News

Find updates on the work of our researchers here, as well as news about recent advances in Alzheimer's science, funding and awareness.

Cure Alzheimer's Fund Awards Grant to University of Colorado School of Medicine

Boston – Cure Alzheimer’s Fund recently awarded Dr. Nicholas Seeds, with the University of Colorado School of Medicine, a $100,000 grant for novel research on Alzheimer’s disease, which affects 5.2 million Americans and their families and is the most common cause of dementia in the elderly.

“This research has the potential to unlock a new understanding of the causes and risk factors for Alzheimer’s disease,” said Tim Armour, President and CEO of Cure Alzheimer’s Fund. “It could bring us a step closer to ultimately stopping or even reversing its effects.”

The grant will allow Seeds’ lab to continue research on neuroserpin, a protease inhibitor in the brain that is a possible contributor to the onset of Alzheimer’s.  The lab’s research on mice shows that the deletion of the neuroserpin gene can lead to a reduction of Amyloid-Beta, a protein in the brain that is commonly linked to Alzheimer’s disease, and may result in restoration of normal cognitive behavior.  Most importantly, Seeds aims to identify small molecules that block neuroserpin. The goal is to create Alzheimer’s therapeutics for future patient studies.

“With university budgets stretched thin, the Fund’s support is critical in helping further this important research on this devastating disease,” said Seeds, a Professor of Biochemistry and Molecular Genetics at the Colorado medical school.

Cure Alzheimer’s Fund has no endowment and passes funds raised directly to selected research. The Fund has no financial or intellectual property interest in the research funded, and will make known the results of all funded research as soon as possible. Over the past ten years the federal government’s investment in Alzheimer’s research and education has decreased. Since it’s inception in 2004, Cure Alzheimer’s Fund has raised more than $15 million, investing all of it directly into research.

“Research is key to finding a cure and better treatments for Alzheimer’s disease,” said Armour.  “With the advances in technology over the past 10 years, great strides have been made in Alzheimer’s research and we are on the cusp of major breakthroughs. Cure Alzheimer’s Fund believes the pioneering work of the University of Colorado School of Medicine researchers and others could bring us one step closer to our goal of finding a cure.”

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About Cure Alzheimer's Fund

Cure Alzheimer's Fund™ is a 501c3 public charity whose mission is to fund research with the highest probability of slowing, stopping or reversing Alzheimer's disease. Cure Alzheimer’s Fund is characterized by a venture approach to philanthropy, which targets funding to specific research objectives. All expenses and overhead is paid for by its founders and all contributions go directly to research. The Foundation has no financial or intellectual property interest in the research funded, and will make known the results of all funded research as soon as possible. Cure Alzheimer’s Fund is a national organization with offices in Boston and Pittsburgh. For more information, visit www.curealzfund.org.

About University of Colorado School of Medicine

Faculty at the University of Colorado School of Medicine work to advance science and improve care. These faculty members include physicians, educators and scientists at University of Colorado Hospital, The Children’s Hospital, Denver Health, National Jewish Health, and the Denver Veterans Affairs Medical Center. Degrees offered by the School of Medicine include doctor of medicine, doctor of physical therapy, and masters of physician assistant studies. The school is located on the Anschutz Medical Campus, one of four campuses in the University of Colorado system.

 

Cure Alzheimer's Fund Chairman and Co-Founder Jeff Morby at Miliken Conference: We Need a National Strategy to Beat Alzheimer's

 

Jeff Morby, Chairman and co-founder of Cure Alzheimer’s Fund, was a featured panelist at the Milken Global Conference in Los Angeles on Wednesday, April 28. The presentation was titled, “Alzheimer’s Disease: Meeting the Challenges of an Aging Society”.  Click here to watch Jeff, Harry Johns, the President and CEO of the Alzheimer’s Association and Greg Simon, the Senior Vice President for Worldwide Policy for Pfizer, address the need for a national strategy to battle the disease.

 

Milken Panel Concludes National Strategy is the Only Way to a Cure

Our very own Jeff Morby, Chairman and co-founder of Cure Alzheimer’s Fund, was a featured panelist at the Milken Global Conference in L.A. this week where he led the charge, calling for a national strategy for a cure.

