Call for Study Participants

I received this call for study participants from an organization who came across this blog. Their site looks good and their research intentions appear to be on the "up and up." However, I am not recommending or referring anyone based on my first hand experience with them and take no responsibility posting this. As in any situation, careful study and asking questions is your guide to making good decisions.

Fondly, Michael

 Hi Michael,

I came across your blog and its dedication to Alzheimer’s disease.  (AD) 

My partner and I own a clinical research facility on the corner of Foster and Ashland.   We’ve been open over a year, though our staff has many years of experience.  

We’re currently conducting several Alzheimer’s trials and have several more in our pipeline.  Two current trials are for those already with mild to moderate AD and a third (opening soon!) is an AD prevention trial called A4.

A4 is sponsored the the National Institute of Health (NIH).  This trial is for those 65 and over who are healthy and not showing signs of AD.  PET scans and MRI’s are used to see if those screening have the signs of AD in their brains (plaque/Amyloid/tangles), though not yet showing signs of the disease.  An investigational medication is being used to see if AD can be stopped before it becomes symptomatic.   

All three trials that we’re doing are designed to stop, slow down or prevent AD from happening.  Instead of treating only symptoms, these are “disease altering investigational medications.”  There’s NOTHING on the market now that attempts to do that.  If I had AD, I’d enter a clinical trial because there is nothing to stop it from progressing and by entering a clinical trial, I might be able to benefit from it, but for sure, others will too.

We are having a very hard time recruiting volunteers for our trials.  We don’t know why, but we need a number of people who have AD already for us to continue this valuable research in the hopes of finding a cure.   

Is there anyway you can help us get the word out?  It seems like such a waste that this option is available to people with AD, though few are taking advantage of it.

Thanks for you time reading this.   D

www.greatlakesclinicaltrials.com 

Dean Hervochon, Executive Vice President

Great Lakes Clinical Trials

5149 North Ashland Avenue
Chicago, IL 60640 USA

Mobile:  (773) 454-1312

Phone:  (773) 275-3500

Fax: (773) 275-3501
Email: dhervochon@greatlakesclinicaltrials.com

The State of Alzheimer's Research

Samuel Cohen says that Alzheimer's is not normal aging and that we can cure it! 

See the TED prevention by clicking here.

Possible Good News

From the column 'The VICE Guide to Right Now'

This article originally appeared on VICE UK.

A new drug that could reduce the effect of Alzheimer's disease by 30 percent has just been revealed at today's Alzheimer's Association International Conference in Washington, DC.

One thousand patients were given an infusion of an antibody called solanezumab once a month, over a period of one-and-a-half years, and the study has shown that the antibody significantly reduces the decline in brain function of patients in the early stages of the disease. As Dr. Eric Siemers from the Lilly Research Laboratories, in Indiana, told the BBC, "It's another piece of evidence that solanezumab does have an effect on the underlying disease pathology."

It's not a cure, but this does come as something of a breakthrough, since older Alzheimer drugs only tackle the symptoms. Now, the new drug should reduce the rate at which the disease takes over a person, meaning more people who suffer from the disease could potentially live longer.

An earlier 18-month trial of solanezumab ended in failure in 2012, but this one serves as a landmark moment—as a representative the Alzheimer's Research branch in the UK put it, if this gets replicated, then it's "a real breakthrough in Alzheimer's research."

In the UK, some 850,000 people suffer from the disease, with this number expected to rise to 1 million by 2025. Of America's top ten causes of death, Alzheimer's is the only disease that cannot be prevented, cured, or slowed. Every 67 seconds, someone in the US develops the disease. Solanezumab looks like it could at least prolong a sufferer's life span. A new trial on the antibody, to begin next year, should tell us for sure.

Researchers and Their Studies

Aaron, a researcher and doctoral student who has "adopted Gregory and me" as part of his dissertation on care giving couples writes: "I've been keeping up with the blog. Sounds like things continue to be interesting, challenging, frustrating, sad, loving, good, bad, all that this journey is -- and you two keep moving through it with typical M&G grace. I look forward to being able to catch up in person sometime soon."

I replied: "Your descriptors of G and my journey according to your keeping up with my BLOG almost make what we are going through seem romantic. I do not mean to be sarcastic but I have felt so sad, and heavy lately with no where to turn for escape. I have been struggling with both arm's rotator cuffs being "out." No precipitating cause so I kiddingly call it the "Atlas Syndrow."

