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Dimebon went down the tubes
JAB
Posted: Tuesday, January 17, 2012 5:05 PM
Joined: 11/30/2011
Posts: 740


"The last flickering hope that Medivation's Dimebon could help Alzheimer's disease patients has just been extinguished. The biotech announced this morning that a 12-month study of the drug failed to register significant improvements for patients, mirroring two shorter Phase III studies in which Dimebon failed to outperform a sugar pill. Pfizer ($PFE) took the opportunity to bow out of its partnership, writing off its $225 million upfront and $500 million milestone program for what proved to be another embarrassing pipeline failure..."

http://www.fiercebiotech.com/story/pfizer-writes-725m-dimebon-pact-after-final-phase-iii-failure/2012-01-17
skericheri
Posted: Monday, January 30, 2012 6:56 PM
Joined: 12/10/2011
Posts: 287


My Charlie, who died on 10/15/2011, participated in the Dimebon clinical trial from August 2008 until March 2010…Had been in receiving the ‘real thing’ for over a year and seemed to be in a holding pattern. After his leg of the trial was discontinued and I opted against obtaining the drug from sources outside of the US he went into a steady decline. I’m smart enough to be aware that his decline may have been normal or because the trial’s discontinuation robbed me of any hope.

I’m curious and wondering about the status of those who were also in the Dimebon trials and as well as those whose loved ones obtained the medication from other sources.

 

 Please check in and share your thoughts.



hmp100
Posted: Monday, January 30, 2012 10:18 PM
Joined: 1/24/2012
Posts: 16


Hello, skericheri.  I am so sorry to hear that you lost Charlie.  I watched your posts with admiration for so long as you strove to do everything you could for him.

 

My partner Steve is nearing the end of his 2-year supply of Dimebon obtained from Russia, and I have decided not to replenish the supply.

 

Since his diagnosis two and a half years ago, I have tried so many things as soon as I found out about them that it has been impossible to isolate cause and effect for any one thing:  MCT oil, Dimebon, cinnulin PF, grape seed extract, high bio-availability curcumin, saffron extract, chelation, and now magnesium L-threonate.

 

Of all these things, the only two that seemed to make any difference at all soon enough clearly to attribute changes to them have been the MCT oil and the magnesium.

 

The MCT oil has made the most difference.  His vision and motor skills improved quickly and significantly right after beginning the oil, and those improvements have been largely sustained.  In fact, I think the MCT oil has actually altered the course of his disease.  He began with posterior cortical atrophy, which normally leads to functional blindness and severe motor skill impairment well before severe global memory loss and intellectual impairment.  In his case, his vision and motor skills have largely held while full-blown Alzheimer's sets in.  (This result seems to track some of the early findings in recent studies of ketone body therapy which indicate it is more effective in reaching superficial rather than deep-lying brain tissue.)

 

In effect, the MCT oil doesn't seem to have staved off full-blown Alzheimer's, but he has possibly been spared the functional blindness and motor-skill loss that was to have been his lot along the way.

 

As his memory and aphasia is worsening quickly and apraxis is now setting in more or less "on schedule", I really cannot conclude that Dimebon has done anything for him.  At the time of diagnosis in August 2009 he was testing in the 17-19 range on the MMSE.  He is currently testing down near 10.

 

We try what we can.  And we hope.  That's all there is.


JAB
Posted: Tuesday, January 31, 2012 10:31 AM
Joined: 11/30/2011
Posts: 740


Hi, hmp100.  It's good to see you posting, but I am so sorry to hear Steve isn't doing well. 

 

 You may have noticed the thread about Axona ... the Accera folks are going after FDA approval of an IND based on the same basic treatment, with a Phase III clinical trial restricted to APOE4(-) patients.  I'll be looking forward to the results with great interest.

