52 replies to this topic

[Futurist1000]

I'm just teasing.

But there needs to be a mechanism for getting cheap compounds to market, if they work. Any Canada gets plenty to market, especially new procedures (that are invented by clinicians and researchers), because we're interested in seeing progress too.

Yeah sorry if I come across as a rabid dog about my opinions. Europe and Canada do bring products to market. I just think they would get even more stuff to market if they didn't have price controls.

[curious_sle]

I am under the impression that if a drug trial didn't cost a billion dollar for the US market prices might not be so high (plenty of drugs fail in the expensive trials) so it is not necessarily the canadian/european price ceiling that hurts innovation but rather the prohibitive costs of bringing a drug to market.

[quicksilver]

Not really comparable.  DCA is a cheap compound that has been around for decades.  It doesn't need to undergo extensive safety tests like most drugs so all they have to do is get enough funding for one clinical trial.  A lot of that funding money is coming from private donations.  You can't compare that to new drugs which need like 800 million to get them approved.  How many new drugs does the canadian government get to market?

There are many great drugs approved in other country sadly will never get approved in the US.

[Futurist1000]

I am under the impression that if a drug trial didn't cost a billion dollar for the US market prices might not be so high (plenty of drugs fail in the expensive trials) so it is not necessarily the canadian/european price ceiling that hurts innovation but rather the prohibitive costs of bringing a drug to market.

Yes, but you have to make enough money when you sell your drug otherwise the company would have a loss. The FDA already makes companies jump through hoops just to get a drug approved. If you have price controls, then the companies can't make enough money to cover the costs of clinical trials. This is the reason we get so many copycat drugs and lifestyle drugs. Companies try to make more money by finding any new disease (resltess legs?) that is helped by an existing drug because it is so difficult to get approval for a new one. Canada and Europe get cheaper drugs, but it is off the backs of the american consumers. Americans have to pay even MORE than they would if there were no price controls in those countries.

There are many great drugs approved in other country sadly will never get approved in the US.

Thats the fault of the FDA, a bloated government bureaucracy that won't approve drugs that already have PROVEN safety records in europe.

[curious_sle]

Mike, don't you contradict yourself a little with these two replies? Americans don't pay more for medication that is approved in Europe but not sold in th US eh?

[Futurist1000]

Mike, don't you contradict yourself a little with these two replies? Americans don't pay more for medication that is approved in Europe but not sold in th US eh?

If my sentence was confusing or not clear, I'm sorry. What I meant to say is that there are drugs in Europe that we don't get because they are off patent in Europe and the European companies would have to undergo expensive clinical trials AGAIN in the U.S.. The FDA doesn't seem to care that a drug has been proven to work in another market. There are many drugs that have an extensive safety record in Europe, but they will NEVER get to the U.S. market because companies in Europe won't make enough money on them to recoup their losses so they don't even bother. The FDA often wants a european company to perform MORE clinical trials in order to get a drugs approval in the States. If your drug is already off patent, then there is no incentive to pay for those clinical trials since no money can be made. I hope that clarifies my position somewhat. I would place blame on the FDA, but many people think they are just protecting the american drug consumer.

[niner]

I would place blame on the FDA, but many people think they are just protecting the american drug consumer.

Ever hear of thalidomide?

[Futurist1000]

Ever hear of thalidomide?

That was years ago before did teratogenicity tests on drugs. To me, if a drug has a safety record in Europe, I don't see any reason why it shouldn't be allowed to be marketed here. There are a lot of drugs that will just never get approved here merely because they are off patent and the makers of the drugs won't be able to recoup their losses. (you can buy them online though). I'm not saying to abolish the FDA or anything. There is a balance between side effects of a drug and lives saved.

You might want to read this wikipedia article on criticism of FDA.
Criticism_of_the_FDA

The economist Milton Friedman has claimed that the regulatory process is inherently biased against approval of some worthy drugs, because the adverse effects of wrongfully banning a useful drug are undetectable, while the consequences of mistakenly approving a harmful drug are highly publicised and that therefore the FDA will take the action that will will result in the least public condemnation of the FDA regardless of the health consequences.[2]

Friedman has also argued that delays in the approval process have cost lives.[3] Prior to passage of the Kefauver Harris Amendment in 1962, the average time from the filing of an investigational new drug application (IND) to approval was 7 months. By 1998, it took an average of 7.3 years from the date of filing to approval.[4] Prior to the 1990s, the mean time for new drug approvals was shorter in Europe than in the United States, although that difference has since disappeared.[5]

I think we should debate the pros and cons of EVERY government agency. There are always consequences to specific laws. Many times these consequences are not readily visible, but they DO have a measurable affect. I think I tend to be fairly skeptical of government. We can't just give it a blank check and expect everything to work out OK.