"I have quickly jumped on getting them back into working order by acupuncture, massage, physical therapy, exercises, alternating cold and hot, homeopathic creams, and pills under my tongue. I am feeling better but everyone tells me it will be a long, slow process. I am not giving up. I am treating it like a "bad cold" which I am taking care of and which eventually will go away.

"But it has been hard "Keeping Calm and Carrying On" for both of us when I feel so functionally limited. G continue to not know the front from the back of his underwear, the microwave from the refrigerator, yes from no. We have been enjoying may movies at home, some theater out, my cooking delicious meals, and now we will go have a slice of sour cherry pie just out of the oven. Which you were here to share it with us.

"Hope you are being "a good boy" and doing what you need to do to get your studies completed with a Dr. added on the front. Take care. When we get close to the 25 or 26 we can make more detailed plans,

We both really enjoy our time with Aaron. He is a good hearted person and a good listener besides a good cook. I have always said that being part of a research study (and we have been through three or four by now.) It is a good experience because the researcher pays attention to Gregory and causes me to think through the nature of and lessons learned from our journey. Also, the researcher actually wants to hear what I have to say without my worrying about boring him or her. Honestly, what we say might help others, but really we benefit the most and feel selfish about it!

New Research

New York Times July 11, 2012

In Preventing Alzheimer’s, Mutation

May Aid Drug Quest

By GINA KOLATA

A study of a rare gene mutation that protects people against Alzheimer’s disease provides the strongest evidence yet that excessive levels of a normal brain substance, beta amyloid, are a driving force in the disease — bolstering hopes that anti-amyloid drugs already under development might alter the disease’s course or even prevent it.

So far, the drugs have not succeeded. But scientists not connected with the new study said it suggested that the drug companies’ big bets on anti-amyloid treatments could yet pay off.

The implication for drug development “is hugely important,” said Dr. David Altshuler, a genomics expert at Harvard Medical School and the Broad Institute of Harvard and M.I.T.

And Dr. Samuel Gandy, an Alzheimer’s researcher who directs the Mount Sinai Center for Cognitive Health, called the finding the most significant in the field in two decades, since researchers first reported a mutation that leads to the disease.

The protective mutation, whose discovery was reported online Wednesday in the journal Nature, is highly uncommon — it is not the reason most people do not develop Alzheimer’s. But what intrigues researchers is how it protects the brain.

Mutations that cause Alzheimer’s lead to excessive amounts of beta amyloid in the brain; by contrast, the protective mutation slows beta amyloid production, so people make much less.

“This paper provides strong evidence that it would work in the general population if you did it right,” Dr. Altshuler said.

Scientists at the drug companies agreed. “We are thrilled,” said Ryan Watts, one of the authors of the new paper and head of the neurodegeneration labs at Genentech, which

is developing two drugs to reduce brain amyloid levels.

Dr. Richard Mohs, leader of neuroscience early clinical development at Eli Lilly, said the company was “very encouraged by these study results.” They show, he said, that despite an initial failure, the strategy of focusing on drugs to reduce beta amyloid levels is “a logical path for the development of effective therapies that may slow disease progression.”

Many questions remain, of course. Most people do not have the protective gene mutation, but as common as Alzheimer’s is, most people do not get it. It is not clear why. And most who develop Alzheimer’s do not have one of the rare gene mutations that cause it. The reasons for their disease are unclear.

The discovery of the protective gene mutation, a product of the revolution that has taken place in genetics, arose when researchers scanned the entire DNA of 1,795 Icelanders.

About 1 in 100 had a mutation in the gene for a large protein that is sliced to form beta amyloid. Then the investigators studied people who had been given an Alzheimer’s diagnosis, and a group of people 85 and older. Those with the mutation appeared to be protected from Alzheimer’s disease.

The investigators, led by Dr. Kari Stefansson, chief executive at DeCode Genetics, an Icelandic company, looked at genomes of North Americans and found the gene mutation in only about 1 in 10,000 people. That indicates, Dr. Stefansson said, that the mutation arose relatively recently in Scandinavia.

The protective gene even appears to override a very strong risk factor for Alzheimer’s disease in old age — two copies of a gene known as ApoE4. Ninety percent of people with two ApoE4 genes get Alzheimer’s by age 80. But Dr. Stefansson says there are 25 people in his study with two copies of ApoE4. None have Alzheimer’s disease.

The research “is obviously right,” said John Hardy, an Alzheimer’s researcher at University College London and a discoverer of the first gene mutation found to cause the disease. “The statistics and the finding are pretty secure.”

