News

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

With Our Venture Capitalist Approach, Cure Alzheimer’s Fund “Dares to Be Great”

The website Xconomy Boston has written a profile on one of our founders, Henry McCance, outlining our entrepreneurial approach to funding innovative researchers. Xconomy looks at how Cure Alzheimer’s Fund translated Henry’s expertise as a venture capitalist to the realm of medical research, which was sorely lacking a bold source of funding.

“McCance recalls researchers saying that the organizations that traditionally dole out the grants are so risk-averse that they don’t want to fund anything that has the slightest potential of failure. ‘We are forced to submit proposals which we almost already know the answer to,’ was their lament, McCance says. “Research that does get funded is akin to 1-yard plunge. There is no organization that is willing to throw us a 30 yard pass down the field.’”

Xconomy explains the ways McCance and other Cure Alzheimer’s Fund founders developed an alternative approach. They targeted visionaries in the field, brought in high-quality leadership, and kept a frugal culture to ensure funding going straight to research. The result – an unprecedented approach to push the boundaries of Alzheimer’s research.

The article, a great introduction to our entrepreneurial approach, can be read in full here.

Do you have any questions on our funding strategy? E-mail us your questions at info@curealz.org

Our Researchers in the News

Nature News article highlights Cure Alzheimer’s Fund researchers Stephen Strittmatter, Robert Malinow, and Sam Sisodia discussing conflicting results of Alzheimer's research and how Cure Alzheimer’s consortium hopes to unite researchers and move more quickly toward a cure.

Read the article, Key Alzheimer's findings questioned>

What does the Lilly drug failure tell us?

The recent Lilly Alzheimer’s drug failure, while disappointing, brings up critical issues around what is next in the “drug” pipeline and the validity of the Amyloid hypothesis.  An article on Bloomberg.com yesterday covers the story well.  Lilly Alzheimer's Setback Threatens Rivals' Prospects.

The article points to the weaknesses in Lilly’s trial. First, there is still no consensus that the target of their trial is the best solution. Analyst Les Funtleyder from Miller Tabak & Co. notes:

“The problem is that amyloid is still not the unanimous choice for what causes Alzheimer’s. If you don’t understand how the disease starts and operates, it’s going to be hard to find a cure or a treatment. That’s what we are up against.”

Furthermore, Rudy Tanzi, Cure Alzheimer’s Fund Research Consortium chairman, notes that the way in which Abeta was targeted by the Lilly drug was not optimal.

“the failure of the Lilly drug was due to the poor performance of the drug they used rather than the entire approach of controlling beta-amyloid. Gamma secretase has dozens of proteins it must cleave to have a healthy brain and a healthy body. You can’t hit that enzyme with a sledgehammer because it’s vital and has lot of different functions.”

While the drug failure is frustrating, we weren’t terribly surprised. See Tanzi’s write-up titled Novel Therapies for Alzheimer's Disease Based on Early Onset Genes which was prepared as Supplemental Information for Senate Special Committee on Aging Hearing in the Summer of 2008. He wrote:

LY450139(the Lilly drug) is a gamma secretase inhibitor (GSI) targeted at blocking the activity of gamma-secretase, an enzyme necessary for the production of A-beta. While this particular drug has done quite well recently proceeding all the way to phase III clinical trials, this class of drug has generally been shrouded with potential safety concerns. This is because the enzyme, gamma-secretase, is normally needed to process many other proteins beyond the APP. For example, gamma-secretase is required to processes the essential protein called Notch. When this event is blocked, the result can be skin cancer. Yet, the fact that Lilly’s candidate has made it all the way through to phase III trials would attest to this inhibitor’s safety.

That Dr. Tanzi was skeptical of the Lilly drug over two years ago should be proof enough that the current research strategy is too narrow-minded in its approach. A successful drug for AD will require one that 1. Is safe; 2. Gets into the brain; and 3. Has sufficient potency. With the hope of achieving this goal, Cure Alzheimer’s Fund is supporting research at UCSD and MGH on drugs called gamma secretase “modulators”, which lower amyloid beta protein levels without the safety issues of the gamma secretase inhibitor that just failed at Lilly.

