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


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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/

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