[neogenic]

Well, I was doing some sports nutrition research and came across a number of studies using DCA via infusion (later found some oral) reducing lactic acidosis and increasing mitochondrial function. Then I stumbled in to a number of sites stating it is a cure for Cancer. While I'd be reluctant to believe the last part, I posted an article below. Regardless, its effects are fascinating if only for ischemia, athletes, etc. I am suprised I didn't know about this and there are many studies on it. I'd love to hear thoughts on this. A side effect is polyneuropathy with consistent use, so people use thiamine, fursultiamine, allithiamine, sublutiamine, benfotiamine, etc.

http://www.newscient...for-cancer.html
Wednesday, January 17, 2007
A cheap and simple cure for cancer?
New Scientist has received an unprecedented amount of interest in this story from readers. If you would like up-to-date information on any plans for clinical trials of DCA in patients with cancer, or would like to donate towards a fund for such trials, please visit the site set up by the University of Alberta and the Alberta Cancer Board. We will also follow events closely and will report any progress as it happens.

It is rare to find a drug that sweeps away decades of assumptions and reveals a radical approach to treating all forms of a disease. But a simple, small molecule called dichloroacetate (DCA) has done just that - and to that most dreaded of diseases: cancer.

The new findings, might also force a rethink on what actually causes cells to turn cancerous in the first place.

In 1930, biochemist Otto Warburg, proposed that cells turn cancerous through a fundamental change in the way they generate their energy. Normally, cells use specialised organelles called mitochondria to supply their energy. Cancer cells shift to a process called glycolysis which takes place in the main body of the cell. Glycolysis is an inefficient system of making energy which normal cells employ only when oxygen is in short supply, switching to mitochondrial energy production when oxygen levels increase.

Curiously, Warburg discovered that cancer cells continue to use glycolysis even when oxygen is plentiful. He called this the ???Warburg effect???, and claimed it was common to all cancer cells.

His ideas were dismissed and buried long ago, not least when another famous biochemist, Hans Krebs, said the Warburg effect was a symptom of cancer, not the primary cause. This scepticism was reinforced by the belief that cancer cells switch to glycolysis because their mitochondria are damaged and don???t work any more.

Enter DCA, which has been used for years to treat people with mitochondrial disease. The drug boosts the ability of mitochondria to generate energy. When given to cancer cells it did the same: the cells switched from glycolysis to mitochondrial energy production. What's more, functional mitochondria help cells recognise functional abnormalities and trigger cell death.

In tests, the DCA caused cancer cells to lose their ???immortality??? and die. When the drug was given to rats with human tumours, the tumours shrank. Warburg may have been right after all - glycolysis may be more than just a symptom of cancer.

So why not rush straight into clinical trials with this drug? It is cheap, does not appear to affect normal cells, we know its side effects, and it should work on all cancers.

There's a hitch: dichloroacetate is an old drug and so cannot be patented. The upshot is that pharmaceutical companies can???t stop rivals making and selling it more cheaply, so it???s not worth their while to go to the huge expense of testing it in clinical trials.

This is not a new problem. Many drugs are left on the shelf because companies cannot make lots of money from them. It has happened for diseases that affect mainly poor people, such as TB, although there are now an increasing number of initiatives to help deal with these cases. But cancer is historically a disease that chiefly afflicts the rich, and testing DCA will need a one-off effort.

Drugs companies will be falling over themselves to find a patentable drug with similar action to DCA. Any of these that reach the market will be hugely expensive. It would be a scandal if a cheap alternative with such astonishing potential were not given a chance simply because it won't turn a big enough profit.

Andy Coghlan, senior reporter

[nameless]

If this is true, I wonder how other therapies that deal with cell mitochondria would affect cancer. CoQ10/Ubiquinol comes to mind... and I do recall a small study on breast cancer from years ago that showed it did shrink some tumors.