This failure reaffirms the rising importance of better understanding the triggers behind Alzheimer’s. As Tanzi also says in the Bloomberg article,

“If the existing drugs don’t work, advances in genetics are giving researchers a growing list of targets to slow or prevent Alzheimer’s disease”

And this is our goal at Cure Alzheimer’s Fund. More research is needed to make sure we are driving toward a cure. We hope the Lilly trial sends a message to all those effected by this disease: better understanding of the cause will lead to better chances of finding a cure.

 

Great Recognition

MassGeneral Magazine’s August issue profiles the creation of Cure Alzheimers Fund and highlights the success of our venture capital approach. The article details the innovative work being done by Dr. Tanzi, such as the Alzheimer’s Genome Project, thanks to the bold investments of Cure Alzheimer’s.

In the years when the Alzheimer’s scientific community was focused on better understanding and exploiting the four known genes implicated in the disease, Dr. Tanzi was one of few researchers advocating for finding others. By design, CAF’s founders — who had spent their careers in venture capital, banking and real estate — had established that the organization would do away with the red tape and reams of paperwork required for most grant proposals. And that modus operandi has resonated with the thousands of other donors who give to CAF.

To read the rest of the article, click here.

For a more in-depth look at the Alzheimer’s Genome Project, read MassGeneral Magazine’s article, “Unforgettable Breakthroughs in Alzheimer’s,” in the same issue.

Sharing of Data Leads to Progress on Alzheimer’s

Congratulations to the collaborators and researchers of ADNI (Alzheimer’s Disease Neuroimaging Initiative). The New York Times reports the good progress of ADNI to “find biomarkers that show the progression of Alzheimer’s disease in the human brain”.

Cure Alzheimer’s Fund is a proud contributor of this effort. Read about our funding>

Read the story in the New York Times>

 

We Agree.

“Bottom line: research into Alzheimer’s—its cause(s), treatment, and cure—is alarmingly urgent and terribly underfunded.”

-Marty D. from her blog The Amazing Aging Mind

There is no doubt Alzheimer’s research needs more funding. And we agree with a lot of what Marty D. wrote in her recent blog about the Alzheimer's research paradigm, funding to find a cure, and clues from our genes. Check it out:

Paradigm Lost: Alzheimer’s, beta amyloid, fund-raising, and a taboo research topic?

Spinal Fluid Tests: Who Are They Really Good For?

A NYT article about the value of using spinal fluid tests to determine the presence of Alzheimer’s disease is optimistic and hopeful but maybe too much so.

In an article published yesterday, Gina Kolata writes “Researchers are finding simple and accurate ways to detect Alzheimer’s long before there are definite symptoms. In addition to spinal fluid tests they also have new PET scans of the brain that show the telltale amyloid plaques that are a unique feature of the disease.” And “Although the latest PET scans for Alzheimer’s are not commercially available, the spinal fluid tests are. So the new results also give rise to a difficult question: Should doctors offer, or patients accept, commercially available spinal tap tests to find a disease that is yet untreatable?”

The article raises a variety of complex subjects around early diagnostics. We have blogged about "early detection" issues recently and discussed the popular media topic of “is it good to know what you have before you can cure it?” story. We have commended the research community for the development of new early detection techniques and new categories to describe pre-clinical, early signs and full involvement phases of Alzheimer’s disease FOR RESEARCH PURPOSES ONLY.

One researcher not connected with the study is quoted in the NYT article as saying: “This (spinal fluid test) is what everyone is looking for, the bull’s-eye of perfect predictive accuracy.”

Good sound bite; not an accurate interpretation of the data in the paper to which the NYT article refers.

The study in Tuesday’s Archives of Neurology includes a limited number of patients, and would have to be carried out long enough to check whether the subgroup of cognitively normal subjects who were positive for the test later get AD. Otherwise, it would be too early to use this test as a sole diagnostic for AD. At this point, the data would only warrant potential use of the spinal tap test as a "differential" diagnostic to help diagnose AD in a patient already presenting with dementia, similar to how APOE4 gene testing is used now.

The use of brain scans and other biomarkers or physical indications of the presence of AD pathology is critically important for research into how AD pathology originates, progresses and ultimately how it can be stopped; but the clinical use of these biomarkers with the general population to predict or determine the presence of Alzheimer’s is premature.

As we have written before in this blog:

“It is so easy --- and we believe wrong --- to hail a fundamental advance in research as having immediate clinical benefits when there are none at this moment. So, the net effect is to tarnish an excellent approach to useful research that will ultimately help to bring relief to patients and their families with sensational and exaggerated claims or suggested impact.”

