appear normal at birth but develop signs of cystinosis within six to eight months, usually beginning with sugar in the urine, consumption of large amounts of water and evidence of rickets.
If not diagnosed properly or left untreated, children will die within a couple of years. Symptomatic treatment--continually replenishing water and salts--allows children to live several years, usually to age 9 or 10, although growth is severely stunted. A 6-year-old with the disease usually is no taller than a normal 3-year-old.
By age 10 or so, Schneider said, the ability of the kidneys to filter the amino acid has failed completely and a kidney transplant is required to keep a child alive. But even with a transplant, the rest of the body continues to suffer from the buildup of cystine, and vision problems--especially light sensitivity--and neurological damage become evident by the time patients enter their teens.
The symptoms of the disease were first noted in the 1930s by several European pediatricians. Not until the 1950s, however, were the tissues of children with the symptoms discovered to be full of cystine crystals.
The conclusive evidence of cystine concentrations as the culprit opened the doors to research that Schneider has widened during the past two decades.
About 10 years ago, Schneider and his UCSD laboratory colleagues discovered that the drug cysteamine would dissolve the amino acid out of white cells.
The research involved tedious trial-and-error experimentation. "We added one chemical after another to skin cells grown in dishes, waited a few hours and then measured the (amino acid) content to see if there was a change," Schneider recalled in an interview. "And when we added this one chemical, we found a marked reduction."
The drug has been studied now to the point where any child diagnosed with the disease is eligible to receive it, either through an ongoing study at UCSD or through a parallel, but smaller, study at the National Institutes of Health (NIH) in Washington.
"The treatment really seems to be helping; it's clear that the drug is quite effective," Schneider said. "But the frustrating thing is that it could be even more effective if we could start it right at birth. Yet, you often can't make the diagnosis until some significant kidney damage has occurred, making it too late to repair the damage. Then you can only use the drug to prevent further (degeneration)."
While Schneider has devised tests to detect cystine buildup in babies either during pregnancy or at birth, he said they are expensive and time-consuming and cannot possibly be done en masse, given his limited research funds.
"We do know . . . that the chance of having a child with cystinosis is small if (a carrier) marries someone who is not a carrier," Schneider said.
Because the drug has become common only recently, almost all of the children who take it regularly were diagnosed after birth and have already suffered some degenerative problems. These children are being studied to learn whether the drug will stop further kidney damage and whether the drug, if administered from birth, can prevent the need in later years for kidney transplants.
A second NIH study has just begun which involves older children, who already have had kidney transplants, to see whether subsequent vision and other damage can be prevented.
While cysteamine has no serious side effects, it has "an incredibly bad taste and smells like rotten eggs," Schneider said. Furthermore, the drug must be taken every six hours indefinitely, he said. A new odorless and tasteless version of the drug is being prepared for use later this year. Schneider hopes that if the new drug proves as effective, it will increase compliance among children.
"We have had between 10% and 15% of the children who started the study withdraw because of the terrible taste and smell," he said. "And we are not sure how many take it all the time."
Because the disease is so rare, Schneider has always had to scrape for funding.
"There is no cystinosis institute like there is a cancer institute," Schneider said. "Most of us up until now have been able to get adequate funding but it always has been a struggle. And it's always been much harder to get funding for (clinical studies) than for basic research."