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hi all as one parky who has been prescribed levodopa-carbidopa and selegiline since diagnosis day one = november 1988 = 15 years = 5,000 + days, there are some things about this report which sit uneasy in me levodopa and its 'long duration response' (which has only recently come to light despite its having been prescribed for parkies and pronounced the PD gold standard for over 25 years) seems to me to have more implications than just 'promising therapeutic opportunities' and the hundreds of millions of dollars supposedly estimated to produce them if i have learned anything about levodopa and pd and the pd patient community over the past 15 years it is that there is a lot to learn and a lot of ignorance to dispell the terminology 'long duration response' brings up to my mind at least questions of long term overdose and side effects of levodopa many of which psychosis depression anxiety dyskinesia have been documented as being more disabling to the pd patient than pd polypharmacy is dangerous and has become only more so with the recent proliferation of new pd drugs and the lack of information about their dosing standards and their interactions joe bruckbauer, karen bardo, greg leeman, and countless others are described in my website as having been misguided and mismanaged as to their pd med regimens to the point of illness and even death the list of potential new agents is 'daunting' indeed but not nearly as daunting to this parky at least as the lack of information about the old agents janet ------------------------------------------------------- Neuroprotection in Parkinson's disease: Clinical trials. Advances in our understanding of the cause and pathogenesis of Parkinson's disease (PD) have permitted the rational selection of putative neuroprotective agents for study in PD. However, the list of agents that might provide neuroprotective effects derived from laboratory studies is daunting, and we face the challenge of determining which agents to bring to the clinic and how to find the resources (patients and funds) to properly study so many promising therapeutic opportunities. Appropriate outcome variables that are not confounded by any symptomatic effect of the drug and are acceptable to clinicians and regulatory authorities also remain to be defined. The first clinical trials designed to test the capacity of putative neuroprotective agents to alter the natural history of PD have now been performed and illustrate some of these problems. The DATATOP (Deprenyl and Tocopherol Antioxidant Therapy of PD) study used the time to reach a disease milestone in untreated PD patients (ie, need for levodopa) as the primary end point. However, interpretation of results was confounded by the drug's symptomatic effect. The SINDEPAR (Sinemet-Deprenyl-Parlodel) study used the change in motor score between initial visit and final visit after washout of all study medications as the primary end point. However, here too there were concerns about confounding symptomatic effects, because antiparkinsonian medications have now been shown to have a long duration response that can persist for weeks and perhaps even months after withdrawal. More recent studies have used surrogate markers of the integrity of nigrostriatal function such as striatal uptake of fluorodopa on positron emission tomography (PET) or beta-CIT-on single-photon emission computerized tomography (SPECT) as primary outcome measures. However, it has not yet been confirmed that striatal uptake of these isotopes does in fact correlate with the remaining number of dopamine neurons or terminals, and the possibility of a confounding pharmacological effect has not yet been completely excluded. To date, no drug has been established to have a neuroprotective effect in PD, and none has been approved for a neuroprotective indication. Furthermore, regulatory agencies have not yet agreed that any of the outcome measures currently used will be acceptable for approval of a new drug. Resolution of these issues is of critical importance to convince pharmaceutical companies to expend the hundreds of millions of dollars necessary to bring a new drug to market. Drugs that already have been approved in PD for their symptomatic effects, such as dopamine agonists or propargylamines (eg, selegiline), offer the best opportunity for establishing that a drug is neuroprotective in PD in the immediate future, but herein also lies the difficulty of establishing that any benefits observed are not solely because of the drug's symptomatic properties. Currently, this will most likely entail demonstrating that the drug provides benefit for PD patients for both imaging and clinical markers of disease progression. Ann Neurol 2003;53 (suppl 3)S87-S99 Stocchi F, Olanow CW. University La Sapienza, Rome, Italy. PMID: 12666101 janet paterson: an akinetic rigid subtype, albeit primarily perky, parky pd: 56-41-37 cd: 56-44-43 tel: 613-256-8340 email: [log in to unmask] my newsletter: http://groups.yahoo.com/group/newvoicenews/ my website: http://www.geocities.com/janet313/ ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn