Gleevec for Alzheimer's, et al

February 22, 2011

An altered version of the cancer drug Gleevec could form the basis of a new

class of drugs that block the development of brain-damaging plaques in

Alzheimer's disease, U.S. researchers said on Wednesday.

The key lies in an enzyme that triggers the production of beta amyloid plaques,

one of the hallmarks of Alzheimer's. Gleevec, now used to treat chronic myeloid

leukemia, blocks this gamma-secretase activating protein.

" Our findings reveal that gamma-secretase activating protein is a potential

target for a new class of anti-amyloid therapies, " said Greengard, winner

of the 2000 Nobel Prize for research into how neurons communicate, who worked on

the study published in the journal Nature.

The latest study, led by Gen He, a researcher in Greengard's lab, shows that

this protein dramatically increases the production of beta amyloid, and blocking

the protein in genetically engineered mice kept Alzheimer's brain plaques from

developing.

Greengard said Gleevec clears too quickly from the brain to prevent Alzheimer's

disease on its own, but he believes drug companies could find ways to make it

active in the brain longer.

" The development of compounds that work like Gleevec, but have the ability to

pass the blood-brain barrier and target gamma-secretase activating protein could

revolutionize the treatment of this disease, " Greengard said in a statement.

He said Gleevec could be modified chemically so it does not get pumped out right

away. " I'm sure when our paper is published, a number of pharmaceutical

companies will try to do just that, " he said.

MORE TARGETED APPROACH

Greengard said the gamma-secretase activating protein is more targeted than

other Alzheimer's drugs in development that target gamma-secretase. That is

because it does not interfere with Notch, a vital cell signaling pathway that

plays a pivotal role in the development of blood-forming organs and the immune

system.

http://tinyurl.com/38z2a93

*******************************

GENERATING STEM CELLS

Mouse skin cells have been directly reprogrammed to become beating heart cells.

The method used could be safer and more efficient than previously developed

techniques, which can take weeks, yield low numbers of cells and may generate

stem cells with the potential to cause cancer.

Sheng Ding at the Scripps Research Institute in La Jolla, California, and his

team found a short cut that bypasses the stem-cell stage. The researchers

briefly exposed the skin cells to three genes often used in cellular

reprogramming and grew the cells in a special medium to avoid the generation of

stem cells. Then, treatment with a cocktail of cardiac growth factors coaxed the

cells into becoming beating heart cells. The method took just 11–12 days to

generate the first beating cells and yielded more cells than previous direct

cardiac cell reprogramming techniques.

http://tinyurl.com/4tfm88e

*****************************

Since A Fib has been a subject for discussion recently, I have found this to be

of particular interest.

Atrial fibrillation (AF) is a common problem around the world. In the US, 15% of

people over the age of 70 years have AF. Early estimates suggested that this

translated into roughly 2.2 million Americans with the disease. More recent

estimates suggest that the number of people with AF currently exceeds 6 million

and will rise to 10 million by 2030. In Europe and parts of Asia, the incidence

of AF is approximately 7% in patients over the age of 65. Even at the lower end

of estimates, the annual economic impact exceeds US$6.6 billion in the US alone.

More importantly, the presence of AF is associated with a twofold increase in

mortality in the general population and is even higher in patients with

congestive heart failure.

Perhaps the most alarming feature of AF is its association with stroke. AF is

the second leading cause of stroke in the US and is responsible for at least

75,000 to 88,000 strokes each year. Strokes caused by AF tend to be more

devastating, and AF accounts for up to 30% of all strokes in the elderly.Stroke

is the third leading cause of death in the US; therefore, AF is a measurable

contributor to the nation's mortality. In developing countries with younger

populations, the incidence of AF is lower than in the US but the use of

anticoagulation is also lower and thus the incidence of stroke is substantially

higher. As the population of all societies continues to age, the magnitude of

this problem will continue to increase worldwide.

Two strategies exist to treat AF: rhythm control and rate control. Although

medical therapy has had limited success in sinus restoration, randomized,

controlled trials of medical therapy have not demonstrated a survival advantage

for either type of treatment strategy.

Catheter and surgical ablation techniques have evolved and seem to achieve

higher rates of freedom from AF. Currently, all patients with a history of AF

undergoing cardiac surgery should be considered for treatment of AF. For lone AF

(that is, AF with no overt structural heart disease), the indications are not as

clear. Generally, symptomatic patients with medically refractory AF should be

considered for intervention. Catheter ablation is usually the first or second

therapy considered. For patients in whom catheter ablation fails, or is likely

to fail, surgery offers a chance for cure. Below, the rationale for surgery is

described in a framework of historical procedures.

http://tinyurl.com/4fypz9s

*****************************

FYI,

Lottie Duthu

February 22, 2011

That is completely amazing to me because when I was taking Gleevec I felt

like I had Alzheimers. Obviously everyone has a somewhat different reaction

to any given drug of course. What a great blessing it would be if Gleevec

blocked Alzheimers from progressing.

This is fascinating. I also read a study that showed Gleevec could actually

reverse the progression of scleroderma. My sister has scleroderma and I told

her she should ask her doc about it. He told her there were more studies

underway, as of right now it hadn't been studied enough for him to prescribe

it. I'm watching the course of events very closely!

