Ole Isacson and Francesca Cicchetti
Ole Isacson (left) and Francesca Cicchetti check the status of fetal cells implanted in the brain of a Huntington’s disease patient. Groups of these cells appear as red spots in the horizontal brain structures shown at the top of the diagram. The implants survived the disease process and grew to normal adult brain cells. (Staff photo by Kris Snibbe)

Cells from fetuses implanted in the brains of a dozen people with Huntington’s disease improved the ability of nine of them to control their movements and has, perhaps, postponed their deaths.

Huntington’s is an incurable disorder that strikes people in middle age, causing jerky involuntary movements and progressive dementia. Those who will get the malady can be identified by genetic screening, but many people shun the test because no cure exists. This frustrating situation has driven researchers to transplant cells from aborted fetuses into patients’ brains to replace dead cells and stop or reverse the progressive deterioration.

Surgeons at the University of South Florida in Tampa transplanted cells from 9-week-old fetuses into the brains of seven people since 1998. After one year, four of the patients showed a 20 percent improvement on tests of motion, balance, and speech, according to neurologist Robert Hauser. Recipients of three out of five such transplants done in France show similar improvement.

The disease, which affects about 30,000 Americans, “progresses at a rate of 10-15 percent a year,” notes Thomas Freeman, who led the Florida effort. “We have stopped such progress and six patients now show some improvement.”

The seventh, a 54-year-old man, died of a heart attack unrelated to the transplant. An examination of his brain revealed that the fetal cells were not killed by the disease and had, in fact, developed into adult cells that connected with undamaged brain cells.

“This is the first demonstration that such transplanted cells can survive,” says Francesca Cicchetti, a postdoctoral research fellow at McLean Hospital in Belmont, Mass., an affiliate of Harvard Medical School.

“Everyone said that cells put into a degenerating brain would quickly die,” notes Ole Isacson, director of McLean’s Neuroregeneration Laboratory. “They actually stayed alive and developed into normal adult cell types.”

“Further development of this transplantation methodology … may provide hope for functional brain repair in the treatment of Huntington’s disease,” according to Freeman.

“The average age of onset for Huntington’s is around 45 years of age,” Isacson adds. “The optimal treatment would be total prevention, but that may not be possible for a long time, if at all. However, we may be able replace brain cells before any symptoms appear. Since we can determine who will get the disease, we might be able to give people who carry the Huntington’s gene the choice of replacing cells in the most vulnerable regions of the brain.”


Parkinson’s patients improved

Fetal cells have also been transplanted into the brains of people with Parkinson’s disease, a progressive malady that causes trembling, rigidity, slowed movements, and a shuffling gait. Former U.S. Attorney General Janet Reno and ex-boxer Muhammad Ali suffer from it.

“About 150 Parkinson’s patients worldwide have received fetal cell transplants,” says Isacson, who pioneered the technique. “After 10 years, some of them no longer take medications and are very functional.” The transplants work best for patients younger than 60 years, according to J. William Langston, president of the Parkinson’s Institute.

Not all transplantees do well, however. Some were not helped at all and some got worse. “There are different ways to do the transplants,” Isacson points out, “and different procedures produce different results.”

Huntington’s disease is much more complex than Parkinson’s, Isacson says, because it affects a more diffuse area of the brain. “Huntington’s involves almost the entire brain, while Parkinson’s occurs in a small area,” Freeman explains.

One problem with treating both diseases involves the lack of fetal cells. Cells must be at the right level of development for transplantation, and it’s not always possible to coordinate abortions with transplants. Even in places like Sweden, where abortion has been legal for many years, this is a problem. Political opposition in the United States makes the situation more difficult.

Using stem cells might provide a solution. Such cells can be collected from the unused embryos of in vitro fertilization. Stem cells are in an earlier stage of development than the fetal cells used in brain transplants, so they must be grown in lab dishes to develop the right characteristics.


Making better moves

To do the transplants, neurosurgeons carefully drill a hole in the person’s skull, then fetal cells are injected into several areas of the brain. The brain lacks sensory fibers so no pain is felt. Local anesthesia is given for the drilling, but the patient remains awake during the procedure.

Examination of the brain of the Huntington’s patient who died proved that injected cells can survive toxic conditions and grow to become normal cells. “We see connections that have grown from these implanted cells to other areas of the brain,” notes Cicchetti. “What we do not know for sure is whether the transplanted cells actually have taken over functions once performed by now dead cells, that is, if they are helping the patient control his or her movements. Since the implanted cells thrived for a year and half, that may have happened, but we have no irrefutable evidence that it did.”

“However, such long survival is good news not just for fetal-cell transplantation but for using stem cells,” adds Isacson.

Most of the patients think it’s good news, too. On standard tests that measured their balance, twisting and turning movements, fine motions, walking, and speech, four of the seven who underwent transplants in Florida showed a 20 percent improvement after surgery. Two others exhibited some progress, and the man who died was doing better while he lived.

“One patient showed less involuntary twisting and turning only a few days after the operation,” Hauser noted. “We hope this was due to the implant, but we don’t know.”

Two patients suffered blood clots in the space between the top of their brains and the inside of their skulls. “Huntington’s patients suffer loss of spinal fluid, causing their brain to shrink and this space to expand,” explains Thomas Freeman. “That person got worse at first, but now is almost back to normal.”

French researchers reported in the medical journal Lancet that they found improvements in daily living activities and reduction in the severity of rapid, jerky movements in three out of five patients. Cognition and movement deteriorated in the other two transplantees. All received cells from 7- to-9-week-old fetuses

“We’ve proved that the transplants survive,” Freeman says. “To determine how effective they are over a longer term, we need to do more transplants. We also need to do them at earlier stages of the disease.”

The French group is currently organizing to do more transplants at a number of different medical centers, according to Marc Peschanski, leader of the team.

“I truly believe that such new efforts will eventually lead to less suffering and will delay the deaths of patients until a cure is found,” says Isacson.