Regeneration, Part 2

A User's Guide to the Brain: Perception, Attention, and the Four Theaters of the Brain
by John J. Ratey, M.D.

(Page 11 of 12)

The anecdotal evidence is somewhat encouraging. Curt Freed at the University of Colorado says that roughly two-thirds of the patients have improved. Half can abandon their medication altogether while keeping up normal appearance. A study by Olle Lindvall at Lund suggests that remission can last for up to six years.

However, the results remain open to debate, since techniques for doing the transplants have not been standardized. Researchers do not agree on how much fetal tissue to implant, and they do not know how best to scatter the cells in the patient's brain. None of the researchers has much idea what is happening in the third of the patients who do not improve.

Another recent breakthrough has been the parallel work of teams at Johns Hopkins and at the University of Wisconsin who have successfully cultured embryonic stem cells in the laboratory. These cells may someday be able to be harvested for successful transplantation into the brain. We are coming into an age when mature nerve cells can be changed into undifferentiated young neurons in a Petri dish by manipulating the function of their genes, which will allow more rapid progress of this line of research and will get around the ethical issues that have marred its progress thus far.

Meanwhile, researchers are trying the same approach in patients with Huntington's disease, the hereditary disorder that killed Woody Guthrie, which also involves the striatum. Unlike the symptoms of Parkinson's, which can often be checked with a drug called L-dopa (making transplants a treatment of last resort), the symptoms of Huntington's disease cannot be counteracted, and the disease affects intellectual function as well as movement, leading to severe dementia and death.

More positive results are needed before transplantation of fetal nerve cells can be said to be effective. The ethical objections to the use of cells from aborted fetuses persist, too; up to eight fetuses are used for some Parkinson's patients. Legislators have tried to pass laws to ensure that a woman's decision to have an abortion is not influenced by the idea that her fetus's tissue may help a Parkinson's victim, and many states still prohibit fetal-tissue transplants. Clearly, we need new ways for getting immature brain cells that do not involve fetal tissue. Another way around the problem would be to find an animal source of nerve cells.

Fetal pigs are one possibility. One of the problems is that the brain may reject any cells that are not its own, more so if they are not even human. Like pig insulin, which is rejected by diabetic humans much less than beef insulin, pig's brain cells are less likely to be rejected. When transplanted into rats with Parkinson-like traits, pig donor cells can accurately rewire damaged portions of the striatum.

Undifferentiated fetal pig cells have already been implanted in the brains of some Parkinson's patients at the Lahey Hitchcock Medical Center in Burlington, Massachusetts, in hopes that the cells will take on local functions, such as the production of dopamine. The first person to receive such cells was Tony Johnson, a fifty-seven-year-old civil engineer who had endured Parkinson's for twenty-seven years. Six months after a tiny drop of cells was injected into his brain, Johnson's wife told the Boston Globe that her husband's speech and walking were better, though he still needed drugs to control his symptoms.

Researchers at Harvard Medical School have shown that nerve cells from fetal pigs can mature in the human brain, but so far the number of trials has been small. About a dozen Parkinson's and a dozen Huntington's patients have had fetal-pig-cell transplants. Their recovery rate is comparable to that of patients receiving human fetal tissue; over half have regained some of their motor control six months after surgery.

While using pig cells overcomes the ethical questions raised in connection with the use of human fetal tissue, it brings problems of its own, as it carries the risk of transplanting pig diseases. Therefore, a third possibility is being pursued: regenerating replacement cells taken from a patient's own brain.

Recent research has overturned the old neurological dogma that adult brains cannot renew themselves. It used to be thought that neural stem cells (neuroblasts)-which divide to produce nerve cells in the fetal and child brain-shut down in adulthood. But Brent Reynolds and Sam Weiss at Neurospheres, a Canadian biotechnology company, have shown that stem cells may be inactive in adults but are still alive, and might be prompted to create new neurons. They have coerced stem cells in a test tube to churn out new cells by adding "growth factors," molecules that stimulate tissue growth. If this were sustained, cells already in the patient's brain could be triggered, or moved and triggered, to create new neurons to replace the lost brain function.

Scientists at Ontogeny, a company in Cambridge, Massachusetts, are trying to leapfrog this procedure by working with a potent growth-factor protein that, in a Petri dish, can transform stem cells into mature dopamine producers. They have named the protein "sonic hedgehog," after a fast-moving children's video-game character. They are currently implanting it into the brains of mice to see what happens. One of the oldest biotech companies, Amgen, is experimenting with growth factors derived from glial cells, which has been effective in slowing the onslaught of Parkinson-like symptoms in monkeys. Amgen's and Ontogeny's approaches would require regular injections of growth factors into the brain, which means a patient would have to have a hole drilled in his skull and be fitted with a catheter.

It will be some time before efforts to regenerate brain cells become part of established medicine. Meanwhile, for the vast majority of us, who are not debilitated but are coping with everyday problems and with aging, the lesson about brain development is that we have the power to influence our brain's ability to renew itself. The human brain's amazing plasticity enables it to continually rewire and learn-not just through academic study, but through experience, thought, action, and emotion. As with our muscles, we can strengthen our neural pathways with brain exercise. Or we can let them wither. The principle is the same: Use it or lose it!

Excerpted from A User's Guide to the Brain by John J. Ratey, M.D. Copyright © 2002 by John J. Ratey, M.D.. Excerpted by permission of Vintage, a division of Random House, Inc. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.

About the Author

John J. Ratey, M.D., is an associate professor of psychiatry at Harvard Medical School. He has lectured extensively and published many articles on the topic of treating adults with ADD. Dr. Ratey is the author of A User's Guide to the Brain and the co-author of Driven to Distraction. He lives in Cambridge, Massachusetts, where he has a private practice.