 

Like Cherie, my husband was in a dimebon trial and on "the real thing" for over a year.  (Actually, I've always been convinced he was on dimebon during the double-blind phase, too, given his reaction to the first pill.)  And while the results were not really obvious right away, it did seem that the rollercoaster track was raised a bit, and he could communicate more easily and was more oriented and interested in life, and he held steady and possibly improved a bit during that time.  And ... he also declined when Pfizer pulled the plug.  It could have been that, it could have been a stroke, it could have been another med his idiot now-ex-doctor put him on, it could have been parkinsonism developing, who knows.


judysguy
Posted: Wednesday, March 14, 2012 2:31 PM
Joined: 12/17/2011
Posts: 11


Hello hmp100,

My wife also has posterior cortical atrophy but as I mentioned in a post in the Axona thread MCT oil has not helped.

 

Although I've read a few papers on visual variant that the Alzheimer's Association care consultant sent me, I didn't realize that it tended to overrun the general Alzheimer's decline.  So far I've just seen some problems identifying things ("Is that a child under that bush?") or in walking.  Paths in our woods that used to be an easy stroll have become difficult for her and we are having to focus on going where there is pavement.

Do you have some sources of information on PCA that you could pass on to me?  It looks like I'd better start preparing myself more for the changes ahead.  (She was 18 on the MMSE last year.  We go in for an annual check at the U. of Washington AD research center next month and I expect her to be much lower by now.)


hmp100
Posted: Wednesday, March 14, 2012 5:19 PM
Joined: 1/24/2012
Posts: 16


I'm sorry, Judysguy, but I have found almost nothing on PCA.  Except for the neurologist who diagnosed it, most of the doctors he has seen have never even heard of it.

 

Steve walks by himself for two to four loops around our development each day (at 2.75 miles per loop) and often comes home to tell me about conversations he had with other walkers.  There have been two interesting developments regarding his walking ability since beginning MCT oil.

 

For some years prior to being diagnosed, Steve shuffled badly when he walked and often stumbled into things.  (I used to grind my teeth wondering how long the carpet could take the foot dragging.)  And during the spring and summer before his diagnosis when we often took walks together, his walking was getting slower and slower.

 

But in the two and a half years since beginning the MCT oil, his walk has normalized, and it did so quickly.  The shuffling is completely gone, he seldom stumbles into things, and his walk is brisk again.

 

On the other hand, his vision does seems to be deteriorating a bit.  He takes the dog out for a walk on this first loop each morning, and he says he can no longer tell whether she is relieving herself.  He says she just blends into things.  He has given up any attempts to read, and recently he mentioned for the first time that he had been having trouble seeing the TV screen.  (However, he mentioned that in the context of saying that he was now seeing the screen more clearly -- and that was a couple of weeks after beginning him on, of all things, aroma therapy.)

 

There are a couple of other development since I last posted about starting him on aroma therapy.  He had completely lost the ability to tie his shoes.  He can now sometimes tie at least one of them.

 

Also, he likes to wear sweatpants but had become unable some months ago to put them on by himself.  He could not see the inside label that told him which direction was the back, nor could he understand when I instructed him how to turn the pants so that the label was at the back.  Then a couple of weeks back, he began coming out from his shower with his sweatpants already on, asking me if he had it right.  He almost always does.  I asked him what changed, and he said he could see the label better.

 

And there is one other change that pulls both ways.  His difficultly in expressing thoughts without losing the words has worsened in recent months, but his impulse to be more conversational has strengthened.  In fact, he has recently begun to want to chat during a meal or while we're sitting on the lanai, much as he used to.

 

Part of me still says "flaky" every time I utter the words "aroma therapy".  But I'm damned if I don't see some improvements in at least some dimensions that I cannot attribute to any other cause.

 


judysguy
Posted: Wednesday, March 14, 2012 8:26 PM
Joined: 12/17/2011
Posts: 11


hmp100, thanks for the response. 

 

It sounds like I got more from the care consultant than you've been able to get from the docs.  I'll re-read what I have and could certainly pass on what I've got but it sounds like you're pretty aware, just from what Steve has been going through.  It gives me an idea of what maybe to expect, except we are all aware that our person doesn't necessarily experience what others do.

I just ran across some of my notes from a couple of years ago saying that destruction of the parietal lobs results in problems integrating visual, auditory and body sensation information which might explain why my wife is having problems with incontinence way earlier than I expected.