The presentation titled, “Alzheimer’s Disease: Meeting the Challenges of an Aging Society,” also featured fellow industry heavyweights Harry Johns, President and CEO of the Alzheimer’s Association and Greg Simon, Senior Vice President for Worldwide Policy, Pfizer. Discussion focused on building a climate for a cure, from public awareness to government to private investment. All agreed upon one critical step that must be taken -- the creation of a national strategy for a cure by 2020. Click here to view the video.

Simon kicked off the discussion noting that to discuss the process of finding a cure is depressing; it is expensive and probably years ahead of us. But the point driven home by all three gentlemen is that we will get there a lot faster if we build a national consensus around the importance of doing so now.

On the same “aspirational” theory as putting a man on the moon, stopping polio or any of the other campaigns that were once looked upon as naively ambitious, Morby argued that a national drive to overcome Alzheimer’s is necessary to muster the resources to do the job in time to head off the “silver tsunami” that will overwhelm our healthcare resources. Almost half of people over 85 have the disease, and in 2010 the Medicare and Medicaid expenses alone were $186 billion. That number will only go higher exponentially the longer we are unable to control the onset of the disease.

So hooray for the leaders of Cure Alzheimer’s Fund, the Alzheimer’s Association and a senior representative of a Pharma for the courage to be bold and begin the drum beat for a national strategy to end Alzheimer’s disease!

APOE and Alzheimer’s Disease

Co-chaired by three members of CAF’s Research Consortium—Drs. David Holtzman, Sam Sisodia and Rudy Tanzi—participants included all the other members of the Research Consortium (except Virginia Lee, who had a prior commitment) and several invited guests whose records of research include valuable insights into this relationship. The guests were Michael Brown, MD, and Joachim Herz, MD, Southwestern Medical School; Alan Tall, MD, Columbia University; Karl Weisgraber, Ph.D., Gladstone Institute, University of California, San Francisco; and Cheryl Wellington, Ph.D., University of British Columbia.

Abeta May Have Beneficial Function as Part of the Innate Immune System

The Amyloid-beta protein is a key contributor to Alzheimer’s pathology and the prevailing theory has been that Abeta has no function other than as a waste product created by the brain. It is acknowledged by most researchers to be a key “bad guy” in Alzheimer’s pathology.

Why don’t the drugs work?

A spate of headlines recently dimmed hopes for a wonder drug to fight Alzheimer’s disease. We know the existing drugs used to treat Alzheimer’s patients, including Aricept, Namenda and others, provide only modest symptomatic relief but do not treat the root pathology of the disease. Let’s look at three new drugs that attempted to get at the causes of the disease but failed. We’ll look at the “bad news,” comment on why they failed and then look at what’s in the pipeline signaling better news.

Help us win $250,000 for Alzheimer’s research -- Vote today!

By Tim Armour

Every 70 seconds, another American is diagnosed with Alzheimer’s -- that’s over 5 million Americans suffering from this devastating disease each and every day.

But today, we have the unique opportunity to perform one simple act that could make a big difference in the fight against Alzheimer’s.

Through the Pepsi Refresh Project, Cure Alzheimer’s Fund has the chance to win a $250,000 grant that would fund the groundbreaking research that will help us find a cure to this destructive disease.

But we need your help to make this funding a reality!

Just visit www.refresheverything.com/curealzheimers and click “vote for this idea.” Then register with Pepsi Refresh by entering your email and password so you can easily vote every day!

We started Cure Alzheimer's Fund because we want to find a cure now. We’re the only organization with a roadmap to a cure -- we just need the funding to make it a reality. The Pepsi Refresh grant can make a big difference, bringing us that much closer to a cure.

What you do right now really matters. Please send the link to everyone you know and ask them to join you in voting for Cure Alzheimer’s Fund. It’s a very small step, but one that could mean the world of difference to Alzheimer’s sufferers everywhere.

Voting runs now through April 30th, and remember, you can vote once a day so vote early and vote often!