The discovery is part of a continuing story that implicates beta amyloid as a central and crucial player in this destructive brain disease. The idea began two decades ago with the discovery of very rare gene mutations that always cause Alzheimer’s in those who inherit them, usually by middle age. The mutations were different in different families,

but all had the same effect: They increased the amount of beta amyloid in the brain. That meant that a buildup of amyloid was sufficient to cause the disease.

Elderly people with Alzheimer’s — who typically do not have these gene mutations — also had excess amyloid in the brain. So researchers reasoned that might mean that excess amyloid was causing the disease in them, too.

Additional evidence of the role of beta amyloid was reported on Wednesday in The New England Journal of Medicine. Using spinal taps and brain scans to track the protein, investigators found that people with one of the Alzheimer’s-causing mutations start making too much beta amyloid as long as 20 years before they have symptoms of the disease.

Researchers and drug companies focused on the amyloid hypothesis to the extent that almost every experimental drug being tested to slow or halt Alzheimer’s disease is designed to reduce the amount of amyloid in the brain. Most of those drugs are still being tested in clinical trials, but a Lilly drug that failed spectacularly in 2010, semagacestat, actually made people with Alzheimer’s worse and gave rise to soul- searching in the field.

It emphasized a crucial question that hung over the endeavor. Was amyloid really causing Alzheimer’s in elderly people? Might the protein instead be a bystander, accumulating, for example, as part of the brain’s response to damage?

The discovery of the protective gene mutation provides strong clues. People with the mutation make substantially less beta amyloid, but other than that they are no different from anyone else. And they do not get Alzheimer’s.

People could be tested to see if they have the protective mutation, Dr. Stefansson said, but he added, “The benefits of doing so are not obvious to me.” He explained that since the gene is so rare, chances that a person being tested would have it — especially if that person is not Scandinavian — are extremely low. Almost everyone would end up with the same uncertainty they have now. There is as yet no way to prevent Alzheimer’s and, outside of families with one of the rare disease-causing gene mutations, no way to know who is going to get it.

Still, Dr. Hardy noted, as provocative as the discovery of the protective gene mutation is, the strategy of reducing amyloid levels — the ultimate test of the amyloid hypothesis — still must be evaluated in typical Alzheimer’s disease. For example, perhaps people need to have lower levels of beta amyloid from birth to really be protected.

Researchers and companies explain away the failure of the first few experimental drugs to reduce beta amyloid levels or to block the protein by saying they were not powerful enough and were studied in people who already had the disease and clear symptoms of mental decline. By then it might be too late to make any difference. When brain cells have died, nothing can bring them back.

The strategy now is to use new brain scans and other methods to find and treat people before they have symptoms of mental decline.

“The idea is that treatment has to start early to make a difference,” Dr. Watts said.

Of course, people with the newly discovered mutation have lower levels of beta amyloid for their entire lives.

“You couldn’t start earlier than that,” Dr. Watts said. 

New Hope

Woa! It has been along time since I posted. Partly because we are getting ready to visit family & friends in TX and then on to MX for a month. I am sure I'll do a lot more posting then. Meanwhile, this article in the Wall Street Journal caught my attention. Very interesting. Will do a follow up post on the image of the mice.

• HEALTH & WELLNESS
• FEBRUARY 10, 2012

New Attack on Alzheimer's

Cancer Drug Reverses Disease's Symptoms in Mice; Human Tests to Start Soon

By GAUTAM NAIK

A cancer drug quickly and dramatically improved brain function and social ability and restored the sense of smell in mice bred with a form of Alzheimer's disease, suggesting a new way to tackle the illness in people.

Alzheimer's is associated with the accumulation of protein fragments called amyloid-beta in the brain. The new research found that an existing skin-cancer drug called bexarotene cleared the protein in the brains of stricken mice within days. The study was published Thursday in the journal Science.

A skin-cancer drug has shown some success in treating Alzheimer's disease in mice, according to a study in Science. Stefanie Ilgenfritz has details on The News Hub.

Because bexarotene is known to be safe for treating skin cancer, "it might be worth trying in Alzheimer's patients as well," said Rada Koldamova, a neuroscientist who works on Alzheimer's at the University of Pittsburgh and wasn't involved in the study. However, she added, the drug's effectiveness against the brain malady would first have to be established in human trials. Test results in mice often don't pan out in humans.

Everyone's brain produces amyloid-beta protein, but while a healthy brain can efficiently remove the protein fragments, the brain of a person with Alzheimer's can't. The resulting buildup is believed to result in impaired learning and memory functions.

