Treatment for Huntington’s Disease Shows Promise

French researchers have successfully reversed the course of Huntington’s disease in three of five patients by implanting fetal brain cells into their brains.

Several research teams have previously attempted the feat, but the French results are the best to date, experts said.

“This is a very promising preliminary result, even though it is a small number of patients,” said Dr. Christopher Ross of Johns Hopkins University, medical and scientific director of the Huntington’s Disease Society of America.

Brain transplants have been poorly studied because of controversies involving the use of fetal cells and their limited supply. This situation may change soon, however, because of the growing ability of scientists to convert stem cells--primitive cells that have the capability of growing into a variety of mature cells--into brain tissue.

“This [transplant] approach is a lot more attractive than it was a couple of years ago because of the possibility of using stem cells,” which will be much more widely available than the fetal cells that were used in the experiment, Ross said.

The research is scheduled to be published in Lancet next month, but was posted on the journal’s Web site (https://www.thelancet.com) Wednesday after the French government released information about the experiments.

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. It strikes between the ages of 30 and 50 and is characterized by jerky, involuntary movements called chorea; loss of control of bodily functions; and dementia, a progressive deterioration of memory and thought processes.

Researchers identified the gene that causes Huntington’s in 1993, but have not yet developed an effective therapy based on that discovery.

The idea of implanting fetal brain cells into the brain began with Parkinson’s disease, where it has been relatively successful. But Parkinson’s disease involves the death of a comparatively small number of brain cells that secrete a specific chemical called dopamine, and the implanted cells are viewed primarily as a new source of that brain hormone.

Huntington’s represents a more difficult problem because it involves the widespread death of cells. Experiments in animals have shown that transplanted cells can grow and thrive in the host brain, becoming integrated into the brain architecture. But that has not previously been clearly demonstrated in humans.

Several teams have reported fetal cell transplants for Huntington’s, but the results have been mixed. Dr. Deane “Skip” Jacques of Good Samaritan Hospital in Los Angeles and his colleagues have performed the surgery on more than 20 patients with some reported success.

But Jacques said Wednesday that the gains in function were mainly a reduction in chorea and might have been the result of trauma to the brain from the surgery rather than from integration of the implanted cells.

Dr. Robert Hauser and his colleagues at the University of South Florida in Tampa also have been performing the procedure. Their results have not yet been published, but he said Wednesday that his first six patients followed for at least a year show “statistically significant improvement in motor function.”

With respect to their ability to function in day-to-day life, he said, “We didn’t see improvement, but we didn’t see a worsening either.”

The French scientists are not sure why their results are more promising than previous work. However, the new study is viewed as more definitive than previous ones because the researchers followed the patients for at least two years before the procedure, and thus had a very good indication of the progression of the disease. They also followed them carefully for two years afterward.

In the study, Dr. Marc Peschanski and his colleagues at INSERM, the French equivalent of the U.S. National Institutes of Health, treated five patients with advanced Huntington’s disease. Cells initially were implanted on one side of the brain and then, several months later, on the other side.

Two years after the operations, three of the five patients have improved significantly and have resumed many activities that were not previously possible, such as cycling, mowing the lawn, swimming and playing guitar.

One patient improved initially, then regressed after losing the implanted cells after a brain hemorrhage. The graft did not take in the fifth patient.

“We now have the idea that it is possible to change the progression of Huntington’s disease, which up to now has not been done,” Peschanski told Reuters on Wednesday.

“These new data are important because they provide the first evidence that . . . grafts of tissue taken from human [fetuses] can survive and produce measurable functional improvement in patients with Huntington’s disease,” wrote Dr. Olle Lindvall and Dr. Anders Bjorklund of Lund University in Sweden in an accompanying commentary released on the Web site.

Ross and others cautioned, however, that the number of people treated was very small and that the improvements could conceivably have been produced by either the trauma of the surgery or the use of immunosuppressive drugs.

Peschanski and his team plan to test the procedure on 60 patients at six centers in France and Belgium.

The use of human fetal tissues in such transplants has been very controversial and has limited research. U.S. scientists using federal funds were prohibited from working with such tissues until recently.

Last month, a furor erupted in England when it was revealed that researchers at two universities had implanted fetal cells in four Huntington’s patients--the first time such a procedure had been performed in that country in more than a decade.

But a recent flurry of research has shown--at least in animals--that stem cells from many sites throughout the body can be induced to turn into viable neural cells. If these stem cells could be shown to be as effective as fetal cells, it would greatly increase the supply of tissue available for transplants and would eliminate the need for immunosuppressive drugs.