Alzheimer's vaccine works on mice: Japan scientist + CANCER ARTICLE

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It's a far cry from mice to men but hope ever springs.

http://health./news/173545

Alzheimer's vaccine works on mice: Japan scientist

March 28, 2007 11:49:28 PM PST

Japanese scientists have developed an oral vaccine for Alzheimer's

disease that has proven effective and safe in mice, the director of a

research institute behind the project said on Thursday.

The team is preparing to move to small-scale clinical trials in humans,

possibly this year, said Takeshi Tabira, director of the National

Institute for Longevity Sciences in Aichi, central Japan.

" We hope the Phase I trials go well " , Tabira said. " Animals are able to

recover their functions after developing symptoms, but humans are less

able to do so. It may be that this only works in the early stages of the

disease, when symptoms are light "

When administered to mice suffering from the disease, which causes

dementia and is currently incurable, the vaccine reduced the amount of

amyloid plaques in the brain and improved mental function.

Amyloid plaques are believed to be at the root of Alzheimer's -- a

growing problem for aging populations around the world. The disease

affects five million in the United States alone, the Alzheimer's

Association said in a report last week.

The treatment did not cause inflammation or bleeding in the brains of

the mice, Tabira said.

The vaccine is made by inserting amyloid-producing genes into a

non-harmful virus. When taken orally, the virus stimulates the immune

system to attack and break down the amyloid proteins in the brain,

Tabira said.

The treatment was tested on 28 mice genetically modified to develop

Alzheimer's disease. Half the animals were given a dose of the vaccine

at the age of 10 months, while the control group were not treated.

Three months later, tests showed mental function in the treated mice had

returned to levels close to those before they developed Alzheimer's

symptoms.

U.S. drugmaker Wyeth and its Irish partner Elan Corp have an Alzheimer's

vaccine called ACC-001 in early stage human trials.

The Japanese research, carried out in conjunction with scientists at

Nagoya University and others, is to be published by the Federation of

American Societies for Experimental Biology in July

http://www.signs-of-the-times.org/articles/show/129460-Cancer+therapy%3A

+When+all+else+fails%3F+Or+maybe+try+this+first.

http://www.newscientist.com/article/mg19325973.800-cancer-therapy-when-a

ll-else-fails.html

Cancer therapy: When all else fails

* 28 March 2007

* Exclusive from New Scientist Print Edition. Subscribe

<http://www.newscientist.com/subscribe.ns?promcode=nsarttop> and get 4

free issues.

* Geddes

Lawrence Burgh has a sober outlook on life. A 48-year-old physician

whose career has centred on treating seriously ill patients, Burgh was

diagnosed with cancer in December 2006. Yet despite his clinical

experience, he has taken an extraordinary step to try to rid himself of

his illness, a step many would consider to be a medical heresy.

Burgh is one of a growing number of patients who have been dosing

themselves with a simple laboratory chemical that has never before been

used to treat cancer in people. Most are doing so without the help of

doctors, and none is enrolled in any systematic clinical trial of the

substance. Instead, they are buying it over the internet, and sharing

their experiences of it in online chatrooms. For them, the unlicensed,

untested drug represents their last best chance of survival.

That's not the way cancer specialists see it. For them, the activities

of Burgh and those like him are indicative of what could become a

dangerous new trend, in which groups of seriously ill people get

together online to discuss, source and try untested drugs whose safety

and efficacy is uncertain.

The drug in this case, known as DCA, is a widely available chemical that

cannot be patented. In basic laboratory tests and experiments in rats it

has shown promise as an anti-cancer agent, but in people it may yet show

side effects that could further damage the lives of people who take it.

Scientists investigating the potential of DCA as a cancer treatment fear

that any deaths or injury caused by its premature, unregulated use could

damage their work - and the welfare of patients far into the future.

Burgh's quest to cure himself began last month, shortly after he was

told the cancer in his thigh had spread to his lungs. " My prognosis is

very poor, " he says. " Standard chemotherapy would give me only a slim

chance of survival at five years. " So he turned to DCA, after reading

about the promising lab experiments in New Scientist (20 January, p

<http://www.newscientist.com/channel/health/mg19325874.700> 13).

" Standard chemotherapy would give me only a slim chance of survival at

five years "

DCA, or dichloroacetic acid, is an analogue of acetic acid in which

chlorine atoms replace two of the three hydrogen atoms on the methyl

group. Because it is a corrosive acid, it must be " buffered " to damp

down the acidity, and it is usually administered as sodium

dichloroacetate.

