Medivation's most advanced compound is Dimebon, which enhances mitochondria function and is partnered with Pfizer (NYSE: PFE). It's believed that mitochondrial dysfunction leads to neuron death in neurodegenerative diseases like Alzheimer's and Huntington disease.

The first pivotal trial for Dimebon in Alzheimer's disease seems to have gone well, with Dimebon performing better than Aricept from Pfizer and Eisai, Razadyne from Johnson & Johnson (NYSE: JNJ), and Exelon from Novartis (NYSE: NVS) in at least one measurement. The caveat is that this wasn't a head-to-head trial, and comparing measurements across trials can be chancy because the trials may have enrolled patients with different characteristics.

Dimebon's next test will come from its phase 3 trial called Connection. The data is expected in the first half of the year, and Pfizer and Medivation could be filing for approval by year's end.
The companies are also testing Dimebon in a phase 3 trial in Huntington disease. PRESUMABLY, THEY WOULD MOVE INTO OTHER NEURODEGENERATIVE DISEASES LIKE PARKINSON'S AND ALS (amyotrophic lateral sclerosis) if Dimebon works in its current trials.

http://www.fool.com/investing/high-g...greatness.aspx

At what point would a drug like this new one and the other cholinesterase inhibitors [aricept, exelon, etc.] be prescribed? What determines the need for these drugs in a pd patient? i was given it just because of an off the cuff remark about azilect keeping me sharp and focused.

Isn't that a bit of an overkill to prescribe this for a little comment made? an observation? I took no mini mental test for this drug.

So does anyone know what determines that a pwp is demented enough to need these drugs? I think there is a reason they call the pwp community high achievers and smart as a chronically ill group.

It's as Lindy said, we have brain dysfunction, cognitive fog, loss of inhibitory mechanisms and impulse control, executive function, and more. But we do not have dementia in the way a typical person would envision it. Thus we are still here , getting smarter everyday by the way, just can't write, memory needs some help, can't make decisions, etc. But i am in my right mind as they say. We stay sharp because we are not low in acetylcholine.

However we do not want to overdose on acetycholine.

The last statement is more important than anyone realizes -pesticides bind to the cholinergic enzyme , thus allowing more acetylcholine in pwp. So we have the cognitive transmitter on overdrive, working against the dopamine, but still we stay smart. At first we are normal; then pesticides attack our cholinergic enzyme causing too much acetylcholine.

We spend the reset of our lives looking for a balance.

So what determines when a pwp might be lacking acetylcholine? Shouldn't they have severe deficits in memory - like forgetting where they are going or not recognizing relatives?

I think they should work on research /therapy to balance the transmitters and determine if high acetylcholine can diagnose pd in combination with other things. Logically we need something to keep acetylcholine low without the cognitive fog.

This drug may be different. But it seems like all they are working on is dementia with pd and alzheimers, as if they are the same.

Paula - I really think the answer to your question is "because they have no idea so are trying everything."

The real quest is to determine the exact nature and genesis of each of these different diseases with their multiple manifestations. Until then, any treatment or experiment that tries to impede, stop or cure progression is merely a shot in the dark.

Until there is some clarity about sub-types, and they are consistently defined I do not see how there can even be a point at which any trial or any guidelines could be used to say, this is the point at which we prescribe anti-dementia medication. There is a lot to say that medications themselves worsen dementia in the very old, in PD the borders are much more blurred, because for many people their actual diagnosis has not defined where they are on the PD spectrum, or even worse they have been arbitrarily dumped into a parkinsonism bin where their condition has not been properly evaluated. People who post and read boards like this are the educated tip of the ice-berg, often people who can and will question the medical advice and decisions made for them. Miles behind this are thousands who accept what they are told - so parkinsons or parkinsonism is a generalisation. To me this is where the real shot in the dark is - that not only do they not know the nature and genesis of the different diseases that they are attempting to treat, they have not even found a way yet to agree on the different flavours. With the PD spectrum this will never become clear until all the other stakeholders agree to engage with the patient.

(I wondered if this antihistamine had any mechanisms of action related to dextromethorphan (which is a morphine analog) whose primary actions for which PD patients use it are its anti NMDA actions(?)...Dimebon is also an NMDA antagonist, and in addition, affects Ca++ and mt permability pores.)

http://hdlighthouse.org/research/tri...nicaltrial.php
" Based on earlier work in Russia, it appears that this drug may regulate calcium homeostasis, prevent pathological opening of the mitochondrial permeability transition pores, and reduce the excitotoxicity of NMDA receptors.

References:

S. Bachurin, E. Bukatina, N. Lermontova, S. Tkachenko, A. Afanasiev, V. Grigoriev, I. Grigorieva, Yu. Ivanov, S. Sablin, and N. Zefirov. "Antihistamine Agent Dimebon As a Novel Neuroprotector and a Cognition Enhancer." Annals of the N.Y. Academy of Sciences 939(June 2001): 425-435.

S. Bachurin, E. P. Shevtsova, E. G. Kireeva, G. F. Oxenkrug, and S. O. Sablin. "Mitochondria as a Target for Neurotoxins and Neuroprotective Agents." Annals of the New York Academy of Sciences 993(May 2003):334-344. "

Abstract from Article related to Dimebon use in Huntington's @same web site:

"Dimebon(TM) has been shown to prevent the death of brain cells (neurons) in preclinical models of Alzheimer's disease and Huntington's disease, making it a novel potential treatment for many neurodegenerative diseases. Dimebon recently met all five efficacy endpoints in a six-month randomized, double-blinded, placebo-controlled trial of 183 patients with mild to moderate Alzheimer's disease. Patients in the trial were tested for a full spectrum of problems typically caused by Alzheimer's disease, including memory loss, behavioral disturbances, and inability to perform everyday activities such as bathing and dressing. After six months of treatment, patients on Dimebon got significantly better on all of these tests. Dimebon patients also scored significantly better on all of these tests than did placebo patients. Dimebon, which has a 20-year record of human use, also was very well tolerated in this study. Medivation and its advisors designed this study to match closely the design of pivotal registration studies previously accepted by the FDA to approve currently marketed Alzheimer's disease drugs, including duration of treatment, clinical endpoints and patient inclusion/exclusion criteria."

i was incorrect in the post above. this is one drug for alzheimers that is an antihistamine, not a cholinesterase inhibitor. Unfortunately, it did not meet its endpoints with advanced alzheimers.

paula
3/4/10