RE: Performance enhancement with selegiline

From: ct (tilley314@attbi.com)
Date: Thu Feb 06 2003 - 21:06:41 MST

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    At 02:28 PM 2/6/2003 -0500, you wrote:
    >gts wrote:
    > > As stated in the following abstract, from DATATOP, "The study found
    > > that deprenyl [selegiline] treatment almost halved the risk of
    > > reaching a stage of Parkinsonism at which the start of levodopa
    > > treatment becomes imperative for lessening disability."
    > > That looks like potent neuroprotection to me.
    >
    >### It isn't. DATATOP found a *delay* in reaching the levodopa-requiring
    >level of symptomatology, not a reduction in total risk. At the same time,
    >there was no delay in time to dyskinesias on levodopa, and no delay of
    >death. In other words, patients treated with selegiline had the same or
    >higher level of disability as patients on levodopa, levodopa became equally
    >ineffective at the same time, and they died at the same rate. The delay to
    >levodopa is strictly due to the symptomatic effect of selegiline
    >
    >As background: there was once a hypothesis that levodopa accelerates the
    >attrition of dopaminergic neurons, and that levodopa-sparing therapy would
    >delay the onset of dyskinesias which usually develop after about 5-7 years
    >on levodopa, and perhaps prolong survival. A nice hypothesis, but not true -
    >substituting dopa-agonists or selegiline for levodopa in initial treatment
    >does not delay the onset of dyskinesia. ...
    >Rafal
    ==========================================================
    February 6, 2003
    Parkinson's disease: gold standard drug causes heart problems

    Research has shown that levodopa can increase the risk of heart disease in
    Parkinson's patients.
    January 30, 2003 3:58 PM GMT (Datamonitor) - A study published in the Archives
    of Neurology suggests a link between levodopa and increased homocysteine
    levels. This new evidence of adverse side effects will increase the demand for
    treatments that can delay the need for levodopa. Competition will be strong in
    the $2 billion market and Pharmacia and GSK are leading the way with their
    dopamine agonists Mirapex and Requip respectively.

    People with Parkinson's disease (PD) who take the drug levodopa appear to have
    a higher than average risk of heart disease, according to researchers at the
    University of Texas Southwestern Medical Center in Dallas.
    However, researchers stress it is not clear whether levodopa itself raises
    heart disease risks. Experts believe these preliminary findings "raise certain
    concerns" about the safety of levodopa, but are not meant to discourage people
    from taking the drug.
    PD affects over 560,000 people in the US. It is a progressive, degenerative
    condition of the central nervous system, characterized by symptoms such as
    tremor, rigidity, slowness of movement and postural instability. Levodopa
    works
    by replacing levels of the neurotransmitter dopamine in the brain, although
    continued use is associated with undesirable movement side effects known as
    dyskinesias. Moreover, the treatment cannot slow disease progression and works
    only to alleviate the symptoms.
    After experiencing a relatively static five years, the PD market is set to
    grow
    with the recent emphasis on the dopamine agonist class of drugs, which are now
    recommended as first-line monotherapy. The leading players, GlaxoSmithKline
    and
    Pharmacia, will drive this growth with ReQuip (ropinirole) and Mirapex
    (pramipexole) respectively.
    The market is also set to expand with the emergence of revolutionary
    combination drug strategies that aim to reduce levodopa induced motor
    fluctuations and dyskinesias, as well as neuroprotective therapies that delay
    disease progression.
    Levodopa remains the gold standard treatment of PD, despite being over 30
    years
    old and the emergence of new drug classes. It is now highly generacized,
    although controlled release versions of Roche's Madopar and BMS-DuPont's
    Sinemet are popular levodopa therapies in Europe and US respectively.
    Even so, the high volume of sales means the market for levodopa therapies is
    worth over a billion dollars. This new evidence to suggest a heightened
    risk of
    heart disease will increase the need for therapies that can further delay
    levodopa treatment.
    ==========================================================



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