In January, a study by Evangelos Michelakis and his colleagues at the

department of medicine at the University of Alberta in Edmonton, Canada,

suggested that DCA could shrink several types of tumour in rats, by

exploiting a previously ignored metabolic pathway in the cell (see " How

DCA could affect cancer " , below). " I was intrigued by the proposed

mechanism, " says Burgh (not his real name; this article uses a pseudonym

to protect his privacy). " The biochemistry made sense to me. I

subsequently read dozens of articles and abstracts on DCA before I

decided I wanted to try it. "

On 27 February, he self-administered his first dose, and for the next

month took DCA twice a day, monitoring his blood and urine for signs of

any problems, and visiting his oncologist, who was aware of what he was

doing, once a week.

Because DCA is not an approved drug in the US, the UK or anywhere else,

Burgh had to find his own supply. Using his contacts he obtained raw

DCA, then asked a chemist friend to buffer it and check its purity.

Burgh is not alone in his attempts to procure the drug. Already, within

weeks of Michelakis's paper being published, a substantial online

community has grown up, largely centred on the website

www.thedcasite.com which declares itself to be a gateway for information

on DCA. At least eight of the individuals who have posted contributions

on the site's chatroom, including Burgh, claimed to be taking DCA or

giving it to a close relative. By 21 March, the chatroom had 135 active

members - most of them from the US, Canada, the UK and Australia - plus

posts from numerous unregistered users, many swapping tips on how to get

hold of DCA, how to prepare the chemical for human consumption, and what

supplements they should be taking to minimise side effects.

" This is pretty much a new phenomenon, " says Kate Law, director of

clinical trials at research charity Cancer Research UK. " There has

always been an industry for vulnerable people, but the magnitude of it

has multiplied exponentially. The internet has changed the world for

people who are looking for miracles. "

Michelakis himself warns that people taking DCA could do themselves

serious harm. The chemical is known to increase the risk of nerve damage

in people who have been given it in clinical trials for other reasons.

It may also cause liver damage and interact with existing anti-cancer

drugs in unexpected ways. " Since many anti-cancer drugs are neurotoxic,

these interactions could be fatal, " Michelakis says. Worst of all, he

says, if patients are taking DCA outside clinical trials, such damaging

side effects may go unrecorded.

Desperate measures

Yet there are many desperate patients prepared to take this risk.

Michelakis says his department gets thousands of emails from people

saying they have nothing to lose, but that's not how he sees it. " Of

course you've got something to lose, " he says. " There are many cases of

people being told 'you've only got a month to live', and a month later

they're still alive. If you take DCA, it may not work, you could still

have the cancer, and you'll be paralysed. "

Despite such warnings, people are continuing to hunt down details of

potential suppliers of DCA. " I have been getting three to four calls a

day, " says Steve Grossman, manager of J. E. Pierce Apothecary in

Brookline, Massachusetts. " I've had calls from pretty much the whole of

the northern hemisphere now, plus Africa, the Middle East and south-east

Asia. Mostly it is people with end-stage cancer, who have already gone

through everything medicine had for them. " Grossman says he will not

dispense DCA to anyone unless he sees a prescription from a doctor - and

no one has yet provided one.

Because DCA has never been approved as a drug for human use, the sale of

pharmaceutical-grade DCA, which has been sterilised, purified and had

its pH adjusted, is tightly controlled. In the US, a doctor can only

prescribe it if they have already applied for an Investigational New

Drug (IND) number from the Food and Drug Administration for its

compassionate use in a seriously ill patient, or in a clinical trial.

Doctors in Canada must gain permission from their provincial college of

physicians and surgeons, while companies who supply it to doctors in the

UK must inform a national regulatory agency.

As word gets around that people are buying DCA to use as a drug,

suppliers of the chemical are clamping down for fear of breaking the

law. However, despite these restrictions, people are still acquiring it.

Thedcasite.com <http://www.Thedcasite.com> shows at least 34 people

have got hold of DCA - either through doctors, or by obtaining raw

laboratory-grade DCA from chemical supply companies, for example - and

are either taking it, or plan to start taking it soon. At least another

50 are actively searching for a supply. One person claims to have got

theirs from chemical giant Sigma-Aldrich based in St Louis, Missouri.

Hogan, the company's chief administrative officer, says it will

not dispatch any chemical to individuals or residential addresses, and

after being alerted to the problem he says Sigma will now tighten up

surveillance on DCA orders. He points out, however, that if a legitimate

company places an order, Sigma has no control over who that company

sells it on to.

In a further twist, thedcasite.com <http://www.thedcasite.com> has a

sister site that sells DCA as a treatment for cancer in animals,

offering a further way for people to get hold of the drug (see " An

online community is born " , below). The FDA says it is investigating the

websites, after being alerted to their existence by New Scientist. Yet

ultimately there may be very little it can do, as DCA is already a

widely used laboratory chemical that can be ordered from thousands of

companies worldwide.