The disease is a growing problem, especially in aging societies, but no effective treatment has been found. The drugs used today work just for a short time and only relieve symptoms, instead of halting the disease. Over the years, drugs in about a half-dozen late-stage human trials have failed to make the cut.

In 2010, Eli Lilly & Co. abandoned a treatment that blocked an enzyme linked to amyloid formation after the drug appeared to worsen some patients' condition. Another technique, currently being tested in patients, is to reduce protein formation by triggering an immune response.

The new research, funded by a number of foundations, takes a completely different approach, said Gary Landreth, a neuroscientist at Case Western Reserve University in Cleveland and a co-author of the study. His team's method, he said, is to "help Mother Nature do what she normally does" in clearing amyloid fragments from the brain.

Scientists know that a protein called ApoE acts as a sort of garbage-disposal unit, helping to degrade amyloid-beta proteins. Dr. Landreth figured that if he could get the brain to make more ApoE, the protein clearance would be enhanced.

He set his sights on bexarotene, an orally administered drug known to activate a protein that helps switch on the ApoE gene. In 2009, Dr. Landreth asked a newly minted postgraduate student in his lab to give the drug to some "Alzheimer mice." Three days later, the amyloid plaques in their brains had largely disappeared.

"It was unprecedented," Dr. Landreth recalled. "I initially thought she had screwed up."

In the Science report, Dr. Landreth and his colleagues describe similar tests done with over 100 mice. When the drug was fed to mice with Alzheimer-like symptoms, it quickly improved their cognitive, social and olfactory functions. Losing the sense of smell, a disorienting and often debilitating experience, can be one of the first signs of Alzheimer's in humans.

Healthy mice typically will gather tissue paper strewn around their cage and use it to make a nest. Alzheimer mice stop doing that. When the drug was given to diseased mice they made nests, a sign of cognitive improvement. The benefits lasted up to three months, at which stage the scientists stopped their observations because that was sufficient time to show the drug's effects weren't transitory.

It is widely believed that the memory problems seen in the affected mice and human Alzheimer patients are caused by small soluble forms of amyloid beta. The researchers found that within a mere six hours of getting the drug, soluble amyloid levels had dropped by 25%. This effect lasted for three days.

In the U.S., bexarotene is sold under the name Targretin, which is owned and marketed by Japan's Eisai Co. Patents on the drug—and hence its profitability—will start to expire this year, one reason drug companies may be reluctant to jump on bexarotene as a possible Alzheimer's treatment.

Dr. Landreth and a study co-author, Paige Cramer, are founding scientists of ReXceptor Inc., which has licensing options from Case Western to use bexarotene to treat Alzheimer's disease.

Bexarotene is a long way from being an approved Alzheimer's drug, or even being deemed ready for off-label use—when a doctor legally prescribes a drug for an unapproved use. As a first step, Dr. Landreth plans to start a safety trial in a dozen patients in the next few weeks.

He needs to figure out the right dose and duration of the treatment for prospective Alzheimer's patients, and judge the effects over several months. If all goes well, he hopes to engineer a version of the medicine that is more potent and works at a lower dose, to minimize any side effects.

Carl Wagner, an organic chemist at Arizona State University who is collaborating with Dr. Landreth on the project, said he had synthesized half a dozen such versions and was testing them.

Write to Gautam Naik at gautam.naik@wsj.com

Copyright 2012 Dow Jones & Company, Inc. All Rights Reserved

This copy is for your personal, non-commercial use only. Distribution and use of this material are governed by our Subscriber Agreement and by copyright law. For non-personal use or to order multiple copies, please contact Dow Jones Reprints at 1-800-843-0008 or visit

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My Little Boy

Just got home from a fun day with Gregory at Michael's Museum. Our massage therapist, her husband, and our new friend Aaron (who is also using us for part of his phd research on Care Giver Relationships) visited CCM and MM today and then we all went out to lunch.

When we arrived home I settled in to catch up on e-mails, paying bills, etc. Gregory seemed a little restless and was rummaging around so I asked, "Is everything Ok?"

He said, "Well, no."

"What's the problem?" I asked.

"I don't have anything to play with," was the response.

Turns out he recently finished his jig saw puzzles, cleaned off his desk to make room for the Christmas decorations, and is almost finished with the book he is currently reading. In his mind, and as he becomes more and more "my little boy," he felt that he didn't have anything to occupy his time, in other words, "I don't have anything to play with." Do you feel the beauty in this? I do. It is one of the gifts of Alzheimer's!

I Have Lost Myself

SPOILER: HEAVY READING AHEAD...

