Aromatic L‐Amino Acid Decarboxylase Gene ... - Cure Parkinson's

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Aromatic L‐Amino Acid Decarboxylase Gene Therapy Enhances Levodopa Response in Parkinson's Disease

Farooqji profile image
6 Replies

Of the 15 Parkinsons participants in the PD‐1101 clinical trial (evaluating

Gene therapy candidate VY‐AADC01), 13 participated in a substudy aimed at determining timing & magnitude of motor response to intravenous levodopa. Results:

onlinelibrary.wiley.com/doi...

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Farooqji
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sharoncrayn profile image
sharoncrayn

Another good find.

"As Parkinson's disease progresses, levodopa treatment loses efficacy, partly through the loss of the endogenous dopamine‐synthesizing enzyme L‐amino acid decarboxylase (AADC). " ...........(the common L-amino acid decarboxylase (AADC) inhibitors are benserazide and carbidopa ... )

This study is Heresy for all those pwp and doctors who think sinemet and similar drugs are the gold standard for PD, but don't understand the "why" of the reality of PD's progression over time in almost all cases. Doubt they will read the study or understand its probable implications.

Too bad.

Sharon

in reply tosharoncrayn

What are the probable implications?

sharoncrayn profile image
sharoncrayn in reply to

An earlier 2019 study (Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease) used putaminal administration of VY‐AADC01 and was tested on supposedly moderately "advanced" PD patients using MR image guided administration to optimize delivery.

It was delivered to the putamen part of the brain, which is generally considered historically less important (but still relevant in PD) to the progression of parkinsons than the substantia nigra and the globus pallidus.

Importantly, this approach avoided earlier problems with an increased risk of intracranial hemorrhage and self-limited headache.

The referenced study in this thread was a sub-study showing that VY-AADC01 improved motor responses to IV administered levodopa.

So, the probable (possible is a better word) implication here is that we should continue and proceed with development of AADC gene therapy which goes back to 2008 with the hope that it replaces the inevitable limitations of sinemet and rytary.

Sharon

rescuema profile image
rescuema in reply tosharoncrayn

They understand the implications, but no one has figured out yet whether it’s the chicken or the egg, including the latest finding on GABA production dysregulation prior to PD, before the dopaminergic neurons start to die off. Besides, it's already well known that the substantia nigra pars reticulata receives signal from the striatum, which is actually a term for caudate and putamen put together, and the pars compacta of SN communicates with the putamen via dopamine. Until a potential cure can be found through a gene therapy (probable), symptomatic relief through l-dopa remains valuable despite the side effects.

sharoncrayn profile image
sharoncrayn in reply torescuema

"They understand the implications.."

Once again, we agree to disagree on just about everything you have written.

Sharon

rescuema profile image
rescuema in reply tosharoncrayn

tou·ché

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