[neogenic]

If this is true, I wonder how other therapies that deal with cell mitochondria would affect cancer. CoQ10/Ubiquinol comes to mind... and I do recall a small study on breast cancer from years ago that showed it did shrink some tumors.

I don't know, but its application has been a number of disease sets like with COPD. It used to be used for performance with race dogs when combined with DMG...something like pangamic acid it said, but has been tied to toxicity in a number of tissues. I don't know if that is linear or a threshhold (e.g. antioxidant vs. pro-oxidant)...

Am J Respir Crit Care Med. 2008 Feb 8 [Epub ahead of print] Links
Dichloroacetate Enhances Performance and Reduces Blood Lactate during Maximal Cycle Exercise in COPD.Calvert LD, Shelley R, Singh SJ, Greenhaff PL, Bankart J, Morgan MD, Steiner MC.
Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Institute for Lung Health, Leicester, Leicestershire, United Kingdom.

RATIONALE: Impaired skeletal muscle function contributes to exercise limitation in patients with chronic obstructive pulmonary disease (COPD). This is characterised by reduced mitochondrial adenosine triphosphate (ATP) generation, and greater reliance on non-mitochondrial energy production. Dichloroacetate (DCA) infusion activates muscle pyruvate dehydrogenase complex (PDC) at rest, reducing inertia in mitochondrial energy delivery at the onset of exercise and diminishing anaerobic energy production. OBJECTIVES: This study aimed to determine whether DCA infusion enhanced mitochondrial energy delivery during symptom-limited maximal exercise, thereby reducing exercise-induced lactate and ammonia accumulation and, consequently, improving exercise performance in COPD patients. METHODS AND MEASUREMENTS: A randomised, double-blind crossover design was used. Eighteen COPD subjects performed maximal cycle exercise after an intravenous infusion of DCA (50mg/kg body mass) or saline (control). Exercise work output was determined, and blood lactate and ammonia concentrations were measured at rest, 1 and 2 minutes of exercise, peak exercise, and 2 minutes post-exercise. MAIN RESULTS: DCA infusion reduced peak blood lactate concentration by 20% [mean(SE) difference 0.48(0.11)mmol/l, p<0.001] and peak blood ammonia concentration by 15% [mean(SE) difference 14.2(2.9)umol/l, p<0.001] compared with control. Following DCA, peak exercise workload improved significantly by a mean(SE) of 8(1)watts [p<0.001] and peak oxygen consumption by 1.2(0.5)ml/kg/min [p=0.03] compared with control. CONCLUSION: We have shown that a pharmacological intervention known to activate muscle PDC can reduce blood lactate and ammonia accumulation during exercise and improve maximal exercise performance in COPD subjects. Skeletal muscle PDC activation may be a target for pharmacological intervention in the management of exercise intolerance in COPD.

[lynx]

Dichloroacetate causes toxic neuropathy, but 25 mg/kg seems high.

Neurology. 2006 Feb 14;66(3):324-30. Links

Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial.Kaufmann P, Engelstad K, Wei Y, Jhung S, Sano MC, Shungu DC, Millar WS, Hong X, Gooch CL, Mao X, Pascual JM, Hirano M, Stacpoole PW, DiMauro S, De Vivo DC.
Department of Neurology, Columbia University, New York 10032, USA. pk88@columbia.edu

OBJECTIVE: To evaluate the efficacy of dichloroacetate (DCA) in the treatment of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). BACKGROUND: High levels of ventricular lactate, the brain spectroscopic signature of MELAS, correlate with more severe neurologic impairment. The authors hypothesized that chronic cerebral lactic acidosis exacerbates neuronal injury in MELAS and therefore, investigated DCA, a potent lactate-lowering agent, as potential treatment for MELAS. METHODS: The authors conducted a double-blind, placebo-controlled, randomized, 3-year cross-over trial of DCA (25 mg/kg/day) in 30 patients (aged 10 to 60 years) with MELAS and the A3243G mutation. Primary outcome measure was a Global Assessment of Treatment Efficacy (GATE) score based on a health-related event inventory, and on neurologic, neuropsychological, and daily living functioning. Biologic outcome measures included venous, CSF, and 1H MRSI-estimated brain lactate. Blood tests and nerve conduction studies were performed to monitor safety. RESULTS: During the initial 24-month treatment period, 15 of 15 patients randomized to DCA were taken off study medication, compared to 4 of 15 patients randomized to placebo. Study medication was discontinued in 17 of 19 patients because of onset or worsening of peripheral neuropathy. The clinical trial was terminated early because of peripheral nerve toxicity. The mean GATE score was not significantly different between treatment arms. CONCLUSION: DCA at 25 mg/kg/day is associated with peripheral nerve toxicity resulting in a high rate of medication discontinuation and early study termination. Under these experimental conditions, the authors were unable to detect any beneficial effect. The findings show that DCA-associated neuropathy overshadows the assessment of any potential benefit in MELAS.

