Thank you for posting this and what i am about to say is in no way a comment on that (or maybe you posted it for the reasons below - not sure what your intro line refers to) - my beef is with the status quo in industry and research in general. Also, this is pretty much off the cuff so might be a little less clear and organized than it could be.

I love the way motor complications are presented as if they just popped up a few months or even years ago - as opposed to the reality, which is that they have been glaringly evident since before levodopa went on the market in 1970, and this "effort" to fix them has been underway for just as long, i.e., some 36 years. and if you have ever just poked around on Pubmed, you will know that articles like this pop up regularly - and most of what they present is nothing new - but it is presented, like motor complications, as if it is breaking news.

Also, neuroprotective would be great, but do you see how it is presented only as a means to *delay* the need for pharmaceuticals? Why not *preclude* the need for pharmaceuticals? and why is it that we feel the *need* to delay the use? because the current set up doesn't work, that's why, and they know it, but it is the most lucrative for industry, having this base product that is in such need of bandaids that there is infinite capacity for growth in the selling of old and inventing of new bandaids.

I don't know if folks are aware of how entrenched the current set up is, in which several big pharmaceutical companies that make/market levodopa products also make the adjuncts that are supposed to fix the problems levodopa causes. Take Novartis, for example. Novartis markets Stalevo, levodopa/carbidopa/entacapone, which is manufactured by Orion, which has made entacapone, a COMT-inhibitor, since 1999.

Novartis owns 33% of Roche, which introduced the first two levodopa products ever back in the early 70's, one of which it definitely still makes - Roche Pharma funded and undertook a study in 1999 that found that their levodopa productt was even better with a COMT-inhibitor.

Novartis also makes bromocriptine.

Novartis' generic arm, Sandoz, makes, at the least, carbidopa/levodopa, amantadine (good for dyskinesias), amytriptyline (which i believe has an anti-cholinergic effect), and bromocriptine.

If you look at the product labeling for Stalevo, you will see that there is a 75% higher incidence of dyskinesias with levodopa/carbidopa/entacapone (they didn't actually test the single pill (containing all three drugs) form) - amantadine often helps alleviate dyskinesias.

Novartis appears to have sponsored the most recent Levodopa Consensus Conference (it issued the press release, at least), which took place either in Paris or a small, exclusive ski village in Switzerland (there have been two of these conferences - i can't remember which was where) and, surprise surprise, 30 of the top experts in the field agreed (unlike at the first levodopa consensus conference) that no one has proved the levodopa is toxic in vivo (its toxicity to dopaminergice neurons in vitro is not even debated), as if dyskinesias weren't proof enough, and that it remains "the gold standard."

Novartis has also paid for numerous Continuing Medical Education courses with titles like "The Future of Levodopa Therapy for Parkinson's Disease," that concludes with a plug for Stalevo ("The concurrent use of levodopa/carbidopa plus entacapone is now facilitated by the availability of a levodopa/carbidopa/entacapone combination product") including recommended dosages.

The above article does not require disclosures, but if you search around a little, you will find info like this about Robert A. Hauser, MD, one of the authors of the above course:

"Robert A. Hauser, MD, MBA, has disclosed that he has served as an investigator and on the advisory boards and speakers bureaus for Roche Laboratories, GlaxoSmithKline, Athena Neurosciences, Pfizer/Pharmacia, Medtronic, Novartis, Teva Pharmaceuticals, and Somerset Pharmaceuticals. He has also served as a consultant for Roche Laboratories, Somerset Pharmaceuticals, Merck (Germany), and Kyowa. He has also served on the Advisory Board of Watson Laboratories and as an investigator for Kyowa. Dr. Hauser has reported that he does not discuss any investigational or unlabeled uses of commercial products in this activity."

Roche, Novartis, Merck, Teva (or its generic arm, Ivax - could be both) and perhaps Somerset and Watson (don't have my notes with me) all make levodopa products, as does Novartis' generic arm. Kyowa is currently conducting clinical trials on a compound testing to see how well it manages motor complications. Medtronic, of course, is DBS, the *ultimate* "fix" for motor complications.

it is abundantly clear to me that industry has *zero* incentive to shake up the status quo by inventing a symptomtatic therapy that actually *works,* and the reference above to motor complications "having emerged" is, in my opinion, far from accidental - industry and researchers on its payroll intentionally perpetuate the impression that a) the problems have only recently made themselves known, and b) there are myriad "new" possibilities on the horizon - the problems are *not* new, most of the possibilities are not new, and levodopa is *still* broken, and that is the most lucrative set up for industry - always room for another adjunct, just don't threaten the foundation, levodopa, with a drug that actually works, cuz if you do, there goes your infinite capacity for growth in the adjunct realm.

at some point soon, i will be finishing an article on this subject.