Greetings Terry:
I am not a doctor, so my opinions are not medical advice.
You indicate that you were diagnosed with PD at the age
of 30 and are now 40 yrs old . . . clearly you fall into the
category of "Young Onset PD" which is dx from 20 to 40 yrs.
Your question is: "Does Sinemet add to the progression
of the disease?"
Some background first -
It is the deficiency of the chemical dopamine in our PD
brains that is credited with the reason PWP exhibit slowness
of movement (bradykinesia), tremor and rigidity.
Replacement of the dopamine (with its chemical
precursor, levodopa) in the form of Sinemet
(carbidopa/levodopa) is considered to be the most effective
therapy. Levodopa therapy has shown to normalize motor
function, thereby improving the patient's daily living and
reduce the mortality rate of PWP.
Levodopa therapy continues to be effective over many
years and in the majority of patients it does not lose
effectiveness. However, apparently, there are limits . . . a
significant minority of patients complain of a lessening of the
benefits of levodopa therapy after as little as 5 years of
treatment. This is described as the "wearing off"
phenomenon and is addressed by doctors adjusting the
frequency and dosage of levodopa to try to maintain a more
constant level (not necessarily an increased level) of
levodopa in the bloodstream.
Higher levels of levodopa meds do not always treat the
problem. As the total dosage increases for some patients
(instead of the same or smaller dosages at more frequent
intervals) patients develop involuntary twisting or jerking
movements (dyskinesias) . . . why this is so is not clear . . .
but researchers think it is a combination of the progression of
the illness (death of more brain cells) and the effects of
poorly regulated, or chronic intermittent therapy with
levodopa.
The reason why our brain cells are dying is unknown, but
scientists speculate it could be due to higher levels of "free
radicals" in our brains. Free radicals are considered to be
chemically-reactive molecules created by the body's natural
oxidative process. The free radicals are minus an electron
and try to capture an electron from the nearest cell, creating
a cascade effect of electron theft. Antioxidants in our body
are given the task of destroying the free radicals before they
injure a cell's DNA. The most familiar antioxidants are
vitamins C, E and A and minerals such as Selenium and
Zinc.
One source of toxic free radicals in our brain - substantia
nigra - is the normal breakdown of dopamine by the enzyme
monoamine oxidase B (MAO-B), which in turn is blocked by
selegiline (Eldepryl). Therefore, some researchers believe
that selegiline should decrease the free radicals in the brain,
slowing the progression of the disease, but it cannot yet be
proven empirically.
Additionally, enzymes which convert therapeutic levodopa
into dopamine in our brains also produce potentially toxic
oxyradicals (free radicals) which are considered to be harmful
to nerve cells. Researchers have only tested their theories
on cell cultures, which have shown levodopa AND
DOPAMINE both are toxic to nerve cells. The level of harm
is related to the concentration of levodopa or dopamine and
the length of exposure. In other experiments with rats,
researchers were unable to produce damage to nerve cells
by administering levodopa.
Evidence about potential toxicity of levodopa over the long
term is minimal. Reports of long-term or large cumulative
doses of levodopa given to patients who exhibited tremor, but
not necessarily PD, only concluded that there was no
evidence of damage to the substantia nigra.
A reported study (at the Sept. 1997 meeting of the Amer.
Neuro. Ass'n) by Dr. Jankovic, Houston, Texas, found that
YOPD initially responded to levodopa better than PWP who
were dx after 60 yrs, but that they were more likely to
develop long-term levodopa-connected motor complications
such as "wearing off" and dyskinesias.
My situation is that I was dx at 46 yrs and have taken
Sinemet CR 50/200, three times a day for seven years. I
have also taken 5mg of Eldepryl twice a day until 6 months
ago, when I reduced it to 5mg in the morning only, with the
consent of my neuro. He and I had read a 1997 study on
selegiline which found that the neuroprotective effect was
maximized at 20mg for a five day period. I have had fewer
incidences of vivid dreams in the past 6 months.
I have not noticed any "wearing off" or increase in motor
fluctuations over the past 7 years. My usual response to a
single Sinemet CR tablet is that about two hours into each
med I experience peak dose rigidity for about 20 - 30
minutes.
I hope this information helps you. Good luck.
Stephan 53/7
