{"id":72993,"date":"2018-06-13T10:35:02","date_gmt":"2018-06-13T14:35:02","guid":{"rendered":"http:\/\/www.bu.edu\/eng\/?p=72993"},"modified":"2023-01-03T16:24:33","modified_gmt":"2023-01-03T21:24:33","slug":"hearts-minds-and-microbubbles","status":"publish","type":"post","link":"https:\/\/www.bu.edu\/eng\/2018\/06\/13\/hearts-minds-and-microbubbles\/","title":{"rendered":"Hearts, Minds, and Microbubbles"},"content":{"rendered":"<h2>Sargent, ENG profs collaborate to prevent strokes that cause dementia<\/h2>\n<div class=\"article three-col nosidebar-story cf\" id=\"post-124359\">\n<div class=\"entry sc\">\n<div class=\"meta\">\n<p><span class=\"byline\">By David Levin, <em><a href=\"http:\/\/www.bu.edu\/today\/2018\/hearts-minds-and-microbubbles\/\">BU Today<\/a><\/em> 3\/6\/18<br \/>\n<\/span><\/p>\n<\/div>\n<div class=\"banner-container banner-has-image\">\n<figure style=\"width: 543px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" src=\"http:\/\/www.bu.edu\/today\/files\/2018\/02\/dimentia_996x664_17-1925-PORTERMORGAN-098.jpg\" class=\"banner\" alt=\"Dr. Kathy Morgan, a professor at Sargent College and Dr. Tyone Porter, pose for a photo\" height=\"355\" width=\"533\" \/><figcaption class=\"wp-caption-text\">BU faculty Tyrone Porter (ME, MSE) and Kathleen Morgan (SAR) are using a $2.5 million grant from the National Institute on Aging to develop a drug, and a delivery system, that may help prevent blood vessels from bursting and causing early-stage dementia. Photo by Jackie Ricciardi<\/figcaption><\/figure>\n<\/div>\n<div class=\"article three-col left cf\" id=\"post-122823\">\n<div class=\"entry sc\">\n<ul>\n<li><strong>Stiffened arteries can cause microbleeds in the brain, possibly leading to dementia<\/strong><\/li>\n<li><strong>A prototype drug might control artery stiffness<\/strong><\/li>\n<li><strong>Microscopic bubbles and ultrasound beams could deliver the drug straight into artery walls<\/strong><\/li>\n<\/ul>\n<hr \/>\n<p>Memory loss in old age starts small, with misplaced keys or wallets. In some people, it can be the sign of a far more serious disorder. Dementia can eventually set in, robbing people of the memories of faces, names, and important events. It\u2019s devastating for both patients and family members\u2014and it\u2019s distressingly common. According to the World Health Organization, more than 47 million people currently suffer from dementia worldwide.<\/p>\n<p>While Alzheimer\u2019s disease is probably the most well-known form, dementia also comes in other, lesser-known varieties, like vascular dementia\u2014caused when tiny blood vessels burst in the brain, leading to microstrokes and minute bleeds. The resulting condition is closely linked with other age-related memory disorders.<\/p>\n<p>\u201cI suspect that vascular dementia and Alzheimer\u2019s are really just two different angles on the same disease,\u201d says\u00a0<a href=\"https:\/\/www.bu.edu\/sargent\/profile\/kathleen-morgan-ph-d-2\/\">Kathleen Morgan<\/a>, a Sargent College of Health &amp; Rehabilitation Sciences professor of health sciences. \u201cThere are plaques in the brain tissue of Alzheimer\u2019s patients that are visible at autopsy, but we know that if you have them, you\u2019ll probably see evidence of microbleeds as well.\u201d<\/p>\n<div id=\"attachment25024\" class=\"wp-caption aligncenter\">\n<figure id=\"attachment_25024\" aria-describedby=\"caption-attachment-25024\" style=\"width: 560px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" src=\"http:\/\/www.bu.edu\/research\/files\/2017\/12\/outofocus_17-1925-PORTERMORGAN-126.jpg\" alt=\"Photo by Jackie Ricciardi\" class=\"wp-image-25024 size-full\" height=\"708\" width=\"550\" \/><figcaption id=\"caption-attachment-25024\" class=\"wp-caption-text\">Morgan holds a vial containing a mouse brain removed from an aged mouse. It\u2019s comparable to the brain of a 75-year-old human. She and collaborator Tyrone Porter are using mice to test a prototype drug that could prevent stroke-causing microbleeds. Photo by Jackie Ricciardi<\/figcaption><\/figure>\n<\/div>\n<p>And