The Good News

By Tim Armour

From the new findings about oligomers, many supported by Cure Alzheimer’s Fund, we know a lot more about the toxicity of the Abeta42 oligomers and how that affects the neural synapses. None of these first or second generation drugs were aimed at stopping Abeta 42 aggregation or oligomerization; nor were any of them directed toward protecting the neural synapses. They were more directed toward stopping Abeta production altogether through modifying or eliminating steps in the production process.

Furthermore, from new and potentially paradigm-breaking research also sponsored by Cure Alzheimer’s Fund, we now know that Abeta42 may be an integral part of the innate immune system. In other words, it is actually good for fighting off bugs in our system, particularly in the brain, and to develop drugs to stop its production completely or dramatically reduce it would be a big mistake.

Third, Cure Alzheimer’s Fund is supporting new research on more promising approaches to the regulation of Abeta. One of these tracks is the exploration of a whole new class of “gamma secretase modulators” which are safe and more potent that those used in Flurizan or other failed drug tests. A second is experimentation with drugs that specifically target one step of the cholesterol pathway, acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, reducing generation of toxic Aβ peptide in cells and in an animal model of AD. And finally, other research being funded by Cure Alzheimer’s Fund is screening all approved (and therefore safe) drugs in the entire human pharmacopeia to see which ones lower Abeta levels.

Were those first and second generation drugs “failures?” If measured by their ability to stop the disease or provide immediate relief to patients -- then yes -- and that is clearly what is most important. However, in their failure, they have helped to correct the direction along the “Abeta trail” and help us focus on more effective therapeutic approaches.

Where do we go from here? One conclusion is to keep following the Abeta trail. It is increasingly clear that it is the seminal actor in Alzheimer’s pathology.

Second, primary therapeutic targets based on this information should be focused on at least three approaches:

  • Continue to find ways to “modulate” the production of Abeta to prevent over-production, but allow that amount that is actually helpful or protective to continue to be made and safely deployed;
  • Find ways to prevent the “oligomerization” of the Abeta42 peptide in its most toxic forms.
  • Continue to explore the Abeta/neural synapse relationship to maximize Abeta’s potential protective capability and reduce its toxicity.

This will require heeding the lessons from what we are learning from genetics, now having identified over 100 candidate Alzheimer’s genes for more study about how they affect risk for the disease, what the first and second generation drugs have taught us, and aggressive exploration of newer perspectives on the role of Abeta42 and how it can be modulated safely for effective reduction or elimination of risk for Alzheimer’s.

It is a challenging task that will require significantly increased resources. But the way forward is clear; follow the Abeta trail.

 

The Success Stories of Tomorrow

By Tim Armour

Yesterday I discussed the scientific community’s profound disappointment in the failure of three different, high-profile Alzheimer’s drugs. But despite their inabilities to get at the root of this disease, they have played an important role in what will likely be the success stories of tomorrow.

First, all of these drugs addressed what most researchers believe is the key “bad guy” in Alzheimer’s disease pathology --- the small protein (peptide) Abeta, and particularly it’s genetic variant, Abeta42 (that means there are 42 molecules of the Abeta variant in this species instead of the more frequent 40 or other conformations). The Abeta trail is a long and winding one which first pointed to Abeta42 as the substance which formed the plaques in the brain that somehow extinguished brain cell communication. Recently, the Alzheimer’s research field has moved to a more sophisticated understanding of how Abeta42 does its work. It is now increasingly thought to be toxic only or primarily in its aggregated, clumped or “oligomer” form. These oligomers are now seen to be forming at or near the neurons in the brain responsible for the neural communication that enables acquisition of new information and creation of memory.

The science of all of this is complicated and rapidly evolving, but the essence is that the focus of the cause of the disease has moved for the most part from the plaques to the formulation of the Abeta peptide itself and its coalescing into the more toxic oligomers.

One great challenge to the rapid evolution of the understanding of the causes of the disease is the assault on the “Abeta” thesis because of the failure of these drugs to stop the disease. If their target was the control or elimination of Abeta42 and they failed, the reasoning goes, maybe Abeta42 is the wrong target.

Not so fast.