In 1996, Dr. Konrad Maurer and his colleagues, Drs. Volk and Gerbaldo, rediscovered the medical record of Auguste Deter. In it Dr. Alzheimer had recorded his examination of his patient,

"What is your name?“

"Auguste.“

"Family name?“

"Auguste.“

"What is your husband's name?“ - she hesitates, finally answers:

"I believe ... Auguste.“

"Your husband?“

"Oh, so!“

"How old are you?“

"Fifty-one.“

"Where do you live?“

"Oh, you have been to our place“

"Are you married?“

"Oh, I am so confused.“

"Where are you right now?“

"Here and everywhere, here and now, you must not think badly of me.“

"Where are you at the moment?“

"This is where I will live.“

"Where is your bed?“

"Where should it be?“

Around midday, Frau Auguste D. ate pork and cauliflower.

"What are you eating?“

"Spinach.“ (She was chewing meat.)

"What are you eating now?“

"First I eat potatoes and then horseradish.“

"Write a '5'."

She writes: "A woman"

"Write an '8'."

She writes: "Auguste" (While she is writing she again says, "It's like I have lost myself.")

Alzheimer concluded that she had no sense of time or place. She could barely remember details of her life and frequently gave answers that had nothing to do with the question and were incoherent. Her moods changed rapidly between anxiety, mistrust, withdrawal and 'whininess'. They could not let her wander around the wards because she would accost other patients who would then assault her. It was not the first time that Alzheimer had seen a complete degeneration of the psyche in patients, but previously the patients had been in their seventies. Deter piqued his curiosity because she was much younger. In the weeks following, he continued to question her and record her responses. She frequently responded, "Oh, God!", and, "I seem to have lost myself". She seemed to be consciously aware of her helplessness. Alzheimer called it the "Disease of Forgetfulness".

CUE THE TEARS ...

Setting Expectations

I am part of an online Alzheimer's Support Group called "Circle of Care" which is sponsored by the Novartis Drug Company. This is a chain of conversation which I recently had with Deborah, one of the facilitators.


INTRODUCTION: Hundreds of years ago, the medicine we have today would have seemed like magic. Today we know that medicine is all about science and each medicine works in very specific ways. How we learn about the ways a medicine might work is varied though – some of us gather information online, some from our MDs and some from friends and family – or maybe a mix of it all. In this discussion, we want you to think back to when your loved one first started their current medication for Alzheimer’s disease or dementia and tell us a bit about your expectations of the medication at that time.


MY REPLY: Right from the beginning the doctors said that Aricept and Namenda would only slow down the disease NOT cure it. We were surprised when Gregory began first Aricept his functioning improved greatly. If he had been functioning at 60%, he shot back up to 80%. Doctors and we were pleased. Then within a few months the functioning was on a downward roller coaster ride so we began Namenda. The same amazing improvement happened and the decline has been very slow since. We still do not expect things to ever be normal again but I do believe the medications have helped. Just recently Aricept has been approved at a little over double the dose and we have begun taking them. Here's hoping for improvement ... certainly NOT cure. P.S. I have always said, "If it would just stop here." But it doesn't. Does it?


DEBORAH'S COMMENTS: But, hope is always there....Michael, before you talked to your doc, did you have expectations of what the Aricept would do? If so, where did the expectations come from? I'm trying to understand how we build our mental map of what we can expect from these medications --where we gather our info to make the mental map. What do you think?


MY REPLY: I have always believed that the "patient" (or caregiver in this case) has at least as much responsibility for understanding the illness, the medications, the precautions, the prognosis, etc ... as does the doctor. Both must be part of the team that makes the best possible decisions and makes the best possible use of the information available. So many people will reply, "I just do what the doctor told me." I say, "Question and understand. Challenge if necessary. Do not accept blindly." I have also heard, "It is just too confusing so I didn't bother." I say, "Bother! If you don't understand ask again. A good doctor will take the time to help you understand and/or send you in the direction of getting the extra help to understand that you need. Have someone help you understand. Don't just settle."

What I knew about Alzheimer's Drugs came from discussions with our doctors and study online. From the beginning, I knew that Aricept and Namenda would not CURE or REVERSE the dementia. I knew that it would help to slow it down so the quality of life would last for a little longer. I also knew that everyone reacts differently within the general pattern of things. Therefore, I was not so surprised when the medications gave Gregory a jump start of renewed "availability." 

And I agree, Deborah, it doesn't stop but the hope is always there. Even if it is the hope to get through one day, one success, one failure at a time. Hope to be strong, supportive, able for your loved one. And storng, supportive, and able for yourself.