"Ask Dr. Jankovic"

Director, Parkinson's Disease Center and Movement Disorders Clinic,

Department of Neurology, Baylor College of Medicine

Q: Can brain grafts cure Parkinson’s disease?

A: The implantation of nerve cells (neurons) into the brains of parkinsonian animals or patients (brain grafts) is not a novel idea. Initial experiments, performed over a 20 year ago, showed that parkinsonian rats improved following implantation of neurons obtained from the fetal midbrain, a brain area which during embryonic development gives rise to dopamine producing neurons. Since then, it has been clearly demonstrated that fetal dopamine producing cells transplanted into an adult brain survive and correct motor deficiencies in animal models of Parkinson’s disease and in parkinsonian patients. Because of ethical and logistic issues, human fetal neuronal tissue is difficult to obtain and, therefore, scientists have searched for other sources of dopamine producing cells. In 1989 we reported the experience at Baylor’s Parkinson’s Disease Center with transplants of tissue obtained from the patient’s own adrenal gland. Although some patients clearly improved the benefit was not sustained, probably because the grafted neurons did not survive. Using tissue derived from a fetus rather than an adult increases the chances of survival in the host brain. More than two hundred grafts of human fetal midbrain have been performed in patients with Parkinson’s disease, utilizing a variety of cell preparations and neurosurgical methods to deliver the fetal cells into the part of the brain affected by Parkinson’s disease (the striatum). These refinements in delivery techniques have resulted in more substantial and sustained clinical improvement, permitting a marked reduction or even discontinuation of antiparkinsonian medications. The research studies have demonstrated that human fetal brain grafts survive in the brains of patients with Parkinson’s disease. The use of human fetal neurons for widespread treatment of Parkinson's disease, however, is limited because of ethical, infectious and practical concerns. Therefore, cells harvested from a brain of a pig fetus (porcine grafts) provide a virtually unlimited source of dopaminergic cells which are physiologically similar to human midbrain cells. Encouraged by the favorable results from the initial pilot study involving twelve patients implanted with porcine brain neurons, we at Baylor’s Parkinson’s Disease Center have decided to participate in a multicenter trial designed to study the safety and efficacy of porcine transplants in patients with moderately advanced Parkinson’s disease. In order to minimize immunologic rejection of the foreign graft by the patient’s immunologic system the pig cells are treated with a special antibody. This has been shown to prolong survival of the graft and presumably provide more sustained benefits to the patients.

One of the most exciting areas of brain graft research is the emergence of a new strategy for brain repair involving stem cells. These very primitive cells are unique in that they can be grown in a test tube or a culture dish and by manipulating their environment (culture) they can be made to differentiate (specialize) into any type of cell, including dopamine producing nerve cells. This discovery has completely changed our thinking about the brain which until now was thought to consist of nerve cells (and supporting cells called glia) that do not divide. When these progenitor stem cells are injected into an intact striatum (the portion of the brain affected by Parkinson’s disease) they acquire the characteristics of striatal nerve cells. These studies suggest the possibility that the brain cells that have been lost as a result of Parkinson’s disease can be replaced. The use of neural progenitor (stem) cells in repair and as a source of trophic factors is currently being investigated in a number of laboratories around the world, but it will take several years before this technology can be applied in humans. Nevertheless, these new advances offer the promise that eventually we will be able not only treat the symptoms of Parkinson’s disease but, more importantly, repair the damage and slow or prevent the progression of the disease.