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<\/a>Ed Meloni ’91 speaks to students in Professor of Neuroscience Nancy Koven’s course on embodied cognition during his mid-March visit as the College Key Distinguished Alumnus in Residence. (Phyllis Graber Jensen\/Bates College)<\/p><\/div>\n
In any given year, more than eight million Americans suffer from PTSD, which develops in some people who have experienced a traumatic personal event. Most people probably know something about PTSD through its depiction in popular culture, particularly war movies. Early on, in 1946, there was the post-World War II movie Best Years of Their Lives<\/i>, then movies like Coming Home<\/i>, Born on the Fourth of July<\/i>, and The Hurt Locker<\/i>, all of which portray PTSD sufferers.<\/p>\n
The nightmares and flashbacks \u2014 two among many symptoms of PTSD<\/a> \u2014 feel very real. In one way, they are, and that\u2019s the key to Meloni\u2019s research on xenon gas as a potential treatment.<\/p>\n Meloni is a researcher<\/a> at Harvard-affiliated McLean Hospital, where he works alongside Bill Carlezon ’86<\/a>, director of the hospital\u2019s Behavioral Genetics Laboratory. During his visit to Bates in March as the College Key\u2019s Distinguished Alumnus in Residence, Meloni joined neuroscience classes, met with students, and delivered an evening lecture. He and I spoke for about an hour.<\/p>\n Researchers, Meloni explained, used to believe that \u201crecalling a memory was like reading a file.\u201d It was read, then put back. \u201cWe thought memories were immutable.\u201d Meloni and other scientists have shown that\u2019s not the case. \u201cOur memories can be changed; new information can be integrated.\u201d<\/p>\n (In fact, Meloni says, \u201cour memories are probably not faithful representations of what really happened,\u201d which has great implications for the reliability of crime eyewitnesses, a field of research by Bates psychology professor Amy Douglass<\/a>.)<\/p>\n This process of memory retrieval and updating is known as reconsolidation, and Meloni is an expert in the field. In 2014, he and colleagues at McLean showed that xenon gas can block the reconsolidation of fearful memories in lab rats, effectively eliminating the fear. The discovery garnered national attention<\/a> for its promise to end PTSD suffering.<\/p>\n Now, the promise is getting close to reality.<\/p>\n PTSD can affect military service members who experience a traumatic event in combat. (U.S. Air Force photo\/Tech. Sgt. Nadine Barclay)<\/p><\/div>\n For a discovery that could bear directly on human life, the route to finding it was \u201cindirect,\u201d Meloni says. \u201cIt was chance and serendipity.\u201d (And, we would add, also some creative thinking on his part.)<\/p>\n As the story goes, a colleague of Meloni’s was presenting research data at a conference, where he learned that a medical gas company was interested in providing a device that would allow scientists to use xenon gas in their rat-model experiments on neurodegenerative diseases.<\/p>\n “You can\u2019t just get a rat to put a mask on.\u201d<\/p><\/blockquote>\n The device was needed because “gases are hard to work with\u201d in research that uses a rat model, Meloni explains. \u201cThere are a lot of intricacies with gas delivery. It\u2019s not as simple as giving a drug. You can\u2019t just get a rat to put a mask on.\u201d<\/p>\n So the medical gas company funded a research apparatus at McLean, the first of its kind in the world, to test the effects of xenon gas on a rat model.<\/p>\n In terms of its general medical use, xenon is hardly new; though expensive, it\u2019s considered a superior anesthetic and is used in diagnostic imaging. And in recent years, new research indicated that xenon could be “neuroprotective” in the brain, Meloni says, a general term meaning that it might protect nerve cells from the kind of damage found in neurodegenerative diseases and traumatic brain injuries, such as concussion.<\/p>\n The unique research device in place, Meloni was initially part of an unrelated study that yielded \u201ca strong signal\u201d that xenon was indeed neuroprotective. Specifically, xenon is an \u201cNMDA receptor antagonist\u201d that protects the brain from an insult, glutamate excitotoxicity.