Q:How successful are some of the new therapies for Parkinson’s disease? I’ve just heard that doctors are experimenting with transplanting fetal brain tissue in patients with Parkinson’s. What are the side effects of the drugs? Are there any other wa
A:Typically, doctors aren’t happy unless they’re engaged in major life-
and-death solutions. In Parkinson’s, a group of cells in the brain degenerates. These cells are responsible for producing dopamine, a brain chemical which transmits instructions from the brain to nerves controlling movement. As the cells degenerate and dopamine levels fall, so movement becomes more involuntary and difficult. Attempts have been tried by many international research teams to implant tissue containing dopamine neurons in the brains of patients with Parkinson’s disease, demonstrating moderate improvement in studies reported in 1987. However, subsequent studies showed that the grafted material didn’t survive well in humans, although it did so in animals.
Late last month, scientists were aflutter with the publication of a study of the successful implantation of dopamine producing cells from aborted fetuses in a 59-year-old man with Parkinson’s disease (New Eng J of Med, April 27, 1995). The man received implants from seven fetal donors during two operations (48 fetal grafts in all). Between one and three months later, clinical improvement in motor behaviour was noted and continued up to 15 months. Advanced scanning techniques showed not only that the graft had survived but also that regions of the brain had new cells. Although the patient died from a pulmonary blood clot 18 months after the operation (no one bothered to ask if there might be a connection), the pathology report showed that the grafts had survived and that brain tissue had grown normally.
Besides our ignorance over whether grafts can last longer or prove safe, we also don’t know if the grafts can prevent the progression of the disease or if they will eventually succumb as well. It’s also important to note that although patients with transplants were able to reduce their medication, thus far, no patient had been able to come off it entirely. This all signals that surgeons are very much at the drawing board stage with this experimental operation.
Besides messing around with fetal tissue (with its ethical implications), researchers at King’s College in London have been experimenting with such solutions as engineering the herpes virus to make dopamine, because of its ability to last indefinitely. At the moment, scientists have a long way to go, as the engineered virus is potentially fatal.
The orthodox possibilities for Parkinson’s victims are no less grim. Because dopamine derives from L-dopa, an amino acid, the standard treatment is to give patients L-dopa, or levadopa, which tends to restore dopamine levels to normal and lessens parkinsonian symptoms. However, this improvement also has its price; patients on L-dopa develop nausea or vomiting, postural hypotension (fainting on getting up), sweating attacks, psychotic symptoms like hallucinations, delusions and confusion, and, most ironically, motor difficulties and involuntary movements the very thing they’re being treated for! For all these reasons, the latest advice is that levodopa be delayed until a patient is over 70 (BMJ, March 4, 1995). (See drug of the Month, p 7.)
A popular choice for early Parkinson’s are the anticholinergic drugs (benzhexol and orphenadrine). These drugs, which are more mild than L-dopa, are more effective for tremor, rather than other symptoms, although patients can worsen considerably if the drugs are suddenly withdrawn. The side effects include blurred vision, dry mouth, constipation, retention of urine and possibly worsening of some of the movement disorders (BMJ, March 4, 1995).
The third main category are dopamine agonists (bromocriptine and pergolide), which act on the dopamine receptors of the brain. They can prevent nausea (although initially they cause it), but also have worse psychotic side effects than L-dopa and cause sudden lowering of blood pressure, which poses a considerable risk of hip fracture in a patient who is unstable at the best of times.
Selegiline is one of a number of enzymes which help to metabolize L-dopa and have it last longer, although, again, it makes psychiatric and movement side effects worse. Risperidone has been suggested as a drug to take care of some of the psychiatric side effects of L-dopa (The Lancet, May 28, 1994).
Given this line-up of debatable options, nutritional doctors like WDDTY panel member Melvyn Werbach offer a better approach. He notes that since L-dopa must compete with other amino acids for transport from the blood to the brain, it makes sense to limit protein, from which amino acids are derived, to lessen the competition. In several studies, he says, protein restriction has made L-dopa more effective and lessened the “on-off” effect, where people do better at certain times of the day.
Dr Werbach suggests that you restrict your daily intake of protein to 0.12 oz per lb of body weight, and serve 90 per cent of this with your evening meal.
Other suggestions include supplementing with folic acid (a deficiency can cause Parkinson’s disease), niacin, B6, vitamin C, vitamin E, iron,
omega-6 fatty acids (and watching for excessive intake of manganese).
L-tryptophan, another amino acid, prevents some of the side effects of L-dopa, or you can use L-tyrosine as a substitute for L-dopa when side effects are severe.
Also check for mercury or other industrial heavy-metal poisoning, which has been implicated in Parkinson’s disease (Movement Disorders, 1993, 8(1): 87-92).