Hogan is clear that his company considers taking DCA to be unsafe. " We

would no more encourage someone to self-medicate with DCA than to drink

poison, " he says. As well as the inherent health risks, there is the

possibility of contamination in laboratory-grade DCA, and not buffering

it correctly could result in severe burns.

" We would no more encourage someone to self-medicate with DCA than to

drink poison "

Burgh has yet to see DCA make any impact on his cancer. Medical scans on

19 March showed that the primary tumour in his thigh has shrunk, and is

less active, but this may be due to the delayed effects of radiotherapy

and chemotherapy Burgh had in January. The number of metastatic tumours

in his lungs has not changed since last month, and they are larger and

more active. " These results are very preliminary, " Burgh stresses, " but

I was really hoping for better results. " On 21 March, he stopped taking

the drug after noticing symptoms which by 24 March included a numbness

in his hands, which he believes to be a sign of neuropathy, and a

hypoglycaemic attack. He advises other people with cancer not to

self-medicate with DCA except under medical supervision. " I am concerned

others may try this drug on their own in desperation, " he says. " DCA is

chemotherapy, a serious drug with potentially serious side effects. "

Michelakis opposes any self-medication with DCA, and the websites that

facilitate it. Though he says he can understand why people with cancer

are motivated to take DCA, he points out that not only are they placing

themselves in danger, they may also be jeopardising the chances of

finding out whether DCA actually works in treating cancer and of it

becoming approved as a therapy. If people become sicker or die while

taking DCA unsupervised, he says, funding and willingness to test it may

disappear. " We are trying to do this the right way, by putting it into

clinical trials, and these websites could destroy all of this. "

From issue 2597 of New Scientist magazine, 28 March 2007, page 8-11

How DCA could affect cancer

The preliminary discovery that DCA may shrink particular cancers in rats

has prompted some to rethink how cancer takes hold in the first place.

One feature of cancer cells is that they produce energy by glycolysis

(the breakdown of glucose) in the cytoplasm, rather than in the

mitochodria, which shut down. Until recently this switch was thought to

be merely a symptom of cancer, rather than anything more fundamental.

Yet DCA seems able to switch the mitochondria back on, and in doing so

it turns on their ability to recognise a cell as abnormal and make it

self-destruct. When Evangelos Michelakis at the University of Alberta

tested DCA on cancer cells in culture, they died. When he gave it to

rats with human tumours, the tumours shrank (Cancer Cell, DOI:

10.1016/j.ccr.2006.10.020).

Earlier findings by two other groups lend support to the mechanism. In

normal cells, DCA has long been known to trigger the switch between

glycolysis and the production of energy in the mitochondria, by

inhibiting an enzyme called pyruvate dehydrogenase kinase (PDK). In

doing so, it decreases lactic acid production, which led to it being

clinically tested, unsuccessfully, as a treatment for lactic acidosis in

children.

In March last year Chi Van Dang at s Hopkins University School of

Medicine in Baltimore, land, showed that inhibiting PDK also

triggers the release of toxic reactive oxygen species by the

mitochondria, resulting in cell death. He speculated that PDK might

therefore be an important therapeutic target for cancer. " My work, in a

sense, confirms Dang's hypothesis, " Michelakis says.

Then in June, Philip Leder at Harvard Medical School in Boston and his

colleagues found that blocking glycolysis in cancer cells through a

different mechanism stimulated their mitochondria and reduced tumour

growth in mice, improving their survival (Cancer Cell, DOI:

10.1016/j.ccr.2006.04.023).

" These papers strengthen the rationale for trying DCA in patients with

cancer, although it doesn't necessarily mean that it will work in humans

in the end, " Michelakis says.

He is submitting protocols to Health Canada for a clinical trial, and

hopes to begin recruiting patients in the coming months. He has also

been contacted by groups in the US, the UK and Canada that are

interested in running human trials of DCA.

An online community is born

Within weeks of the results from animal trials of DCA being published,

two websites were promoting its benefits and facilitating online

discussion about its use.

The first, www.thedcasite.com, claims to act as a gateway for

information on DCA, while the second, www.buydca.com, offers to sell it

for the treatment of cancer in animals. Both sites were founded by Jim

Tassano, who operates a pest-control company in Sonora, California.

While both sites state that DCA has not been approved for human use,

thedcasite.com <http://www.thedcasite.com> has been enthusiastic about

cancer patients giving it a go. " Is DCA worth trying? We absolutely

think so, " the main site read when created in early February this year.

" The risks of a DCA-based therapy are trivial compared to those of

accepted cancer therapy. "

The site also suggested that people donate money to the University of

Alberta, where Evangelos Michelakis and his team continue to test DCA as

a drug, and encouraged people to write to the US Congress and to

doctors, urging them to kick-start clinical trials in cancer patients as

soon as possible.