I wish the MCT oil had helped but I'm not sure I'm ready to chase anything else.  I probably need to use what little time I have beyond daily caregiving to be learning more about how things are going to change so I can maybe be prepared.

The best aromatherapy I can think of is when I start sauteeing onions and garlic in olive oil for our dinner.  Cheers up the caregiver, anyway.

 


hmp100
Posted: Wednesday, March 14, 2012 10:14 PM
Joined: 1/24/2012
Posts: 16


You probably know that posterior cortical atrophy (PCA) wasn't even identified as a disease until 1988.  While it's often referred to as a variant of Alzheimer's disease, there is not even agreement within the medical community as to whether it is a subcategory of AD or whether it is an independent disease.

 

 

There has been almost no research directed specifically at PCA, and doctors just go on the assumption that the same medicines that are approved to address AD symptoms will work the same way with PCA symptoms.  (That's the reason that the British author Terry Pratchett, who has PCA, donated $1 million a few years back to try to jump start interest in research on the disease.)

 

 

Most importantly, there is no understanding of why PCA -- if it is, in fact, a form of AD -- affects an atypical part of the brain first and why it strikes earlier than the prevalent form of AD.  It would seem to me that ferreting out the reasons for those differences might offer new clues both to PCA and AD.

  

 

I have read things about PCA such as, "if you're going to have AD, it's the form to have".  Sadly, I don't see it that way.

 

 

For starters, the typical time from diagnosis to death is 8-12 years . . . no better than with AD.

 

 

Also, PCA sufferers often retain enough cognitive ability late into the disease to feel the full impact of the ravages it is exacting on their vision and motor skills.  My partner was a school teacher and a voracious reader.  He suffered more from the loss of his reading ability than from a prognosis of certain death from this disease.  And now he is still aware enough to fear the loss of his remaining visual ability.  I used to try to explain to him the difference between the functional blindness of PCA and true blindness, but it was a fool's errand.

 

 

He knew -- and still knows -- that this pig just won't wear lipstick.


judysguy
Posted: Friday, March 16, 2012 10:45 AM
Joined: 12/17/2011
Posts: 11


hmp100 wrote:

You probably know that posterior cortical atrophy (PCA) wasn't even identified as a disease until 1988.  While it's often referred to as a variant of Alzheimer's disease, there is not even agreement within the medical community as to whether it is a subcategory of AD or whether it is an independent disease.

 

 

I wasn't aware of that.  The psychiatrist at the U of Washington ADRC that told me Judy had visual variant of AD and the information from the care consultant was directed at visual changes in people with AD, although it noted that visual changes might be the first changes rather than amnesia.

I also didn't know that Terry Pratchett, one of my favorite authors, had PCA as I've always seen him described as having early onset.  I guess that tells us how little is known of PCA.

I couldn't find the papers I'd originally printed out on PubMed but looking at the abstracts of reviews it looks like PCA is a grab bag of different dementias including AD, FTP, Lewy Body and prion disease: different underlying biology but similar results.

I would guess that Judy has amnesticAD  with the visual variant rather than PCA like Steve has, although it is hard to sort it out.  She first had problems organizing, followed by getting lost driving, then short term memory.  The visual problems explain why she stopped reading (an avid reader like Steve) and why text-based memory aids didn't work when she was mild stage.  However, there is a serious memory problem involved:  I certainly wouldn't trust her to do a loop of a development like Steve can without getting lost and forgetting what she was doing since she has a hard time finding her way to the bathroom in our house where we've lived 25 years.  She also is aware of the changes in her abilities as Steve is, and is quite frustrated by them.

Thank you for the information.  There is NO form of AD that is better to have than another, as far as I'm concerned.

 


hmp100
Posted: Friday, March 16, 2012 4:49 PM
Joined: 1/24/2012
Posts: 16


Actually, there are quite a few similarities you describe, Judysguy, between Steve's symptoms and your wife's.

