Dichloroacetate - Miracle brain cancer drug or overhyped disappointment?
I've realized that blogging about topical drug or poison news is kinda fun, so here's another actual blog post. CBC News has reported that Health Canada (the Canadian FDA) just approved a phase 2 clinical trial (testing a drug in a small number of sick people to see if it helps them get better) to see if a compound called dichloroacetate (dichloroacetic acid, DCA) can help people with glioblastoma multiforme, an incurable variety of brain cancer that typically knocks people off within a year of diagnosis.
DCA is a relatively simple chemical; It's essentially just vinegar (acetic acid) with a couple of chlorine atoms taking the place of hydrogen atoms. It is currently a generic (off patent) drug used to treat lactic acidosis, a potentially serious condition associated with a number of things including certain inherited mitochondrial diseases (e.g. MELAS), hypoglycemia (low blood sugar, a recurring issue with diabetes mellitus), severe malaria, and anything that results in a prolonged period of reduced systemic oxygen availability (shock, ischemic heart disease, anemia, etc.). By indirectly up-regulating the pyruvate dehydrogenase complex (PCD), a group of three enzymes that convert pyruvate (pyruvic acid) into acetyl-CoA, in the mitochondria of cells, DCA reduces the amount of pyruvate that would otherwise be converted into lactate (lactic acid) in the cytoplasm. As lactate is a fermentation product, it can accumulate in the body under anaerobic (no oxygen) conditions and produce a variety of metabolic acidosis.
By boosting aerobic (oxygen-dependent) cellular respiration, DCA reportedly attenuates the oxygen-independent pathway of energy production preferred by cancer cells, causing tumors to shrink. The compound has been shown to shrink tumors in rats and kill human cells in vitro (in laboratory cell cultures).
The CBC article states that DCA does not affect normal cells, such that its side effects, if any, would be considerably less terrible than those for 'typical' anticancer drugs (e.g. nausea and fatigue). Given that DCA has been used to treat lactic acidosis for a while now without any particularly serious adverse effects showing up, this is probably true. Interestingly, DCA is a confirmed animal carcinogen, having been shown to increase the incidence of liver cancers in mice. There is insufficient human data to say whether or not it can cause cancer in people. DCA has also been found to have neurotoxic effects in lab animals, but reports of such effects in humans are sparse and controversial.
In any event, the Wikipedia article on DCA makes a good point, which is that the overwhelming majority of new drugs never make it to a pharmacy's shelves. DCA is neat because scientists, small Albertan towns, and private citizens, not big pharmaceutical companies, are paying for its development, but ultimately the chances of it becoming the miracle drug the media is making it out to be are depressingly slim.
If you are addicted to opiate painkillers like Percocet, drug treatment options are available that have been shown to be effective. One variety of drug rehab involves suboxone treatment, where a drug is given to help you detoxify.
- Stacpoole PW, Nagaraja NV, Hutson AD. Efficacy of dichloroacetate as a lactate-lowering drug. J Clin Pharmacol. 2003 Jul;43(7):683-91. Review.
- http://www.depmed.ualberta.ca/dca/
- Hazardous Substances Data Bank (HSDB) record for Dichloroacetic Acid [no permanent link available]
3 chemically inspired comments:
A terribly spry and healthful GBM patient here, one of the ones that hasn't yet been knocked off in a year.
I belong to a couple DCA forums, and am happy to know a couple folks that are on DCA and exhibiting tumor shrinkage. So far so good.
Score one for blatant insensitivity on my part! I'm glad to hear that GBM isn't getting you down. Fingers crossed for DCA making it as a drug.
You and, charitably, almost everyone else is really missing the point. The real news is that it is possible to reactivate mDNA in cancer cells. It leads us down a whole new line of research that may eventually far exceed the benefits of just DCA.
Post a Comment