Regional Archives — The Altamont Enterprise, March 1, 2012
Extraterrestrial amino acid
A seizure cure in a meteor?
ALBANY — When the Murchison meteorite fell in rural Australia in 1969, it delivered a rich cache of chemical compounds, and recent research by a scientist at Albany Medical Center has shown that one of these extraterrestrial materials may have anti-convulsive characteristics that could help prevent or reduce seizures in people with epilepsy.
“But it’s very early on in the research we are doing,” Dr. Damian Shin told The Enterprise. “I don’t want people to think this will cure epilepsy in the immediate future. Epilepsy neurologists use a battery of drugs, because epilepsy itself is kind of a spectrum of disorders. It’s a tough condition to treat, but it’s the most common neurological condition in the world.”
The focal point of Shin’s research is a compound called isovaline. Among the wealth of compounds found on the Murchison meteorite, isovaline was one of several amino acids — the building blocks of protein, and of life.
“So it seems to suggest that the process to produce those things would be pretty universal,” Shin said. “If you were to find amino acids on a chunk of rock that came in from a million miles away, with the same composition, you think, ‘Maybe something like this could happen somewhere else.’ That’s why an interest evolved with all meteorites, not just Murchison.”
On Sept. 28, 1969, this particular meteorite landed in the town of Murchison, Victoria, from which it draws its name. It has been studied by scientists worldwide ever since its arrival.
But it was only one of a dozen meteorites to land in Victoria during the 1900s, according to the International Society for Meteoritics and Planetary Science.
Daniel P. Glavin and Jeffrey Bada of the Scripps Institution of Oceanography, located at the University of California at San Diego, reported in 2001, “The delivery of amino acids by micrometeorites to the early Earth during the period of heavy bombardment could have been a significant source of the Earth’s prebiotic amino acid inventory, provided that these organic compounds survived atmospheric entry heating.”
According to a 2009 report by Glavin and Jason Dworkin for the National Aeronautics and Space Administration, the measured amount of isovaline in the Murchison meteorite is the largest in any meteorite reported to date. They concluded that the enrichment of isovaline “cannot be the result of interference from other C(5) amino acid isomers present in the samples, analytical biases, or terrestrial amino acid contamination.”
According to Shin, isovaline had been discovered in fungi on Earth in the years following the meteorite’s arrival.
“There was a resurgence about how isovaline is endemic to this world, and whether or not isovaline could be a contamination from dust particles of the meteorite itself,” said Shin. “But, from my understanding, a more recent paper looked at the actual structure of the isovaline in the fungus, and found that it’s not exactly the same. So, either it got contaminated, or mutated in a way, or the fungus was able to produce it…So, the next question is, can it only be found in the meteorite, or can it be produced on Earth?”
Local study
Shin was studying isovaline’s medical potential before he came to Albany Medical Center about two-and-a-half years ago, he said.
“I had done this as my post-doctoral fellowship at Toronto Western Hospital with my mentor, Dr. Peter Carlen, a very prominent epilepsy neurologist,” said Shin. “That was in 2008. When I came here to Albany Med as an assistant professor, I had pursued research with Parkinson’s disease, but I wanted to complete the project I started in Toronto.”
Their findings on isovaline were published in Epilepsia, an international journal that covers the ongoing research in epilepsy treatment. The paper was co-authored with Carlen, and a team of scientists that included Dr. Ernie Puil, a University of British Columbia researcher who had studied the use of isovaline for pain management. It was the pain-related research that made Shin curious about isovaline’s other possible uses.
“Isovaline has a similar structure to glycine, which is a neurotransmitter that effectively quiets down the brain,” Shin said. “They looked at it and saw that, indeed, it could be used as a pain suppressant. For us, though, it was interesting because seizures are characterized as hyperactive, recurrent brain function; if you can quiet down that activity, it could work as an anticonvulsant.”
The relevant characteristic of isovaline is its effect on interneurons, Shin explained.
“Interneurons are inhibitory neurons; they’re the brain cells that keep things quiet,” he said. “Isovaline seems to excite these interneurons, and the end result is that they do a better job of doing what they do. It seems to enhance these quieting neurons, which is kind of consistent with how epilepsy research is going, but we’re not sure exactly what the nuts and bolts are as to how it works.”
After experimenting on rodents, Shin was intrigued by his findings.
“The most pessimistic possible view was that this amino acid would have zero affect on any function in the brain, so, when you undergo a seizure event, the isovaline would do nothing,” said Shin. “But, we wanted to see that it worked like glycine, that it had the potential to quiet down neuro-activity, and we found that it did have anti-convulsive qualities.”
In some cases, the isovaline was able to stop seizures entirely. In other cases, seizures were weakened in their intensity and frequency.
Typically, epilepsy is treated with pharmaceutical drugs, Shin went on.
“There are patients who are given drug therapy, and the majority of them do respond, but there are often complications that occur,” said Shin. “But, 20 to 30 percent of these patients are considered intractable — they don’t respond to the drugs at all — and they might be candidates for resective surgery, where they actually take out a part of the brain that they think is a seizure generator.”
Doctors use a test called an electroencephalogram, or EEG, to measure and record electrical activity in a person’s brain.
“They try to isolate where the origin of the seizures are, and, depending on which part of the brain and which side of the brain it is, whether there’s cost or benefit to take out that piece of the brain,” said Shin. “What we’re hoping is that isovaline could reveal a new class of drugs, a new target. So, instead of using isovaline, we could use something that could be synthesized.”
While his findings are promising with respect to the treatment of epilepsy, Shin said he doubts the use of isovaline as treatment for Parkinson’s disease, “Because the isovaline seems to act by quieting down the brain. Nobody really knows how Parkinson’s works, but one thought is, you don’t have as much activity as you should in some parts of the brain.”
The next step in his epilepsy research, he said, is determining which of the brain’s ion channels is affected by isovaline.
“Our lab does electro-physiology, which looks at ion channels, or pores that conduct ions,” Shin said. “They can conduct current, so you can measure how much ion-channel activity is happening by measuring the electrical activity of that cell. So, we have ideas of what we think is going on, and whether one ion channel is opening and closing,” when isovaline is administered.
So far, the results have kept Shin optimistic. But beyond the use of isovaline on seizure patients lies the question of where this meteorite came from, and how these compounds formed in a place so distant from life as we know it.
“Seeing amino acids in a meteorite that came from light years away, you’d think they were formed in a very similar process as the ones that form here — so, we’re not alone in how things formed,” Shin concluded. “The fact that something from outer space can have an impact on a physiological function here is interesting, because the flipside of that is the possibility that something here could affect something out there.”
—By Zach Simeone