From: Rafal Smigrodzki (rafal@smigrodzki.org)
Date: Mon Feb 17 2003 - 09:06:16 MST
owner-extropians@extropy.org wrote:
> Rafal wrote:
>
> [gts wrote]
>>> Rafal hangs his hat on a single study in which selegiline (deprenyl)
>>> slowed the progression of Parkinson's disease symptoms (a remarkable
>>> result!) but in which the drug was not found to actually extend the
>>> life of those same Parkinson's patients.
>>
>> ### I explained before but can do it again: selegiline did not slow
>> the progression of symptoms, merely symptomatically delayed the time
>> to levodopa, as shown by the loss of efficacy during washout.
>
> I stand by my words. Selegiline delayed the time to which symptoms
> become severe enough to require treatment with levodopa. That is
> "slowing the progression of Parkinson's disease symptoms" by anyone's
> definition, Rafal.
### No it isn't. The symptoms appeared at the same rate, but were delayed. I
was referring to the absence of any influence on the progression of the
underlying disease process. Slowing the progression of a neurodegenerative
disorder is when a treatment slows down the loss of neurons. It can be
postulated when even after the withdrawal of the treatment (the washout),
there is some improvement over placebo.
If a treatment produces strictly symptomatic relief, it covers up the loss
of neurons by e.g. activating remaining neurons or other compensatory
mechanisms. However, once the treatment is withdrawn, the underlying loss is
again fully manifested, and the patient returns to the same state as the
placebo patient. This is exactly what happened with DATATOP patients during
washout.
Additionally, there are more supporting data for this explanation - the time
to dyskinesias. Dyskinesias develop during treatment with levodopa when the
number of remaining dopaminergic neurons becomes critically low. It is a
marker of progression of the disease, independent (probably) of any
treatment. In DATATOP, both selegiline and placebo patients developed the
dyskinesias at the same absolute time since the onset of the disease,
implying (but not proving) that there was no slowing of the process.
The only difference was a delay in the development of gait freezing, which
could indicate a slowing of neuronal loss in one of the populations involved
in gait ignition (premotor cortex?). However, this has a very limited
clinical significance.
--------------------------
>
> The only disappointing thing about that particular study is that these
> patients did not also live longer than those who were treated with
> levodopa alone. A plethora of research outside of that study supports
> a neuroprotective role for selegiline, and in fact that study did not
> actually disprove such a role.
### It did disprove any clinically significant neuroprotection. See above.
Rafal
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