Implanting dopamine generators in brain cells improves Parkinson's in monkeys

May 17 2007

Implanting dopamine generators (dopaminergics) in brain cells has produced improvement in the symptoms in Parkinson's, according to the results of tests carried out with monkeys by the Navarra University Hospital, led by Dr Mar'a Rosario Luquin Piudo, neurologist at the Hospital and at the other Navarra University-based medical centre, CIMA (the Research Centre for Applied Medicine).

The results have been published in the latest issue of the British scientific journal specialising in Neurology, Brain , and have corroborated the conclusions of a previous study, published in 1999 by the same research team in the specialist journal, Neuron . The first name amongst the contributors is that of the researcher Waldy San Sebasti'n.

On this occasion the research was extended to a greater number of non- human primates and for a longer period of time. The procedure involved implanting cell fragments extracted from the carotid body in the striate area of the brain. The carotid body is a small structure located at the bifurcation of the carotid artery, at the level of the neck. Its function is to control the rhythm of respiration and the cardiac frequency through releasing dopamine in situations of low oxygen level in the blood. After the implantation of the cellular aggregates of the carotid body into the striate area of the brain, the improvement in movement in monkeys with Parkinson's and which had received transplants was demonstrated to last for at least a year.

The research team concluded that the mechanism by which the implants in the striate area of the brain of dopamine-generating cells manage to ameliorate Parkinson's appears to be related to the capacity of these cells to release substances (trophic factors) that induce an increase of the dopaminergic cells (that usually exist in the normal brain but in lower quantities). Amongst these trophic factors is the GNDF (Glial Cell-derived Neurotrophic Factor).

Cells extracted from the carotid body have been used as a source for dopaminergic cells in the treatment of Parkinson's disease in animal experiments and in humans. The advantage of this cell type with respect to others is the possibility of carrying out autoimplants, thus avoiding tissue rejection or immunosupressor treatment.

Research

Research was undertaken with monkeys who had Parkinson's induced by the administration of a neurotoxin (MPTP) and which were subsequently injected into the striate area of the brain with fragments from the carotid body of the same animal This region of the brain where the fragments from the carotid body are implanted is the area where dopamine from the dopaminergic neurones is released from the black substance. As is known, Parkinson's disease is produced as a result of the loss of 50% of the cells of the black substance (the brain stem structure) that manufactures dopamine and sends out projections to the striate area.

In order to implant dopaminergic cells in the brain, it is necessary to effect a trepanation through which the fragments from the carotid are injected into the striate area of the animal's brain. This work shows that the number of striate dopaminergic neurones that the striate area of the brain usually contains undergoes an additional increase after the implantation of these cell aggregates. Moreover, this increase in the number of dopaminergic cells appears to be responsible for the improvement of the illness in animals studied by the Navarra University Hospital and CIMA researchers, given that, this was not observed in those individuals receiving injections of saline serum instead of the cellular aggregates.

The fact that the injection into the striate area of neurotrophic factors (those that favour cell growth), such as GDNF, also causes a significant increase in dopaminergic neurones in this region of the brain indicates that the beneficial effect produced by the implant of cellular aggregates is probably due to the action of the GNDF neurotrophic factor containing the cells of the implanted carotid body. In this manner, the GDNF released to the striate area will increase the number of intrinsic dopaminergic cells and these, in turn, on releasing dopamine, will result in an improvement in the condition of Parkinson's.