Michelakis says that since he published his study, and the appearance of

the websites, he has received more than 15,000 emails from people

enquiring about DCA. Around 3000 of them ask about it as a veterinary

drug, with the implication that they are trying to source it for

themselves or another person. He sees a clear link between the pet site

and the questions he is being asked. " At first [people enquiring] were

quite honest, " he says. " But we're now getting emails from people asking

for dosage information for, say, a 150-pound golden retriever. "

Ron Marcinkoski, a pharmacist in Edmonton, Alberta, has also been

contacted by people who he believes have bought DCA from the pet site.

" People are asking me if I can test its purity, if I can encapsulate

it, " he says. " I think it is a major source. "

Tassano maintains that the primary goal of the pet site is to sell DCA

for animal use, although he is aware that people are buying it for

themselves. On 5 March, he posted updates on the health of two people he

claims to have sold DCA to, saying both were doing well. This post has

since been removed. " I can understand why they do it, " he told New

Scientist. " The information is there so they can go to their doctor with

it. Whether they buy their DCA from me is their choice. "

Because DCA has not been approved for human use, it would be illegal for

a website to sell it for human consumption in the US, says special agent

Phil Walsky of the Food and Drug Administration's Office of Criminal

Investigations. His office is investigating the links between the two

sites. Marketing DCA for animal use is also an offence, as it has never

been approved for veterinary use, an FDA spokeswoman says.

Tassano says he is now aware of the FDA's rules, and has amended his

postings over the past few weeks to reflect this. For example, earlier

postings which stated that he had managed to acquire large quantities of

DCA have since been removed, and on 23 February a disclaimer appeared

stating " We do not advocate the use of DCA for human cancer at this

stage and time. "

Tassano maintains he has not made any profit from the sites, and that

they are playing an important role in helping to raise the profile of

DCA. " We are only doing what we think is right. "

No time to lose

" I am just a desperate daughter hoping to find a way to gain a few more

years with my mother, and hoping that my 10-month-old daughter will grow

up knowing her grandmother. " The words of Meg of Ontario, Canada,

reflect the hopes and fears of many families affected by cancer, and

their desire to have access to therapies to treat the condition.

Through a doctor, (a pseudonym) has obtained a supply of DCA for

her mother, who has stage 4 leiomyosarcoma, which has spread to her

lungs. They are waiting on the results of her mother's chemotherapy

before deciding whether to try the chemical, but wish that DCA and other

experimental treatments were more readily available. Clinical trials

take time, and " the public is fed up with waiting on the medical

community to get through their red tape " , she says.

Burgh echoes this view. Because DCA has not been approved as a drug, the

company that supplies pharmaceutical-grade DCA would not sell it to him

without an IND number - a licence occasionally granted by the US Food

and Drug Administration. " I do not have time to wait for an IND number, "

Burgh says. " The process takes about six months - I may be dead by

then. "

One patient group, The Abigail Alliance based in Fredericksburg,

Virginia, is taking the FDA to court to try and force it to open up

access to experimental drugs for terminally ill patients, including

those with cancer. Its founder, Burroughs, says DCA should not be

used in patients until it has undergone safety tests in people with

cancer.

However, he says that in general doctors should be allowed to administer

any drug that has passed initial human safety tests and has shown

promising efficacy. The FDA's existing policies " block the life, liberty

and pursuit of happiness of patients who cannot get into clinical

trials " , the alliance claims. A federal appeals court in Washington DC

ruled in the alliance's favour in May 2006, but is reconsidering its

ruling at the request of the Bush administration. A verdict is expected

within eight months.

The FDA says it is considering regulatory changes that would enable

easier access to experimental medicine, regardless of the outcome of the

court case. Under the proposed rule, expanded access would be available

to individual patients and groups being treated under a systematic plan,

provided that there is no satisfactory alternative therapy for the

disease or condition. A 90-day consultation period ended on 20 March,

but no date has been set for implementing these changes.

Many charities welcome the proposed clarification, saying it will speed

up the decision-making process. Peer-reviewed clinical trials remain the

best way for patients to assess new medicines, says Steve Weiss of the

American Cancer Society. " Yet we recognise that many patients are not

eligible [for clinical trials]. We view this rule as a positive and

necessary step toward balancing the individual needs of patients and

patient safety while also maintaining the integrity of our system of

high-quality, scientifically based and peer-reviewed clinical trials and

patient participation in them. "

The Abigail Alliance says the regulations will merely put into law

current policies which are too stringent. " We believe that the decision

[as to whether to take an experimental drug] should not be the FDA's,

but the patients' in consultation with their doctor, " says Burroughs.