October 2016 Hero of the Month:
Dr. Paul Alan Cox
Paul Alan Cox, Ph.D., is one of the world's top ethnobotanists, a scientist who specializes in the search for pharmacologically active plants used by indigenous peoples to treat, cure, or even prevent illness. He founded and directs the U.S.- based Institute for Ethnomedicine, a nonprofit dedicated to identifying new medicines from plants used by indigenous peoples. Cox, a devout Mormon who speaks more than a dozen languages, is one of the leading voices pushing for biological conservation to ensure that plants and animals that may offer new ways to treat diseases do not vanish, unrecognized, from the earth.
Although he has won prestigious scientific awards all over the globe, until now Cox has perhaps best been known as the author of the book Nafanua, detailing his successful efforts to save thousands of acres of the Samoan rainforest from logging. Cox raised the necessary funds by founding a cosmetics company that uses extracts from native Samoan plants, and by identifying another Samoan plant now being developed as a treatment for AIDS. Among his many other accomplishments, Cox is also well-known for creating the 50th U.S. National Park, The National Park of American Samoa.
Now Cox has turned his attention to one of the most vexing problems in medicine: how to prevent so-called "protein tangle" neurodegenerative diseases. All of these diseases - which include Alzheimer's, Parkinson's, ALS, Lewy body dementia, Pick's disease, and supranuclear palsy - are characterized by "misfolding" proteins in the nerve cells: the proteins tau and amyloid for Alzheimer's, and other proteins for each of the other neuronal diseases.
Cox has come to believe that the misfolded proteins are not the cause of the diseases, but the result of exposure to a natural but highly toxic environmental protein, BMAA (beta-N-methylamino-L-alanine). And, true to form, he has also identified another protein, L-serine, that may confer a resistance, or even an outright immunity, to the neurotoxic effects of BMAA.
Paul Alan Cox and his team at the Institute for Ethnomedicine in Jackson, Wyoming. Photo from p. 60 of Sept. 2016 Southwest, The Magazine
Cox's insight arose from his familiarity with Guam and its flying foxes – giant fruit bats which Cox had previously identified as important pollinators of rain forests. Cox learned that nearly a quarter of Guam's Chamorro population had been affected by a serious neurodegenerative protein tangle disease called "Lytico-bodig," or "listless paralysis," which bore all the hallmarks of several other "protein tangle" diseases: Alzheimer’s, Parkinson’s, and ALS. Although neurologists had tried and failed for five decades to identify the cause of Lytico-bodig, it occurred to Cox that the flying foxes might play some role. When Cox and his two of his scientific colleagues flew to Guam and interviewed the Chamorros, they found that, indeed, the flying foxes were a favorite food of the Chamorros. Yet the native peoples on other islands nearby ate flying foxes without any ill effects.
Cox learned that during World War II the Chamorros had discovered that Guam's flying foxes were easy to catch when startled by gunfire. After that, the Chamorros caught and consumed so many that flying foxes became nearly extinct on the island. The Chamorros then began importing them from other islands, but were disappointed to find that the imports were not as tasty as the native flying foxes. And about a decade after the native flying foxes declined, the rate of Lytico-bodig among the Chamorros began to fall.
Cox found that on Guam, the flying foxes ate large quantities of cycad seeds, which contain high quantities of the neurotoxin BMAA, produced by cyanobacteria within the plants’ roots. On the other islands -- the ones with the less-tasty flying foxes and no Lytico-bodig disease -- the BMAA-containing seeds were not part of the flying foxes' diet.
In collaboration with Australian researchers, Cox found that BMAA displaces the amino acid L-serine, which is essential to the development and maintenance of the human nervous system. Unfortunately, the cyanobacteria that produce BMAA are nearly ubiquitous in nature: they exist in deserts, the antarctic, oceans, lakes - and on moist surfaces in human devices such as air-conditioner filters and car radiators. People eat, breathe, and even bathe in these highly toxic bacteria every day.
But Cox also knew that there was one population who seemed immune to any neurodegenerative “protein tangle” diseases: the villagers of Ogimi on Okinawa island in Japan. Ogimi has the highest population of centenarians - healthy, active centenarians at that - in the world. Although they had the same exposure to BMAA as anyone else, the Ogimi villagers consumed extremely high quantities of L-serine in the chief components of their diet, tofu and seaweed. Putting all of these facts together, Cox concluded that BMAA was a potential cause of most or even all neurodegenerative diseases, and that high L-serine consumption might somehow prevent BMAA from displacing L-serine in the human nervous system and thereby wreaking havoc on the brain and spinal cord. Because it appears that certain families are genetically susceptible to "protein tangle" diseases such as ALS and Alzheimer's, Cox is hopeful that L-serine may prove to be a broadly applicable preventative measure for these families as well as those without any genetically-related neurodegenerative diseases.
Now Cox has successfully tested his theory on vervets, small African monkeys whose nervous system bears many resemblances to that of humans. Cox and his researchers have found that vervets fed fruit containing significant amounts of BMAA show the formation of “Alzheimer’s-like” brain tangles and amyloid deposits like the ones seen in the Chamorros islanders affected by Lytico-bodig disease, as well as microglial action in the spinal cord like that seen in ALS. And his research has also found that vervets fed equal amounts of L-serine and BMAA have a “stunningly” reduced density of protein tangles. Cox believes that his work with vervets points the way to an animal model on which researchers can test any new Alzheimer's drug discovery, something currently lacking in a field where drug safety and efficacy tests now require years and even decades of human trials.
As far as L-serine goes, Cox believes that it somehow sends up an "alert" to the nervous system, meaning L-serine serves as something akin to a vaccine against BMAA. A clinical trial sponsored by Cox' Institute for Ethnomedicine has found that patients can safely tolerate up to 30 grams of L-serine per day. More clinical trials to test if L-serine is an effective treatment for ALS are now underway.
One of the drawbacks to extensive clinical testing of L-serine may be that L-serine is not a patentable substance - a bottle of sixty 500 mg. (i.e., half of one gram) tablets of L-serine, produced in a USA-based, FDA-registered laboratory, is classified by the FDA as a food substance and can be purchased on Amazon.com for less than $30.00. That means there is no potential "gold mine" for any drug company that might otherwise underwrite its testing. But Cox's team of scientists are so convinced of L-serine's efficacy in preventing neurodegenerative diseases that, as one team member recently noted, "we are all taking it."
Dr. Paul Alan Cox's TED talk on the topic of BMAA and L-serine, and L-serine's potential in treating ALS, can be viewed on You Tube. For his selfless efforts in this research, and his innumerable other medical discoveries and accomplishments (see Brainchemistrylabs.org/paul-alan-cox/), Dr. Cox unquestionably deserves Time magazine's label as a "Hero of Modern Medicine," and our gratitude as well. -- Jim