The onslaught of recent interesting early pre-clinical and clinical research continued today with the release of these two studies"

An experimental treatment to help Parkinson's patients respond to medication better appears to be working

Voyager has created an enzyme, AADC, which allows the brain to continue to convert l-dopa into dopamine, even as the brain cells die off. It involves a one time surgery inserting the gene therapy into the putamen.

Voyager Therapeutics Parkinson's disease gene therapy shows progress - Business Insider

I'll post the other study on a separate thread.

From the MIT Technology Review article, which appears to me to be the basis for this Business Insider article:

“…the concept for the Parkinson’s gene therapy dates to 1986, when Bankiewicz first determined that too little AADC was the reason L-Dopa stops working.”

I don’t think I’ve seen it said elsewhere that this is the accepted reason why L-Dopa stops working. Might this be more of a theory than an established fact?

Anyway, they are making good progress, so let’s hope that the next trial confirms their past results!

https://www.technologyreview.com/s/6...-gene-therapy/

Well, what is fact is that AADC (aromatic L-amino acid decarboxylase) is the enzyme that metabolizes levodopa into dopamine. As we know, dopamine itself cannot pass through the BBB, but levodopa can. When we take oral levodopa, a small amount passes through the BBB into the brain and gets converted to dopamine by AADC. AADC will also convert levodopa into dopamine in the body. This is the reason why we also take Carbidopa, which is an inhibitor of AADC, and prevents the premature conversion of levodopa to dopamine in the body before it gets to the brain.

What we don't know is if the AADC gene created by Voyager, which gets implanted into the brain, will actually allow the dying dopamine producing cells to keep on converting levodopa into dopamine. That's what they will be researching.

Tupelo3 said:
"What we don't know is if the AADC enzyme created by Voyager, which gets implanted into the brain ..."

I may be splitting hairs here, but this is not quite correct, and I think it's worth getting it right. As I've said some time back on a different thread, I think that we should always try to make the effort to help each other out by pointing out errors whenever we spot them.

Voyager is not creating the AADC enzyme and implanting it into the brain. Voyager is modifying DNA so that the brain itself can create more AADC. As it says in the article you linked to: "The gene therapy goes in and helps the putamen produce new AADC enzymes, essentially creating a reservoir that can now be used to convert levodopa to dopamine."

That is why the Voyager CEO describes the treatment as "one and done". If Voyager was creating AADC they would need to do surgery regularly on each patient to "top up" the AADC.

This is interesting stuff, but it doesn't have much to do with the point I was trying to make. I realise that my point is a fairly subtle one, and I "umed and ahed" about whether or not to bother doing a post, but since I've done a post, I'll try to make my point a bit clearer.

All I am trying to say is that statements like the following quote from the article I linked to are, I believe, still subject to dispute within the research community: "The cause of Parkinson’s isn’t well understood, but the reason the drug wears off is. It’s because the brain also starts losing an enzyme known as ... AADC ..."

But the good news is, if the next trial (placebo controlled) confirms the previous results, then Voyager will have established two things:

(1) That L-Dopa wears off because (at least partly) of the loss of AADC.

(2) That Voyager's gene-therapy technology is effective in compensating for this loss.

Jeff

You're absolutely correct, Jeff, and I apologize for the error. That's what I get for responding quickly without reading what I write. What I had meant to say was the "AADC gene", not enzyme, and which I have corrected above. The drug, VY-AADC01, consists of a transfer vector, which is the virus AAV2, into which Voyager inserts their hAADC gene.

I think you're questions are good ones. I was really just focusing on what we know as fact, which is what the biological function is for the AADC enzyme. The rest all needs to be proven. It is certainly logical to think that a diminishing production of AADC would lead to l-dopa becoming increasingly ineffective, due to the inability to convert it into dopamine. However, there is also a whole school of thought that l-dopa stops working due to DNA methylation. I don't know how that fits into Voyager's research, but I'm certain there has to be some connection.

Gary