1). The early drugs and this second “failed” generation have focused on trying to stop Abeta42 from forming in the first place. Flurizan, for example, was designed to block Abeta42 production by modulating an enzyme important to Abeta42 creation (“gamma secretase”). The drug failed because it was not potent enough to affect change in Abeta levels; stronger doses delivered to human patients created fatal side effects. That means that the theory of the “mechanism of action” is probably not wrong, but this particular drug compound and its near relatives failed to achieve the appropriate risk/effectiveness balance.

2). Bapineuzumab was based on Abeta immunotherapy (passive immunization) in which antibodies targeting Abeta are injected intravenously into AD patients. While initial trial data looked promising, more recent trials showed that, once again, high enough does of the drug to be effective caused dangerous side effects for patients. A further complication is that the drug appeared to be slightly more effective in the group of patients which do NOT carry the best known and most prevalent Alzheimer’s gene, APOE4. The hurdles to re-balancing this particular family of compounds will prove to be a great challenge for Johnson and Johnson’s Alzheimer’s unit.

3). Finally, Dimebon. A strange story indeed, and a heartbreaking one for patients and their families who read about the promise of this “wonder drug.” While the Dimebon “method of action” against Alzheimer’s pathology is not yet apparent, what is clear is that based on the rigorous (but hopeful!) US trials, the drug does not work. It is safe, but completely ineffective. Some who know this story more intimately suspect that the original Russian data was misleading; others simply don’t know what to make of the disparity. In any case, there appears to be little or no hope for this drug as an effective therapy against Alzheimer’s disease.

What does all this tell us? Aside from dashed hopes and ruined companies, what it does NOT tell us is that the Abeta trail is a wild goose chase. Not at all.

So where does this leave us? Stay tuned tomorrow for the good news!

Why Don't the Drugs Work

By Tim Armour

A spate of headlines recently dimmed hopes for a wonder drug to fight Alzheimer’s disease. We know that the existing drugs used to treat Alzheimer’s patients including Aircept, Numenda, and others provide only modest symptomatic relief but do not treat the root pathology of the disease.

In a series of posts this week, we’ll look at three new drugs which attempted to get at the causes of the disease but failed. We’ll look at the “bad news,” comment on why they failed and then look at what’s in the pipeline signaling better news.

1). The first high profile failure was Flurizan (tarenflurbil) by Myriad Genetics. A June 30, 2008 report by Myriad CEO Peter Meldrum concluded, “We are disappointed that Flurizan failed to achieve significance and we will now discontinue development of this compound.” Womp went Myriad’s stock and the hopes of millions as a result of this $60 million “failure.”

2). The second is the disappointing results of trials for bapineuzumab (acronym for “Beta Amyloid Peptide (I) Neutrali Z ing (U) M onoclonal Antibody) by pharmaceutical partners Elan and Wyeth. The companies tried several variations of doses of this drug, but experienced safety issues at the higher, more effective doses because of the presence of vasogenic edema in some of the study’s patients. “Bap’s” development has now been taken over by Johnson and Johnson’s Janssen Alzheimer’s Immunotherapy unit which announced, on March 17th, an extension of current trials with no announcement about results of those trials until 2012.

3). Third is the very recent spectacular rise and fall of Dimebon, a drug developed in Russia as an antihistamine and brought to the US after extensive review of the Russian trials as an Alzheimer’s drug. Initial data was, in essence, “too good to be true” in its apparent ability to lower Abeta in the brain and cause a decrease in Alzheimer’s symptoms. Subsequent trials in the US by the drug’s US licensee, Medivation and its partner Pfizer, could not replicate this “too good to be true” data. In fact, US-based trials, known as CONNECTION, showed no benefit whatsoever. The day the results of these US trials were announced, March 3, 2010, Medivation lost 70% of its value.

We all know that drug making is a high risk business. The pharmaceutical companies tell us this all the time, supporting what many people regard as very high prices on the fewer successful drugs in order to support the risk-taking. Some of this is absolutely true; but without getting into the economics of this issue here, let’s look at the science.

Why did these drugs fail, and in their failure can they help us improve on the next generation of therapies?

Stay tuned for the answers to those questions tomorrow, here on the blog.