The alternative result GDNF
 

GDNF. Where now? – Jon Stamford

What should we believe?

Jon's article is well worth a read. If you want to look further, it is useful to see the data in the paper [1] that includes the results for the 40 - 80 week period. The first period, 0 - 40 week, was double blinded, placebo controlled. The second period, 40 - 80 week was open label, with the original treatment group continuing as before and the original placebo group now also taking the treatment.

This GDNF trial should become a classic case study of statistical analysis. Every time a read it I come away with a different picture.

The ones that interest me today are:

LEDD mg, GDNF/GDNF, baseline= 1011, week 80= 1071
LEDD mg, Placebo/GDNF, baseline= 954, week 80= 1243

Timed tapping: OFF-state, GDNF/GDNF, baseline= 43.1, week 80= 63.8
Timed tapping: OFF-state, Placebo/GDNF, baseline= 42.4, week 80= 59.1

The increase in the levodopa equivalent daily dose especially in the Placebo/GDNF group is likely, in my opinion, to be a confounding issue.

Reference

[1] "Extended Treatment with Glial Cell Line-Derived Neurotrophic Factor in Parkinson’s Disease"
Alan L. Whonea et al.
Journal of Parkinson's Disease 2019, Corrected Proof
https://content.iospress.com/downloa...se%2Fjpd191576

John

After off meds assessment we were all given sinemet 350MG to bring us on,
Im a 5ft 2 woman what about the 15 stone 6ft man.The on dose should be titrated up to the individual need.
If I had a full English breakfast time to on was 50 minutes a banana was 10 minutes.what you eat effects outcome statistics.Im wrong perhaps but it makes sense to me it an important question

It makes sense to me too.

Although behind a paywall a paper by Zappia et al. [1] states:

"Patients underwent an oral acute LD test with 250 mg of LD".

"In our sample, women were significantly lighter and had a significantly greater area under the curve than men."

That suggests that women get the benefit of more levodopa.

"Moreover, a greater percentage of women showed LD peak-dose dyskinesias compared with men."

That suggests that weight has some pharmacodynamic effect.

Also, I would suggest that as the disease progresses, and dopaminergic cells die off, reducing both the endogenous production and storage of dopamine, the more closely that the pharmacodynamics follow the pharmacokinetics.

Reference:

[1] "Body Weight Influences Pharmacokinetics of Levodopa in Parkinson's Disease
Zappia, Mario et al.
Clinical Neuropharmacology: March-April 2002
Body Weight Influences Pharmacokinetics of Levodopa in Parki... : Clinical Neuropharmacology

John