[Perryc]

The FDA issued the following announcement this afternoon. While removal of a drug from the market, especially after 20 years, is unusual, in this case the evidence supports this action. Many doctors have already been getting their patients off the drug, which has been associated with dangerous heart valve problems in recently published studies. Much to its credit, The FDA credit has sought the advice of patients in making this decision and in communications with the PD community.

Perry Cohen
Parkinson Pipeline Project
FDA Patient Representative


Dear Colleague:

The U.S. Food and Drug Administration (FDA) today announced that manufacturers of pergolide drug products, which are used to treat Parkinson’s disease, will voluntarily remove these drugs from the market because of the risk of serious damage to patients’ heart valves. FDA has issued a Public Health Advisory detailing the removal of pergolide products from the market.

The products being withdrawn are Permax, the trade name for pergolide marketed by Valeant Pharmaceuticals, and two generic versions of pergolide manufactured Par and Teva. Pergolide is in a class of medications called dopamine agonists and is used with levodopa and carbidopa to manage the symptoms (tremors and slowness of movement) of Parkinson's disease.

In 2006, an estimated 12,000 patients received prescriptions for pergolide from retail pharmacies in the United States. Patients taking pergolide should contact their doctors to discuss alternate treatments. Patients should not stop taking the medication, as stopping pergolide abruptly can be dangerous.

There are alternative therapies available for Parkinson’s disease, including three other dopamine agonists that have not been associated with valvular heart disease. The removal of pergolide products is not expected to adversely affect patient care because of the alternative therapies available.

For additional information, the press release and links to the Public Health are available at http://www.fda.gov/bbs/topics/NEWS/2007/NEW01596.html.

FDA held a press conference today consisting of a short presentation by FDA officials followed by a question and answer session. The replay can be heard today after 4:00 pm EST by calling 1-800-944-3584, and it will be available for listening through April 2, 2007.

If you need additional information, please contact David Banks or Brenda Evelyn at 301-827-4460.

Sincerely,

David Banks, RPh., PhD.
Office of Special Health Issues
U.S. Food and Drug Administration
5600 Fishers Lane, Room 9-49
Rockville, Maryland 20857
David.Banks@fda.hhs.gov

[Thelma]

Cancer therapy: When all else fails
28 March 2007
Exclusive from New Scientist Print Edition. Subscribe and get 4 free issues.
Linda Geddes

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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 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 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. Michael 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 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 Johns Hopkins University School of Medicine in Baltimore, Maryland, 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 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 Walker 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, Walker (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, Frank 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.

[steffi 001]

Well hey ho...I`ll just go take a swig of petrol from the tanker in the car...and maybe a slurp of Jeyes fluid. With a dash of paint thinner of course.

And while I`m cleaning out the sink i`ll steal a swig of bleach !!!


MY GOSH. Are folk really doing this? Well NOT my cocktail of course..but the science lab liquid jobby?
Makes battery fluid seem a possibility.
I don`t know if it`s brave or stupid,desparate or "life from another planet"
intelligence. My chin is still on the floor.
Ooooh. Please keep us posted on this one.I am fascinated.But...what does their breath smell like...and can they still smoke? Go near a bonfire,barbeque...what?
Does it come with a warning other than "We aint tested this fully...yet...but we`ll have fun watching each other grow furry ears"

Just going to remove my nail polish....mmmm now that smells good enough to...drink...

This site should get an award for bringing the most surreal,amazing,innovative stories to light.

[steffi 001]

Truly I hope my last post hasn`t iupset anyone. I do so realise and appreciate the seriousness of the disease.
So my sincere apologies if anyone feels my "take" on the story is inappropriate.
I would never seek to hurt anyones feelings.
I am just completely amazed by this news and my brain is doomed to see the humour in most things.

Anyhow...once again...my very humble apologies

Steffi

[reverett123]

But first, the action on the mitochondria could mean very big news for PD since that seems to be a key feature. Too bad most of us will be dead before we know.

As to philosophies- Some feel that our bodies belong to us and that we are entitled to do anything we darned well want to with it so long as we don't hurt anyone else.

Some of us feel that if it has not been approved by the authorities that we shouldn't.

But there is also a group who do not have an illness but who feel that we shouldn't take anything until THEY say we can. Even if we are dying of cancer and they have nothing to offer us. They say we should die quietly because they say we should. That really is what they are saying. Who gave them that power?