if burst blood vessels are implicated in early-stage dementia, Morgan says, it may be possible to stop that damage before it starts. With a $2.5 million grant from the\u00a0<a href=\"https:\/\/www.nia.nih.gov\/\">National Institute on Aging<\/a>\u00a0(NIA), she is examining a synthetic prototype drug that could prevent microbleeds in mouse brains. She\u2019s joining forces with\u00a0Tyrone Porter, an associate professor of\u00a0mechanical engineering and associate professor of materials science and engineering, are working across disciplines to develop a new delivery system for the drug. Their solution uses a novel system of microbubbles\u2014tiny bubbles of inert gas smaller than capillaries\u2014along with a focused ultrasound beam to help push the drug into a very specific part of the body: the large blood vessels next to the heart.<\/p>\n<p>Most brain bleeds, Morgan says, actually start in the aorta, the body\u2019s largest artery, which connects directly to the heart. With each beat, the heart exerts enormous amounts of pressure straight onto that conduit, which is made of smooth muscle cells that expand and contract like a rubber hose as blood flows past them. \u201cThose smooth muscle cells are very important for controlling the pressure of your vascular system on a beat-to-beat basis,\u201d she says.<\/p>\n<p>In younger bodies\u2014both mouse and human\u2014smooth muscle in the aorta expands with each beat, acting as a sort of shock absorber for the pressure coming out of the heart. In older bodies, though, it becomes gradually less elastic, meaning that the energy of each pulse travels farther through the vascular system. If the aorta becomes stiff enough, blood can surge at high pressure straight into tiny, sensitive blood vessels in the brain, which may burst under the strain.<\/p>\n<p>Morgan is developing new ways to reverse the stiffening of arteries. If she can restore some of the aorta\u2019s elasticity, she reasons, it may be possible to prevent new microbleeds. To test this idea, she\u2019s concocted a new peptide\u2014a small chain of amino acids\u2014that can control smooth muscle stiffness.<\/p>\n<figure id=\"attachment_25061\" aria-describedby=\"caption-attachment-25061\" style=\"width: 560px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" src=\"http:\/\/www.bu.edu\/research\/files\/2017\/12\/image001.png\" alt=\"image001\" class=\"wp-image-25061 size-full\" height=\"508\" width=\"550\" \/><figcaption id=\"caption-attachment-25061\" class=\"wp-caption-text\">Morgan and Porter\u2019s drug delivery system. The scientists attach the drug to microbubbles smaller than capillaries and use a focused ultrasound beam to guide the bubbles and then burst them, delivering the drug directly into smooth muscle cells. Eventually, they hope their system may be used to deliver drugs to the large blood vessels next to the heart. Illustration by Tyrone Porter<\/figcaption><\/figure>\n<p>In smooth muscle tissue, she says, elasticity is determined in part by two types of long, stringy molecules called actin and myosin, which form a web inside each cell. As the two strands latch onto each other, they restrict the cell\u2019s movement, stiffening its structure. \u201cIt\u2019s a bit like a Chinese finger trap,\u201d says Morgan. \u201cThe harder you tug on actin, the harder it clamps down.\u201d The peptide her team has created, however, can effectively stop this process in its tracks by binding to the molecules, preventing them from grabbing onto their counterparts in the first place. As a result, the cell remains relaxed and supple. Morgan can control how stiff or loose the tissue gets by controlling the amount of peptide she administers.<\/p>\n<p>The challenge is delivering those molecules directly to the smooth muscle inside a living aorta. Unlike other drugs, releasing this one system-wide\u2014or even artery-wide\u2014could be disastrous. \u201cSmooth muscle tissue isn\u2019t just in the aorta. It\u2019s in your vascular system, urinary tract, uterus, lung tissue, and digestive system,\u201d she notes. \u201cIf the peptides got into those tissues, it could cause incontinence, premature labor, all sorts of awful things.