Articles like this draw considerable media attention and can give the general public the wrong impression that there is a clear and clinically appropriate way to diagnose Alzheimer’s.  Instead, this good research should be heralded for its contribution to understanding the disease and the significant role it will play in determining the path to a cure.

This study is hopeful and optimistic but more for the research value than for immediate help for AD patients.

Read the full piece in the NYT>

ABC News agreed with us. See the segment here>

New Keys to a Cure: The Importance of Oligomers.

New Scientist published an article on how recent breakthroughs in Alzheimer’s research are questioning longstanding explanations of the disease. The article, which notes the work of two Cure Alzheimer’s Fund researchers, emphasizes an issue we have been saying for years: we need to better understand the cause, not just attack the disease symptoms.

“Thanks to a new imaging techniques, the plaques [the most common indicator of Alzheimer’s] can now be seen in the brains of living people. Not only could this allow early diagnosis, it is helping overturn the long-standing orthodoxy over the causes of Alzheimer’s, and paving the way for effective treatments.

 

The article notes discoveries by Sam Gandy, funded by Cure Alzheimer’s Fund, proving a correlation between oligomers and cognitive problems in mice. Dr. Rudy Tanzi, a member of the Cure Alzheimer’s Fund Research Consoritum supports Dr. Gandy’s findings.

The study is coup de grace, says Rudolph Tanzi, an Alzheimer’s researcher at Harvest Medical School and Massachusetts General Hospital. “It finally shows exactly what all the previous data were pointing to but never directly showed – we can have a brain with no plaques but still have problems.”

If interested in the full article, email info@curealz.org.

 

 

A Flash of Genius Courtesy of the Alzheimer’s Reading Room

Bob DeMarco, the editor of the Alzheimer’s Reading Room, has written a great article on Dr. Rudy Tanzi. The article introduces Dr. Tanzi’s theory on abeta’s role in the human brain, which he describes as “a sudden flash of genius.”  He also writes about his frustration with underfunded research projects and failed drug trials. We cannot agree more!

Dr. Tanzi's new hypothesis "says what we need is the equivalent of a statin for the brain so you can dial it down but not turn it off.” The it being beta amyloid, A-beta.

“It means you don’t want to hit A-beta with a sledgehammer,” Dr. Tanzi said. “It says what we need is the equivalent of a statin for the brain so you can dial it down but not turn it off.”

A sudden flash of genius? Or another bridge to no where?

It is too early to tell. I like this way of thinking outside the box. It seems to me the answer will come from outside the box.

Read more the rest of the article here.

Make sure to check the Alzheimer’s Reading Room regularly. The website is an amazing resource for news on Alzheimer’s.

Bob DeMarco is the founder and editor of the Alzheimer’s Reading Room and the caregiver for his 91-year-old mother.

Q&A from July 22, 2010 Webinar

Thank you again to the attendees of our webinar. Below are the questions we received from participants with answers from Dr. Rudy Tanzi, as well as links to additional information. We have also posted the slides of the presentation here. If you would like to download the PowerPoint file, e-mail Katie Cutler at kcutler@curealz.org.

1.We know the disease process of Alzheimer’s starts long before the actual pathology and symptoms develop. With the growing knowledge of genes involved, wouldn't it be better to try the novel approaches in select individuals long before (say in their 50's) instead of those that have established Alzheimer's? It is disappointing (both to the researchers and the wider Alz community) to hear every time a study results are published, they come up with unsatisfactory results- Dimebon, Rember, Immunisation trials to name a few.

Yes, our goal is to use the genes to predict AD before it strikes and prevent the disease presymptomatically. I agree that it is not constructive to only focus on failed clinical trials of drugs that were not very good to begin with. Let’s focus on the next wave of therapies that have learned from these failures!

Note from Cure Alzheimer’s Fund: Check out more info on this in “Why the Drugs Don’t Work” and in “Sharing Data is Good But We Need to Better Understand Causes of the Disease”

I also wonder if other dementias - vascular/multi-infarct, mixed and frontotemporal dementias will respond to the treatments being developed for Alzheimer’s as the general consensus now appears to be mitochondrial dysfunction and neurotoxicity!

