Cure Alzheimer's Fund: Targeting Breakthrough Research

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

Written by Katie Barr Thursday, 29 April 2010 15:40

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!

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

Monday, 05 April 2010 10:36

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

Thursday, 01 April 2010 08:34

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

Wednesday, 31 March 2010 11:30

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!