 

Although Steve has been walking the loop around our community without incident, he, too, can forget where our bathrooms are.  A couple of days ago, he and I got up to use the bathroom at the same time.  I went to one bathroom and he walked off toward another.  When I finished, I found him standing in a hallway, angry and confused.  I asked what was the matter, and he said there was someone in every bathroom he went into.  (We have 5 bathrooms; we two were the only ones in the house.)

 

We are in a walled-in gated community with only one exit past a guardhouse manned 24/7.  The guards and the association staff are aware of Steve's condition and how to reach me.  He also carries ID with his condition, his address, and my name and phone numbers on it.  I have given the same cards to our nearby neighbors.  I worry constantly about his walking, but he tells me every few days how much he enjoys it as it is the only time he feels he has any degree of independence left.  (I do, however, usually get into the car and take a ride around the community just to be sure he is on track.  If he sees me, I stop and tell him I'm on the way to run an errand.)

 

Steve's symptoms first began with lack of organization, too.  In fact, he resigned from teaching in 2005 due to it, even though it was 2009 before he was properly diagnosed.   (PCA is frequently misdiagnosed as one psychiatric disorder or another in the early stages, because few doctors are aware of it, and it typically strikes in the early-50's when dementia is not the first place doctors go.  Steve was misdiagnosed -- and consequently mis-medicated -- for OCD and bipolar disorder.  In fact, the sudden total cognitive collapse he had in May 2009 occurred right after a psychiatrist put him on Abilify, an anti-depressant that is known to be a high risk for patients with dementia.)

 

 

The disorganization was followed by constantly misplacing things and beginning to have a rash of small accidents when driving (usually hitting stationary objects, but not always).  A couple of times I had him follow me in his car to drop off my car for service.  I turned into the dealership, and he just sailed on by.  (He has not been behind the wheel since the day he was diagnosed.)

 

 

Then his working memory failed, and he could no longer do things in a logical sequence.  He would start to cook dinner and unwrap a piece of raw meat and just stand in the middle of the kitchen with it, having forgotten to put out a plate or cutting board.  Then he began leaving burners on and water running.

 

 

And so it went . . . and so it goes.

 

 


judysguy
Posted: Saturday, March 17, 2012 11:07 PM
Joined: 12/17/2011
Posts: 11


I think it is wonderful that you've been able to put together a situation where

Steve can walk outside and feel independent while you know that he is OK.  Loss of independence is one of the factors behind Judy's wanting to "go home."  Home is where she can come and go as she pleases and things are predictable.  In other words, that past we will never regain.  I'm very sorry to hear that Steve was misdiagnosed and that may have led to faster development of his illness.

Our gated community (consisting of Judy, me and the dog) is 10 acres of Pacific Northwest forest with a pond I want Judy to stay out of and that has a busy county road with no shoulders on the other side of the gate. Not exactly the place for someone with dementia to be wandering.  That's why I have door alarms and top and bottom slide bolts so when she decides she wants to "go home" in the middle of the night wearing her nightshirt and slippers I'm alerted.  That's also why we are going to be selling our place and buying property with out son and his family so we have a better-contained environment.  The downside is being in a new setting that she probably can't learn but she's having problems in the home we built from scratch and have lived in for 24 years anyway.

Thank you for sharing some of Steve's situation as it has highlighted for me the need to keep Judy's visual problems in the forefront of my planning.  It seems like the visual changes are coming rapidly.  In the fall of 2009, right after we got her diagnosis, she was walking along trails cut into the cliffs of Zion National Park and scrambling through slot canyons off trail.  Now she can't tell the difference between the trail in our "North Woods" (linear, mostly smooth and covered with leaf mold) and the woods (knee-high ferns, brush, and deadfalls between the trees, very difficult to walk in).  She has to walk very slowly behind me, holding on to my hand.  Even on pavement she walks slowly and is being to shuffle some. I used to have to hustle to keep up with her going across a parking lot.

I guess not recognizing home and not recognizing me sometimes is pretty common in people with AD but I assume the visual variant is why it seems to be coming so soon after diagnosis.

 

As you said, so it continues to go.  And at an unpredictable speed.