PMID: 16476929 [PubMed - indexed for MEDLINE]

[neogenic]

Yes, some have stated this on Cancer board and hence the multiple thiamin uses. Still it'd be interesting to delve in to the science as people are making fairly incredible claims with it much like IV Vitamin C.

[niner]

Well, I was doing some sports nutrition research and came across a number of studies using DCA via infusion (later found some oral) reducing lactic acidosis and increasing mitochondrial function. Then I stumbled in to a number of sites stating it is a cure for Cancer. While I'd be reluctant to believe the last part, I posted an article below. Regardless, its effects are fascinating if only for ischemia, athletes, etc. I am suprised I didn't know about this and there are many studies on it. I'd love to hear thoughts on this. A side effect is polyneuropathy with consistent use, so people use thiamine, fursultiamine, allithiamine, sublutiamine, benfotiamine, etc.

I didn't know about the sports angle on DCA. (Maybe Roger Clemons should have gone this route instead) I agree with you as far as the cancer part goes- see below.

http://www.newscient...for-cancer.html
Wednesday, January 17, 2007
A cheap and simple cure for cancer?
[...]
There's a hitch: dichloroacetate is an old drug and so cannot be patented. The upshot is that pharmaceutical companies can't stop rivals making and selling it more cheaply, so it's not worth their while to go to the huge expense of testing it in clinical trials.

This is not a new problem. Many drugs are left on the shelf because companies cannot make lots of money from them. It has happened for diseases that affect mainly poor people, such as TB, although there are now an increasing number of initiatives to help deal with these cases. But cancer is historically a disease that chiefly afflicts the rich, and testing DCA will need a one-off effort.

Drugs companies will be falling over themselves to find a patentable drug with similar action to DCA. Any of these that reach the market will be hugely expensive. It would be a scandal if a cheap alternative with such astonishing potential were not given a chance simply because it won't turn a big enough profit.

Andy Coghlan, senior reporter

Another 100mpg carburetor, eh? I think this is a somewhat ridiculous paranoid idea. We do have the NIH, and Universities, and Non Profit Institutes. If there was really something to this, people would be falling all over themselves to be "the person who cured cancer", get the Nobel Prize, hundreds of honorary degrees, get to have sex with starlets... or at least hang around with famous people. You don't have to be a money grubbing drug company to demonstrate that a drug works well in animals, for example. If you could demonstrate that it had a decent chance of working, I'm sure you could pry enough money for a clinical trial out of the Gates Foundation.

[stephen_b]

The University of Alberta DCA site is here. You can make a donation for the upcoming clinical trial that they are running. They need donations, since DCA is not patentable, and no drug company is going to touch it.

Their study that sparked all of the interest, by the way, was in vitro on rat cell lines.

Stephen

[niner]

The University of Alberta DCA site is here. You can make a donation for the upcoming clinical trial that they are running. They need donations, since DCA is not patentable, and no drug company is going to touch it.

Their study that sparked all of the interest, by the way, was in vitro on rat cell lines.

Any in vivo studies?

[inawe]

Contrary to what this guy, Andy Coghlan (senior reporter?) wrote in
his piece (of ....), research on DCA was and is being done by several groups.
What this shows is that it's much easier for a reporter to write a
sensationalist article in a few minutes, than to do serious research.
A lot of research was done by the Stacpoole group at the University of
Florida (PMID: 18096758 and other papers). As mentioned by other
posters, there is the danger of peripheral neuropathy.
See also http://cla-dca.gcrc....familyinfo.html.

