ambroxol trials any participants seen benefits?

[Coling]

i have been invited on a phase 2 trial of the above. I wonder if any conclusions can yet be drawn from this trial?

• Ambroxol,

• Doxycycline, or

• Ambroxol and Doxycycline combined.

[BlockRuys]

I am part of phase 3 Ambroxol study in the Netherlands. No benefits, pretty sure its placebo for me. The data is promising though especially for GBA1 carriers.

[JakeMax in reply to BlockRuys]

Hi Block, what does the data say for GBA1 carriers?

Many thanks

[BlockRuys in reply to JakeMax]

Here are some great references:

- Ambroxol - jamanetwork.com/journals/ja... && cureparkinsons.org.uk/2023/...

* The study results suggest that ambroxol therapy was safe and well tolerated; CSF penetration and target engagement of ambroxol were achieved, and CSF α-synuclein levels were increased. Placebo-controlled clinical trials are needed to examine whether ambroxol therapy is associated with changes in the natural progression of PD.

- Ambroxol reverses tau and α-synuclein accumulation in a cholinergic N370S GBA1 mutation model — ncbi.nlm.nih.gov/pmc/articl...

* Ambroxol increases glucocerebrosidase (GCase) activity and restores GCase translocation in primary patient-derived macrophages in Gaucher disease and Parkinsonism - pubmed.ncbi.nlm.nih.gov/336...

- Molecular mechanisms of the ambroxol action in Gaucher disease and GBA1 mutation-associated Parkinson disease - sciencedirect.com/science/a...

* One such a molecule that acts as a pharmacological chaperone for GCase was found to be ambroxol (2-amino-3,5-dibromo-N-[trans-4-hydroxycyclohexyl]benzylamine; Figure 1), found naturally in the Asian shrub Adhatoda vasica.

* However, some data have begun to question its activity as a chaperone against certain GCase variants. Then, a number of articles appeared pointing to other mechanisms of action of ambroxol, which may also contribute to the improvement of patients' condition.

[JakeMax in reply to BlockRuys]

Thanks Block!!!

[Coling in reply to BlockRuys]

Thankyou

[Jessica-1 in reply to BlockRuys]

have phase 3 results been published? How many people participated phase 3 trials? Many thanks.

[Coling in reply to BlockRuys]

Thanks BlockRuys when do you expect the results to be released?

[BlockRuys in reply to Coling]

late 2025

[Esperanto in reply to BlockRuys]

Hi Blockruys. Can you give us an update of the results of this trial of the UMCG in due course? 🙏

[BlockRuys in reply to Esperanto]

Certainly!

[Stillstandingstill]

Would individuals notice the benefit? It's my understanding that Ambroxol might slow progression, so without a control group an individual taking it wouldn't be able to gauge if it was helping or not. We will know in time as trials start to produce results.

[Jessica-1 in reply to Stillstandingstill]

The results that you mentioned are from phase 3 or phase 2 trail? Thanks.

[Stillstandingstill in reply to Jessica-1]

A phase 3 trial funded by the Cure Parkinson's Trust is just about to start in the UK. Sounds like there are other trials elsewhere too.

[Coling]

yes I am thinking has anyone had beneficial results from phase 2 trials ?

[BlockRuys]

YES!

"Mean (SD) scores on part 3 of the Movement Disorders Society Unified Parkinson Disease Rating Scale decreased (ie, improved) by 6.8 (7.1) points (95% CI, –10.4 to –3.1; P = .001). These changes were observed in patients with and without GBA1 mutations."

jamanetwork.com/journals/ja...

7 points is a lot better in MDS-UPD III.

[Coling]

many thanks