Brain Disorder Treatment Hailed
Researchers at Good Samaritan Hospital on Wednesday reported the first successful use of fetal cell transplants to treat Huntington’s disease, offering hope for the first effective treatment of the fatal brain disorder.
Dr. Deane B. “Skip” Jacques and his colleagues told a meeting of the American Academy of Neurology in San Francisco that the transplants halted progression of the disease in the three patients treated and reversed some of the deterioration that had occurred.
Although the patients need to be studied longer to ensure the survival of the grafts, “I think we could impact Huntington’s in a revolutionary way,” said Dr. Matthias Kurth of the Barrow Neurosciences Institute in Phoenix, who evaluated the patients.
Matthew Hopson, a 24-year-old from Phoenix who received the first graft in July, put it more succinctly: “It saved my life.”
Huntington’s is one of the more common inherited brain disorders. About 25,000 Americans have it, and an additional 60,000 carry the defective gene and will develop the disorder as they age. The slowly progressive condition, which killed folk singer Woody Guthrie, usually comes on between the ages of 30 and 50 and causes the degeneration of brain cells.
It is characterized by jerky, involuntary movements called chorea, loss of control of bodily functions, and dementia, a progressive deterioration of memory and thought processes. Children of patients have a 50% chance of developing the disorder, which is invariably fatal within 10 to 15 years after onset.
Although researchers hope to develop therapies based upon the discovery three years ago of the defective gene that causes Huntington’s, no effective therapy exists. Success with transplants would represent a major step forward in improving the condition of Huntington’s patients.
Fetal cell transplants are being widely studied as a treatment for Parkinson’s disease, and the Good Samaritan group is one of the leaders in that effort.
Jacques’ team has performed the procedure on 40 patients and reports in this month’s Journal of Cell Transplantation that 70% of them have shown significant improvement in neurological functions. The remaining 30% are now taking less medication for their Parkinson’s, and none have deteriorated as a result of the transplant.
Animal experiments suggest that Huntington’s may be a much better prospect for transplants than Parkinson’s, said Dr. Oleg V. Kopyov of Good Samaritan. In Parkinson’s, the transplanted cells serve simply as a source of brain hormones, particularly dopamine and growth factors.
But in animal models of Huntington’s, the transplanted cells actually become integrated into the brain’s structure, restoring neural circuitry that was destroyed by the disease. “It lends itself better to transplants than anything else in the brain,” Kurth said. Although several groups have talked about performing the transplants, no one has yet reported any results.
The Good Samaritan team actually performed their first transplant a little sooner than they had planned when Kurth told them about Hopson. He is an unusual Huntington’s patient in that his first symptoms appeared early, at age 20, and the disease progressed very rapidly.
Researchers now know that this early onset is a function of the degree of mutation in the Huntington’s gene, and Hopson’s gene is, in fact, severely mutated--much more so than the gene carried by his father. The elder Hopson, 48, has not yet developed the disease.
By the time that Hopson underwent surgery in July, he was bed-bound, said his mother, Sherry Cauldwell.
“If he tried to walk, he fell, and he had bruises and cuts all over his body,” Cauldwell said. “We had to spoon-feed him. He had tremors in his voice so bad that his speech was incomprehensible, which really made it difficult because he also couldn’t write.”
Kurth was examining Hopson every month and it became apparent that he was declining rapidly. “He had maybe five years of life left, which weren’t going to be very pretty,” Kurth said. He discussed the case with Jacques “and Skip said, ‘Why don’t we do a transplant?’ ”
The results from the surgery surprised even the research team. “Our expectations were exceeded a lot,” Kopyov said. “We couldn’t expect what we obtained.”
Within 10 days after the surgery, Kopyov said, Hopson was walking and talking and had no chorea. “We thought it was a placebo effect, but we now know that it isn’t,” the doctor said. “But we still don’t know how to explain such immediate improvement.”
The two other male patients operated on in January showed the same type of immediate improvement, but “it was even more pronounced,” Kopyov said.
Hopson has continued improving and is now living independently with a roommate. He uses a wheelchair, but can walk short distances and rides an exercise bicycle.
“I miss playing Frisbee and all that stuff . . . but I can go anyplace I really want to,” he said. “I’m slowly but surely getting better.”
“What we can say with confidence,” Kopyov said, “is that the disease is not progressing any more.”
The team plans no more transplants for perhaps another year while they evaluate the current patients’ progress. They also do not have funds to perform further surgeries. But if the patients continue to show improvement, Kopyov said, that problem will probably resolve itself.