[neogenic]

Contrary to what this guy, Andy Coghlan (senior reporter?) wrote in
his piece (of ....), research on DCA was and is being done by several groups.
What this shows is that it's much easier for a reporter to write a
sensationalist article in a few minutes, than to do serious research.
A lot of research was done by the Stacpoole group at the University of
Florida (PMID: 18096758 and other papers). As mentioned by other
posters, there is the danger of peripheral neuropathy.
See also http://cla-dca.gcrc....familyinfo.html.

In nearly every post I have on here I've discussed that aspect. Still I'd like to discuss the merit and mechanisms of potential benefits. I have no plans on taking it. I just think it very interesting and worth kicking around with the collective brain that is imminst.org

[rhodan]

First update on DCA I have seen in months :

http://news.bbc.co.u...lth/7292652.stm

The article says that some tests are done on DCA but no reference.

[sUper GeNius]

Well, I was doing some sports nutrition research and came across a number of studies using DCA via infusion (later found some oral) reducing lactic acidosis and increasing mitochondrial function. Then I stumbled in to a number of sites stating it is a cure for Cancer. While I'd be reluctant to believe the last part, I posted an article below. Regardless, its effects are fascinating if only for ischemia, athletes, etc. I am suprised I didn't know about this and there are many studies on it. I'd love to hear thoughts on this. A side effect is polyneuropathy with consistent use, so people use thiamine, fursultiamine, allithiamine, sublutiamine, benfotiamine, etc.

I didn't know about the sports angle on DCA. (Maybe Roger Clemons should have gone this route instead) I agree with you as far as the cancer part goes- see below.

http://www.newscient...for-cancer.html
Wednesday, January 17, 2007
A cheap and simple cure for cancer?
[...]
There's a hitch: dichloroacetate is an old drug and so cannot be patented. The upshot is that pharmaceutical companies can't stop rivals making and selling it more cheaply, so it's not worth their while to go to the huge expense of testing it in clinical trials.

This is not a new problem. Many drugs are left on the shelf because companies cannot make lots of money from them. It has happened for diseases that affect mainly poor people, such as TB, although there are now an increasing number of initiatives to help deal with these cases. But cancer is historically a disease that chiefly afflicts the rich, and testing DCA will need a one-off effort.

Drugs companies will be falling over themselves to find a patentable drug with similar action to DCA. Any of these that reach the market will be hugely expensive. It would be a scandal if a cheap alternative with such astonishing potential were not given a chance simply because it won't turn a big enough profit.

Andy Coghlan, senior reporter

Another 100mpg carburetor, eh? I think this is a somewhat ridiculous paranoid idea. We do have the NIH, and Universities, and Non Profit Institutes. If there was really something to this, people would be falling all over themselves to be "the person who cured cancer", get the Nobel Prize, hundreds of honorary degrees, get to have sex with starlets... or at least hang around with famous people. You don't have to be a money grubbing drug company to demonstrate that a drug works well in animals, for example. If you could demonstrate that it had a decent chance of working, I'm sure you could pry enough money for a clinical trial out of the Gates Foundation.

[chomping on my morning Laetrile]
I wholeheartedly disagree!

[neogenic]

From the Methyl Jasmonate thread r/t Grouppe Kurosawa's Cancer protocol I found this:

9. DCA, 12mgs/kilo of body weight every OTHER day. Take it as one dose in the morning. Dissolve in juice or water. DCA should NOT be used to treat brain cancer.
http://grouppekurosa...vailabilit.html
http://grouppekurosa...ine-enhanc.html
DCA is largely unavailable to US citizens because the FDA has banned its use.
http://www.buydca.com/

10. Caffeine. See essay above. Caffeine enhances the efficacy of DCA. Consume as much as you can stand.
Caffeine is also an mTOR inhibitor. The combination of mTOR and glycolysis inhibitors powerfully promotes programmed cell death. MTOR is the natural inhibitor of autophagy.


I thought it was interesting, given this thread I had brought up a while back and the ingredients controversial nature.

[Mind]

I saw an old story about DCA dredged up in Twine today. Any news about the Canadian trial? Anybody hear of any anecdotal success stories? I know a lot of people tried it on their own.

[Mind]

I didn't know this site existed: The DCA Site.

This is the only recent study I found about its use as a cancer treatment. http://www.medicorca...m/dca-data.html Far from a silver bullet, but perhaps could be beneficial when used in conjunction with other treatments.