Ah, power. Here's a prediction- Watch for further calls to curtail these uppity patients by restricting access to Medline. Control of information is as old as "The Prince". Heck, as old as humanity.

[Perryc]

Our motto at the Pipeline Project....is

"The missing ingredient in development of new therapies is the voice of the patient"

We have been working with FDA as the first Neurological disease to participate in their "Patient Consultants" programs to have well qualified patient advocates at the table or telephone most often when companies seek approval to enter a new phase of development and when they present findings of studies to regulators. Alzheimer's will soon join our program.

We have also worked with a half dozen companies in the past to bring our unique experience to them in their design and planning for clinical trials. This component will be expanding in the near future, so keep a lookout for an announcement to recruit volunteers as Industry PD Consultants.

Other tasks need to be done as well such as tracking developments for our data base of new therapies in the pipeline, and developing and presenting training programs for PD audiences on the importance of the pipeline and what they can do to remove barriers to introduction of safe and effective new treatments for PD. see www.pdpipeline.org for mor information.

Perry

[ZucchiniFlower]

I buy from Sigma for my lab, so I looked up Sodium dichloroacetate (Dichloroacetic acid sodium salt), and 10 g cost $28.70, so it's cheap. I've had breast cancer, but can't imagine taking something like this. "First do no harm" seems to apply here. I can see how online groups can encourage people to jump off a cliff...and maybe I could be persuaded, too, if death were really looming. It's an interesting lead.

I don't get why pergolide was on the market for so long since there are safer alternatives. I hope most neuros were paying attention to the dangers and stopped prescribing it some time ago.

[Floridagal]

Hello! as far as I'm concerned, I think if it's my body then I get to choose what might help me, as long as I am aware of what my risks are. There are plenty of main line approved medications that have harmed many, many people. I think it's more about loss of control by the medical community and pharmaceutical companies than anything else. People without much hope of survival shouldn't be judged by anyone if they want to try something that might be harmful, cause like I said, look how many "safe" drugs, turn out to not be so safe, That's my opinion anyway. Floridagal

[lou_lou]

"Nerve Cells Differ Most at the Molecular Level"
(This is from an email from my sister who lives in France sent me) .

Dear Tena,

An anatomist with a PhD, whom I knew said to me while I was taking a class on autopsy findings - said that of the nearly one thousand bodies he had studied , (and he is the head of the anatomy department,) he said that there were some who should not have been able to be alive, yet apparently had functioned normally, but they were alive and should not have been.

There is a book called “Principles of Neural Science By Eric R. Kandel, James Haris (1932-) Schwartz, Thomas M. Jessell” - if you wish to study.

(Paraphrased) There are some neurons that do not fit the model of neuron signaling; which either have no axons, or such a short one that a conducted signal is not required. There are also neurons that lack a steady resting potential and are spontaneously active.
Quoted:
"... different ion channels provide neurons (and other cells too Tena) with various thresholds, excitability properties, and firing patterns. Thus neurons with different ion channels can encode the same class of synaptic potential into different firing patterns and thereby convey different signals."

(Tena, how are your potassium/sodium levels?)
See: hypoadrenia, positive paradoxical pupillary reflex, low mineralocorticoid levels. Some of your nervousness could be related to adrenals.)

"Neurons also differ in the chemical transmitters they use to transmit information to other neurons, and in the receptors they have to receive other information from other neurons...... a disease may effect only one class of neurons but not others......
Parkinson's disease, a disorder of voluntary movement, damages a small population of interneurons that use dopamine as a chemical transmitter. Some diseases are selective even within the neuron, affecting only the receptive elements, the cell body, or the axon.......
Despite the differences among nerve cells, the basic mechanisms of electrical signaling are surprisingly similar. This simplicity is fortunate for those who study the brain. By understanding the molecular mechanisms that produce signaling in one kind of nerve cell, we are well on our way to understanding these mechanisms in many other nerve cells."

I believe God is called "The Creator" because He is Creative !!!
Love,
Mimi

[made it up]

Thankyou Perry for posting the article regarding Permax.
I'm glad it's been taken off the market.
Anyone who's taken it in the past should get an echocardiogram to check their heart.
Am unsure about whether or not valvulopathy can occur sometime after ceasing permax, must ask neurologist that.
Cheers,
Lee