Julie’s

Ask Dr. Beristain

Questions & Answers with

Dr. Xabier Beristain, Neurology Indiana

863-2095

What can you tell us about the “Parkinson’s patch”?

Even though there is a newly FDA-approved patch = to treat PD there have been other attempts to deliver PD medication through the skin. This includes a recent small preliminary study to deliver levodopa in this fashion. The main objective of this study was to assess how, how much = and how steadily levodopa got into the system of healthy volunteers using a skin patch of levodopa. Should this approach work, it would potentially offer a very useful alternative to oral levodopa. Unfortunately this is a pilot study and it will take further stud= ies to see if this approach is effective in PD patients.

On the other hand, “the patch” that = people are likely referring to is the rotigotine transdermal system. It has been recently approved by the FDA and will be known as Neupro®. Rotigotine i= s a non-ergolinic dopamine agonist that is designed to continuously be released from the patch over a 24-hour period. This will in theory allow for a more steady delivery of medication and hopefully minimize some of the side effec= ts that are common to other dopamine agonists (e.g.: pramipexole-Mirapex®-= and ropinirole -Requip®) such as hallucinations, lightheadedness, sleepines= s or nausea among others, although it may cause skin reactions where the patch is applied. This new medication is supposed to be available at the pharmacies = in early July 2007.
What is Parkinson-plus?

Parkinson-plus or parkinsonism is the generic term used to describe a family of disorders that share some features with PD but, also have other associated symptoms that a= re uncommon or do not happen at all in PD (i.e.: the “plus” of Parkinson-plus). Early on it can be quite difficult to distinguish Parkinson-plus from true PD as there is significant overlap of signs and symptoms but over time it becomes clear since Parkinson-plus conditions do = not behave in the same way expected of classic PD. Among Parkinson-plus disorde= rs we may encounter progressive supranuclear palsy (PSP), multiple system atro= phy (MSA), corticobasal degeneration (CBD), Lewy body disease (LBD) and some others. The prognosis of Parkinson-plus syndromes is more somber that of classic PD as these conditions tend to respond less robustly or not at all = to anti-PD medications, progress faster and may cause significant problems with early falls (e.g.: PSP), significant drop in blood pressure and fainting sp= ells (e.g.: MSA), early dementia with significant visual hallucinations (e.g.: L= BD) or major inability to use limbs despite good strength (e.g.; CBD). As the diagnosis of these conditions is clinical it may take months to years to ob= tain the correct diagnosis. It is = not uncommon to be incorrectly labeled with PD for a while, even at reputable centers. According to studies done at Baylor, a very reputable Movement Disorder clinic, condition such as PSP may be present in as many as 6% of t= heir patients. However, this could= be an overestimation due to the possibility of them seeing more “difficult patients”, many of whom may end up having a Parkinson-plus condition.=

What causes PD?

For year PD was thoug= ht to be a sporadic disease caused by some sort of environmental exposure. However in the last decade several genes that play a role in the origin of PD were and still are being discovered. And probably for most of PD patients it is a di= sease caused by the interactions of environment and genetics. On the other hand f= or a few kindred around the World is a classical genetic disease. Genes do probable play a more significant role in early and juvenile onset PD if compared to the classical late-onset disease. Patients with PD when asked about other relatives with = PD may report so in about 10 to 15% of the times. Regarding what environmental exposures are responsible, the list is probably long and incomplete, includ= ing environmental toxins such as pesticides, infections and trauma. On the other hand some studies have shown that some “exposures” could decrea= se the risk, such as coffee drinking and smoking among others.

Several genes have be= en identified including the alpha-synuclein, Parkin, LRRK-2, and PINK-1gene am= ong others. For most of PD patients, testing for some of these genes is not cost-effective as the yield is low and may not change management. They prob= ably do play a more important role in the evaluation of early PD.

Does Isradipine (Dynacirc®) help PD?

Researchers at Northwestern Univers= ity in Chicago, IL have recently published a research = paper on the effect of Isradipine in mice and it’s potential role to protect dopamine cells and slow down PD. Isradipine slowed the disease process and destruction of the dopamine-producing neurons in the mouse model and this m= ight have implications for humans. In young mice, do= pamine cells use sodium channels to send signals, but in older mice they rely more= on a certain kind of calcium channel. By blocking the calcium signaling with isradipine the researchers try to “force” dopamine cells to rel= ay more in sodium channels as calcium accumulation inside the cells may damage them and cause degeneration and eventual cell death. The researchers implan= ted a time-release capsule of isradipine beneath the skin of young adult mice a= nd after one week on this regimen they were exposed to MPTP, a selective toxin= of dopamine cells used in animal models of PD. Several weeks after starting israd= ipine the mice exposed to MPTP had no sign of PD-like symptoms but the ones not receiving the agent were parkinsonian. Even though these results are interesting and exciting we should be skeptical that a cure is around the corner; selegiline, for instance, was shown to protect animals from the tox= ic effects of MPTP but the human trials never showed unquestionable evidence of neuroprotection. In addition this isradipine study is in healthy mice pretreated with the drug and before being exposed to MPTP. We do not know w= hat would happen if we applied this compound in mice after being exposed to MPTP and see if it would help PD-like symptoms. More studies are needed to see if this initial promise holds by performing more animal studies before any hum= an PD trials are conducted.

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