1. Aust N Z J Med. 2000 Feb;30(1):48-53.

The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the
clinical features of Parkinson's disease.

Reardon KA, Mendelsohn FA, Chai SY, Horne MK.

Neurosciences Department, Monash Medical Centre, Melbourne, Vic.

BACKGROUND: Animal studies have demonstrated an interaction within the striatum
between the angiotensin and dopaminergic systems. In rats, the angiotensin
converting enzyme (ACE) inhibitor, perindopril, crosses the blood brain barrier
and increases striatal dopamine synthesis and release. In humans, angiotensin
type 1 receptors have been found on dopaminergic neurons in the substantia nigra
and striatum. In Parkinson's disease, there is a marked reduction of these
receptors associated with the nigrostriatal dopaminergic neuron loss.
AIMS: We performed a double blind placebo controlled crossover pilot study in
seven patients to investigate the effect of the ACE inhibitor, perindopril on the
clinical features of moderately severe Parkinson's disease.
RESULTS: After a four week treatment period with perindopril, patients had a
faster onset in their motor response to L-dopa and a reduction in 'on phase' peak
dyskinesia, p=0.021 and p=0.014 respectively. Patients also reported more 'on'
periods during their waking day in their movement diary, p=0.007. Perindopril was
well tolerated without any significant postural hypotension or renal dysfunction.
CONCLUSIONS: These results suggest that ACE inhibitors such as perindopril may
have a place in the management of motor fluctuations and dyskinesia in
Parkinson's disease and justify further study.


PMID: 10800878 [PubMed - indexed for MEDLINE]

Now this was a small study, granted. But it was done with real PWP! Not rats, mice, or cell lines. And, as best I can tell, it was pretty much ignored. If one goes to Medline and searches for the combo of "ACE inhibitor" and "Parkinson's", one gets 22 hits.

Rick
I'm not trying to be a troublemaker, but what can/should we do about things like this? You understand the science far better than I do, so what does it mean if findings like this are ignored?

The trial that I participated in was halted inJuly, 2008. This was posted in the Michael J. Fox Foundation website about one week after the results were reported:
"In the first week of July 2008, Titan Pharmaceuticals, Inc., announced disappointing results from the Phase 2 trial of its symptomatic Parkinson’s therapy Spheramine. The announcement came in the wake of results showing that the experimental drug had failed to meet clinical endpoints outlined for the trial. Only one week earlier, the company had reported positive five-year data from its Phase 1 open-label trial of the same treatment."
source: http://www.michaeljfox.org/living_vi...ticle.cfm?ID=9

I was in Phase 1 - it was open label, meaning participants were told that they were getting the real stuff - no sham control. And as the Fox site says, 5 years later, they still were reporting positive results. My concern is nearly 3 years later there has still been NO OFFICIAL DATA REPORTS! (AT least not that the public can read - nothing has been published in a refereed journal, which is the protocol usually followed.)

How long must we wait? How can 5 years of positive resulls end with a negative 12-month follow-up to the sham control? And don't give me the "placebo" story - I feel there is s o much more at play here.

What next, Rick?
Peggy

This is a data base waiting to happen. Actually it would go well with the pipeline database but maybe we can contact swept and grey and see what they are starting as well as Tom.

list all the trials that have never published results, that disappeared. that isn't following up , etc. Let's see just how bad it is.the pipeline database, should be reviewed by the europeans to see if there are any missing treatments in development. then we could add more fields to reflect where they are now and disappearing trials. one of the fields should be not enough participants. However, I do not agree that patients should be intimitated or made to feel guilty for not being in one. Most patients have few resources or don't even know about them.

i still think the doctors should be approached about putting trials on a monitor in their offices. i'm on a participatory medicine listserve now that Doc John and John Lester are both members of. I am fortunate enough to read doctors and patients, many different related areas communicate. They are out there. today Doc John opened the archive to the public for reading but you have to join to post.

we need to pull all of these resources together. They are on our side.

so much more we can do. i can't even think in the morning but by this time sinemet is making me feel like i can do anything.

actually i have done quite alot. so we need to stop trashing sinemet ( talking about myself as well) or they are going to short it and try to get us to take what i kow for a fact is causing dyskinesia in who knows how many of us when taken with any other dopaminergic drug. if it's the combo [and it is for me i think] then we need an antidepressant , anticholinergic, and amantadine. i would go right downhill if i had to go back to dyskinesia.

ok i'm posting llike crazy and want to hear what some others think about doing a database. A few people were interested in doing an alternative medicine database and grey [from scotland] wrote and i think implied that he could include it in his but this must be checked. he is writing the software. as i said, this would go well within the pipeline database. I'll contact them in the UK and find out if they have started yet.

of course we don't have any money, so this database needs to be charity.
how else can we ever change anything anecdotally? we can't.

yes ten years have gone by. and i realize that we do need sinemet; we must say this loudly after dissing it for a long time. i wish i would have done this years ago but we are told that we need to avoid sinemet. not necessarily true - a shortage of regular sinemet would be potentially fatal to some of us.

You know, if there was going to be an opportunity for patients to take some control, make their point, and maybe even discover something important, it would be hard to come up with something more tailored to the problem than this.
1) ACE inhibitors are well known and available all over the world.
2) They are cheap and safe.
3) Many of us take hypertensive medications anyway, so it would be reasonable to ask for our GP's help.
4) It should be simple to design a study with some true value that is administered by the patients themselves. And it might be possible to get the original researchers to lend a hand in that part.
5) It could be ongoing and accumulate data. We could roll it out every couple of years as they are about to forget us again.

I started taking an ACE inhibitor two days ago. Unfortunately, I also began a Beta Blocker, so I'm not going to be a valuable White Rat. (I am trying to get a problem of too much aldosterone under control and both drugs were indicated. I was doing my homework for that when I came upon that paper.)

But I would be happy to help with it if we had a dozen or so PWP who wanted to try it. If we got to that point, we could move on and start working the Media.

The first step would be to design the study. KISS. Girija? Ol cs? RLSmi? Ron? Got it in you to ride at one more windmill? This one just might fall over.

BTW, here is some info on ACE inhibitors from Wikipedia-

"Angiotensin-converting enzyme inhibitors reduce the activity of the renin-angiotensin-aldosterone system.

ACE inhibitors are used primarily in the treatment of hypertension, though they are also sometimes used in patients with cardiac failure, renal disease or systemic sclerosis ACEIs can also be used to treat diabetic nephropathy and left ventricular hypertrophy.

For those who want to know about these drugs:

http://www.webmd.com/heart-disease/m...ace-inhibitors

I have been on Lisinopril for several years for B.P. purposes. Wonder if it would benefit taking a larger dose for P.D.?

Is there a doctor in the house???

(Remember that old song by Paul & Paula?) lol

I agree with you and was hoping somebody would catch onto the concept of patients demanding to see results. And what about scientists who cannot build their theories because of their lack of knowledge of all of those unpublished results?

Rick, yours is a concept that could be built equally as well into a database. We should put out those ideas of treatments or therapies that we KNOW work, and ask why they aren't being followed up. Back when I was volunteering a lot with a specific pharmaceutical company, they asked me to help "scout" for potential trials (they were a large enough company that they could buy out a trial that had potential. Money talks, you know.)

But, alas, we come to the problem of who will follow this up? Who will be in charge? Do we all do th e same thing?

Why am I always wanting to know the plan? (It's the teacher in me lol)

Peg