Since there is a lot going around about the possibility of MJFox "acting" and Rush being as ass about it I figured I would lend some professional knowledge about the current medication regime. Go below the fold to learn about acute and graual loss of effectiveness.
The goal with currently available drugs is simple to improve the patient's ability to carry out activities of daily life. Given the neurochemical basis for parkinsonism- too little striatal dopamine and too much ACh- the approach to treatment is obvious: Give drugs that can restore the functional balance between dopamine and ACh.
Levodopa is the most effective treatment for PD. However the beneficial effects diminish in long term use. For patients with advanced disease Levodopa is THE drug of choice. If levodopa by itself is inadequate, it can be combined with a dopamine agonist, amantadine, or a COMT inhibitor.
ACUTE LOSS EFFECT: Acute loss of effect occurs in two patterns: gradual loss and abrupt loss. Gradual loss develops near the end of the dosing interval, and simply indicates that plasma drug levels have declined to a subtherapeutic value. Abrupt loss can occur at any time during the dosing interval- even when drug levels are high. Its like an on-off phenomena. The "off" time may last minutes to hours. Over the course of treatment off periods are likely to increase in both intensity and frequency.
So pretty much Levodopa wears off eventually. There are some other medications that can be combined and dosing therapy can be switched up but it WILL stop working. So Rush is partially correct. MJFox is off his medication in the sense that taking it is no longer really having much of an effect. That is a harsh, harsh reality for PD patients. What are their other options as of now?
Potential options include pallidotomy, which is a neuro surgical procedure for destroying a region of the globus pallidus. Deep brain stimulation, which is electrical stimulation of specific brain areas-- improves some symptoms for a short time. The last option?????
Cell implants. The objective is to replace degenerated dopaminergic neurons. As of now benefits are modest. In 1995 (who was president then?) researchers finally obtained definitive proof that transplanting fetal dopaminergic neurons into the brain can benefit a patient with PD. In this case study, the patient had severe parkinsonism that would no longer respond to drugs. Following the transplant, symptoms steadily improved over 3 months, eventually allowing the patient to perform all activities of daily living without assistance. The improvements were sustained for 15 months, at which time the patient died of a massive pulmonary embolism unrelated to the transplant. Autopsy revealed that the grafts not only took but had become seamlessly integrated into the surrounding tissue.
All info presented is from published works by Richard Lehne, which include research on the topic.