<\/p>\n That led Meloni to wonder: If xenon is an NMDA receptor antagonist, it should block learning and memory because that\u2019s the outcome when animals are given drugs that block the NMDA receptor. \u201cThey don\u2019t learn,\u201d he says. \u201cOr, they stop fearing something they learned.\u201d<\/p>\n \u201cI just wanted to test that,\u201d Meloni says. And among myriad tests involving xenon, rats, and fear, three results proved pivotal. First, they found that giving xenon gas to rats prevented them from developing a certain fear, in this case the fear of a mild shock. \u201cWe blocked the learning<\/i> of fear,\u201d Meloni recalls.<\/p>\n \u201cI was floored,\u201d Meloni says. \u201cThat was the home run.\u201d<\/p><\/blockquote>\n At this point, Meloni\u2019s expertise in memory reconsolidation kicked in. He thought, \u201cWhat if the animals are already<\/i> afraid? Can xenon block a memory that was already there?\u201d<\/p>\n So Meloni decided to pair the administration of gas with the reactivation of a fearful memory (in this case, a mild shock) that the rats had learned by Pavlovian association. When the fear was reactivated, in this case by the sound of a tone previously paired with the shock, the rats were immediately exposed to xenon gas. Tested a few days later \u2014 even weeks later \u2014 \u00a0they did not show fear when the tone was presented.<\/p>\n \u201cI was floored,\u201d Meloni says. \u201cThat was the home run.\u201d<\/p>\n Xenon gas fills a discharge tube shaped like the element\u2019s atomic symbol. (Photograph by Pslawinski [CC BY-SA 2.5], via Wikimedia Commons)<\/p><\/div>Refining their findings, the researchers gave xenon to fear-conditioned rats but did not reactivate their fear by presenting the tone. Tested a few days later, the rats remained fearful. \u201cThat suggested that pairing the gas administration with the reactivation of the memory was critical for this whole thing to work,\u201d Meloni says. \u201cRight away I knew we could translate it to PTSD.\u201d<\/p>\n Last summer, the U.S. Patent and Trademark Office gave Meloni and fellow researcher Marc Kaufman a \u201cpatent allowance\u201d<\/a> \u2014 essentially a patent approval \u2014 for using xenon gas to treat PTSD. The biotech firm Nobilis Therapeutics has licensed the patent and seeks to develop a hand-held medical device for self-administration of xenon.<\/p>\n The hand-held device \u201cis absolutely critical,\u201d Meloni says. \u201cIf a medical professional identifies that you might benefit from xenon therapy, you want to administer it as soon as the traumatic memory is reactivated, which happens \u201corganically, out in the real world,\u201d Meloni notes, in nightmares, flashbacks, or by exposure to cues that remind the patient of the traumatic event, much like when the tone is presented to the fear-conditioned rats. \u201cThat\u2019s when we think you\u2019re going to get the most therapeutic effect.\u201d<\/p>\n Of course, FDA approval is still required. \u201cUp until now, there\u2019s been no FDA-approved way to administer xenon gas aside from an elaborate anesthesia machine\u201d in a medical setting, Meloni explains. At the moment, Meloni and colleagues are awaiting the go-ahead from the FDA to begin clinical human trials at McLean.<\/p>\n John Kelsey \u201cactivated my brain,\u201d Meloni says.<\/p><\/blockquote>\n If Meloni has shown smart and creative thinking in his xenon research, it\u2019s safe to say those abilities were cultivated by his Bates professors. A student in the days before Bates developed its neuroscience program<\/a>, Meloni designed his own interdisciplinary major to combine interests in biology and psychology.<\/p>\n Meloni wanted to study the brain, and \u201cpsychology alone didn\u2019t quite fit the bill because the brain is a biological organism. Everything of the mind is derived from the biology of the brain \u2014 our cognition, how we feel \u2014 so I went with biology of the brain plus psychology: biopsychology.\u201d<\/p>\n On the bio side, mentors included Pam Baker \u201969, now retired, and Lee Abrahamsen. On the psych side, it was John Kelsey. (Also retired, Kelsey was recently honored with the creation of a new endowed professorship in his name, the John E. Kelsey Professorship in Neuroscience.)<\/p>\n<\/a><\/a>