\u201d<\/p>\n<p>To get the drug exactly where it\u2019s needed, however, you first have to dig into the artery itself.<\/p>\n<p>\u201cThe cells we need to target don\u2019t come in contact with flowing\u00a0blood. They\u2019re behind a layer or two of other cells and connective tissue in the blood vessel walls,\u201d says Porter. To break through those layers and deliver the drug directly to smooth muscle cells, he\u2019s attaching Morgan\u2019s peptides directly to the outside of each microbubble. Focused ultrasound can be used to push the microbubbles toward the aortic wall and pop them to release the peptide. The popping process also subtly and reversibly disrupts the lining of the aorta, making the blood vessel wall temporarily permeable. \u201cOnce that happens, the peptide can flow directly into the spaces that open up in the vessel wall and go straight into the smooth muscle tissue,\u201d he says.<\/p>\n<p>These microbubbles themselves are simple to make, Porter adds, and the FDA has already approved them for use. \u201cMicrobubbles have been used for years as contrast agents for ultrasound. They scatter sound\u00a0much better than tissue, so they\u2019re used to distinguish blood from the chambers in heart and surrounding muscle,\u201d he says. They\u2019re also tiny enough to fit through the smallest blood vessels in the body and eventually disappear as the gas, which is harmless, escapes into the blood and is expelled out of the body through the lungs.<\/p>\n<p>In addition to being relatively safe, the clinical advantage of this approach is that it can be done with a standard ultrasound probe commonly used in a cardiac echo test. Using a low-powered ultrasound beam, a technician can track where the bubbles are going, then pop them at a specific location by simply turning up the strength of the beam. Existing ultrasound tools \u201ccan focus the beam down to the millimeter, so it\u2019s extremely accurate,\u201d Porter says.<\/p>\n<p>Until now, Morgan has been able to test her peptide and its new delivery system only on smooth muscle cells in a petri dish. With the new NIA grant, however, she and her collaborators are looking to scale up their research, and they will use their approach for the first time on a living animal.<\/p>\n<p>\u201cMy earlier work was just on the fundamental mechanics of these peptides. Moving into a whole mouse is a big leap for someone used to sitting at a bench dealing with cells,\u201d she says with a laugh. \u201cThe people I\u2019ve connected with here at BU make it feasible, though. That\u2019s how you get basic discoveries translated into practical ones\u2014you have lots of scientists working in parallel. You need teams\u00a0instead of a single investigator.\u201d<\/p>\n<p><em>David Levin can be reached at\u00a0<a href=\"mailto:delevin@bu.edu\">delevin@bu.edu<\/a>.<\/em><\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Prof. Porter wins $2.5 million grant from the NIA to develop a drug and a delivery system. Prof. Porter is partnering with Prof. Morgan.<\/p>\n","protected":false},"author":14791,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[236,909,245],"tags":[490,491,492,244,493,494,495,496],"_links":{"self":[{"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/posts\/72993"}],"collection":[{"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/users\/14791"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/comments?post=72993"}],"version-history":[{"count":2,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/posts\/72993\/revisions"}],"predecessor-version":[{"id":135267,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/posts\/72993\/revisions\/135267"}],"wp:attachment":[{"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/media?parent=72993"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/categories?post=72993"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/tags?post=72993"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}