The frontal lobe dementias are based on tangle formation and tau protein abnormalities. So, drugs targeting abeta will most likely not be very helpful. This is why we also need anti-tangle drug programs.

2.What is the difference between genetic predisposition to Alzheimer's disease and familial predisposition to Alzheimer's?

The bottom line is that in familial early onset cases involving mutations in APP, presenilin 1 or presenilin 2, it is not so much predisposition as it is "causation". Any one of the ~200 mutations in these three genes guarantee Alzheimer's when inherited, usually before the patient turns 60 years old. In contrast, in late-onset AD (>60), the APOE4 gene variant increases susceptibility for AD usually between 60 and 80 (~3-fold if one parent transmits it, ~10-fold if both parents transmit it). So, this would be considered a gene variant that predisposes to AD but does not cause the disease with certainty the way the early-onset familial AD gene mutations do. Of course, you can also have familial late-onset AD and here we have found rare mutations in the ADAM10 gene that have strong effects on risk for getting the disease at about 72 years-old. In our Alzheimer's Genome Project, we have found 200 new AD gene candidates. We are currently scouring these genes to find the defects and determine whether they are causative like the early-onset familial AD gene mutations, or predisposing like the APOE 4 variant.

3.Given (as you have found) that beta amyloid has an antibiotic role in the brain, the "Alzheimer's vaccine" seemed to be the perfect Trojan Horse--wiping out beta amyloid and leaving the brain vulnerable to the agents that b-a were fighting off in the first place. You claim PBT2 takes this role of beta amyloid into account, leaving the fighting capacity of beta amyloid while removing the toxic "leftovers" of the fight. Is research also concerned about reducing the foreign cause of aggression in the brain--the agents that beta amyloid is designed to fight off? Is there perhaps an overabundance of these damaging bodies in Alzheimer's cases?

Yes, we are looking into what types of brain insults trigger the innate immune system to produce excess abeta. These insults could range from neurovascular insults, e.g. strokes or traumatic brain injury, to infections.  With regard to the latter, we are focusing on Chlamydia pneumoniae and candida albicans, given our and other’s findings.

Note from Cure Alzheimer’s Fund: For more info check out “Abeta May Have Beneficial Function as Part of the Innate Immune System

4.You said Dimebon was a failure without giving specifics of why it was a failure. From web articles, it's clear it was a failure because it did not improve memory. You also mentioned that another drug showed success (I think it was Bapi) in that it improved higher reasoning. There are plenty anecdotal accounts that Dimebon improved attention, social engagement and wit--functions that are regulated by the frontal cortex--the same area that affects higher reasoning. Why is one considered a success while the other is considered a failure for doing the same thing?

The official clinical trail results for both Dimebon and Bapi were negative in regard to cognitive improvement, which was the major primary endpoint measured for both drugs. However, in the case of Bapi, post-hoc stratification of APOE4-positive versus APOE4-negative patients showed that the latter group had some benefit. So, in the ongoing Bapi trial, I believe they included the APOE4 stratification as a primary endpoint and there could again be a positive result. The major caveat is that in the first trial and beginning of the current trial, APOE4-positive patients also suffered from more adverse side effects, including vasogenic edema (inflammation) of the brain and in some cases cerebal micro-hemorrhage. So the dose of Bapi in the ongoing trial had to be lowered for the APOE4-positive patients. We will have to wait and see if Bapi still has benefits for Cognition. Let’s hope so.

Note from Cure Alzheimer’s Fund: For more info check out “The Success Stories of Tomorrow” and “Why Don’t the Drugs Work”

From Twitter:

1.@CureAlzheimers How are Alzheimer's and Chronic Traumatic Encephalopathy different?

They are entirely different. However, any brain trauma can theoretically increase downstream risk for AD. I don’t know of any data specifically linking chronic traumatic encephalopathy to AD.

2.@CureAlzheimers Opinions on the action on the alpha-7 nAch receptor in Alzheimer’s?

These drugs have strong potential for cognitive enhancement, perhaps even beyond that of current drugs on the market and maybe even working well in concert with each other. However, they would most likely just be treating the symptoms rather than the actual disease. We would certainly welcome their appearance!

Thank you again for attending our webinar! To stay up-to-date on our work, follow us on twitter at twitter.com/curealzheimers or like us on facebook at facebook.com/curealzheimers