Many thanks to you as always dear Lottie for keeping us all up to date.

On Mon, Feb 21, 2011 at 10:31 PM, Lottie Duthu <lotajam@...> wrote:

> An altered version of the cancer drug Gleevec could form the basis of a new

> class of drugs that block the development of brain-damaging plaques in

> Alzheimer's disease, U.S. researchers said on Wednesday.

> The key lies in an enzyme that triggers the production of beta amyloid

> plaques, one of the hallmarks of Alzheimer's. Gleevec, now used to treat

> chronic myeloid leukemia, blocks this gamma-secretase activating protein.

>

> " Our findings reveal that gamma-secretase activating protein is a potential

> target for a new class of anti-amyloid therapies, " said Greengard,

> winner of the 2000 Nobel Prize for research into how neurons communicate,

> who worked on the study published in the journal Nature.

>

> The latest study, led by Gen He, a researcher in Greengard's lab, shows

> that this protein dramatically increases the production of beta amyloid, and

> blocking the protein in genetically engineered mice kept Alzheimer's brain

> plaques from developing.

>

> Greengard said Gleevec clears too quickly from the brain to prevent

> Alzheimer's disease on its own, but he believes drug companies could find

> ways to make it active in the brain longer.

>

> " The development of compounds that work like Gleevec, but have the ability

> to pass the blood-brain barrier and target gamma-secretase activating

> protein could revolutionize the treatment of this disease, " Greengard said

> in a statement.

>

> He said Gleevec could be modified chemically so it does not get pumped out

> right away. " I'm sure when our paper is published, a number of

> pharmaceutical companies will try to do just that, " he said.

>

> MORE TARGETED APPROACH

>

> Greengard said the gamma-secretase activating protein is more targeted than

> other Alzheimer's drugs in development that target gamma-secretase. That is

> because it does not interfere with Notch, a vital cell signaling pathway

> that plays a pivotal role in the development of blood-forming organs and the

> immune system.

>

> http://tinyurl.com/38z2a93

>

> *******************************

>

> GENERATING STEM CELLS

>

> Mouse skin cells have been directly reprogrammed to become beating heart

> cells. The method used could be safer and more efficient than previously

> developed techniques, which can take weeks, yield low numbers of cells and

> may generate stem cells with the potential to cause cancer.

>

> Sheng Ding at the Scripps Research Institute in La Jolla, California, and

> his team found a short cut that bypasses the stem-cell stage. The

> researchers briefly exposed the skin cells to three genes often used in

> cellular reprogramming and grew the cells in a special medium to avoid the

> generation of stem cells. Then, treatment with a cocktail of cardiac growth

> factors coaxed the cells into becoming beating heart cells. The method took

> just 11–12 days to generate the first beating cells and yielded more cells

> than previous direct cardiac cell reprogramming techniques.

>

> http://tinyurl.com/4tfm88e

>

> *****************************

>

> Since A Fib has been a subject for discussion recently, I have found this

> to be of particular interest.

>

> Atrial fibrillation (AF) is a common problem around the world. In the US,

> 15% of people over the age of 70 years have AF. Early estimates suggested

> that this translated into roughly 2.2 million Americans with the disease.

> More recent estimates suggest that the number of people with AF currently

> exceeds 6 million and will rise to 10 million by 2030. In Europe and parts

> of Asia, the incidence of AF is approximately 7% in patients over the age of

> 65. Even at the lower end of estimates, the annual economic impact exceeds

> US$6.6 billion in the US alone. More importantly, the presence of AF is

> associated with a twofold increase in mortality in the general population

> and is even higher in patients with congestive heart failure.

>

> Perhaps the most alarming feature of AF is its association with stroke. AF

> is the second leading cause of stroke in the US and is responsible for at

> least 75,000 to 88,000 strokes each year. Strokes caused by AF tend to be

> more devastating, and AF accounts for up to 30% of all strokes in the

> elderly.Stroke is the third leading cause of death in the US; therefore, AF

> is a measurable contributor to the nation's mortality. In developing

> countries with younger populations, the incidence of AF is lower than in the

> US but the use of anticoagulation is also lower and thus the incidence of

> stroke is substantially higher. As the population of all societies continues

> to age, the magnitude of this problem will continue to increase worldwide.

>

> Two strategies exist to treat AF: rhythm control and rate control. Although

> medical therapy has had limited success in sinus restoration, randomized,

> controlled trials of medical therapy have not demonstrated a survival

> advantage for either type of treatment strategy.

>

> Catheter and surgical ablation techniques have evolved and seem to achieve

> higher rates of freedom from AF. Currently, all patients with a history of

> AF undergoing cardiac surgery should be considered for treatment of AF. For

> lone AF (that is, AF with no overt structural heart disease), the

> indications are not as clear. Generally, symptomatic patients with medically

> refractory AF should be considered for intervention. Catheter ablation is

> usually the first or second therapy considered. For patients in whom

> catheter ablation fails, or is likely to fail, surgery offers a chance for

> cure. Below, the rationale for surgery is described in a framework of

> historical procedures.

>

> http://tinyurl.com/4fypz9s

>