{"id":140390,"date":"2023-05-26T09:15:08","date_gmt":"2023-05-26T13:15:08","guid":{"rendered":"http:\/\/www.bu.edu\/eng\/?p=140390"},"modified":"2023-08-22T15:46:52","modified_gmt":"2023-08-22T19:46:52","slug":"attacking-fatty-buildup-at-the-source","status":"publish","type":"post","link":"https:\/\/www.bu.edu\/eng\/2023\/05\/26\/attacking-fatty-buildup-at-the-source\/","title":{"rendered":"Attacking Fatty Buildup at the Source"},"content":{"rendered":"

Grinstaff team\u2019s nanodrug might be first to solve vexing problem in liver<\/strong><\/h3>\n

By Patrick L. Kennedy<\/p>\n

A novel nanotechnology promises to be the first therapeutic to directly target the liver in the battle against a disease that afflicts roughly a quarter of the global population. The new treatment was reported in Nature Communication <\/em>by Professor Mark Grinstaff (BME, Chemistry, MSE, MED), Xue Han (BME), and an international team of scientists and engineers.<\/p>\n

When the liver is firing on all cylinders, it cleans out degraded materials from the blood, such as fat and proteins that are no longer needed. This process\u2014one of the liver\u2019s many useful functions\u2014is called autophagy, and it\u2019s carried out by lysosomes, tiny organelles within the liver cells.<\/p>\n

But in 20 to 30 percent of people around the world, the lysosomes stop doing their job, for reasons not fully understood. Fat droplets start to clog and swell the liver, causing pain in the abdomen, as well as fatigue. The condition is known as non-alcoholic fatty liver disease (NAFLD), because it\u2019s a liver ailment that is not related to alcohol abuse. Unchecked, it can cause cirrhosis and even liver failure.<\/p>\n

\"\"
Mark Grinstaff (BME, Chemistry, MSE, MED)<\/em><\/figcaption><\/figure>\n

\u201cToday, there are not enough transplant livers to meet the demand,\u201d says Grinstaff, who is a William Fairfield Warren Distinguished Professor, the most prestigious title BU bestows on faculty.<\/p>\n

Because NAFLD is so prevalent, a variety of solutions have been proposed, and some have made it to market, but none of them directly solve the problem by removing the fat. \u201cWe wondered whether there were ways we could control or alter the biology of the liver so that it could process the fat,\u201d says Grinstaff.<\/p>\n

Grinstaff\u2019s team sought to understand how fat is metabolized in and removed from the liver cell under ordinary circumstances; then they set about replicating that process with synthetic nanoparticles.<\/p>\n

\u201cWe delivered a nanoparticle that basically rejuvenated that process\u2014kick-started it and got it back up and running, so that it removes the fat,\u201d says Grinstaff.<\/p>\n

These acidifying nanoparticles (AcNPs) reactivate the lazy lysosomes, increasing the liver\u2019s acidity to healthy levels and reversing the fatty buildup, as the researchers reported in Nature Communication.<\/em> \u201cThat was the cool part, being able to actually see it work in the cell culture, and then in the animal model,\u201d Grinstaff says.<\/p>\n

In addition to Han, Grinstaff\u2019s team included Jialiu Zeng (ENG\u201920), who was a BME PhD student and is now the Presidential Postdoctoral Fellow at Lee Kong Chian School of Medicine, Nanyang Technological University in Singapore; and Orian Shirihai, a former associate professor at the Chobanian & Avedisian School of Medicine who is now the chair of endocrinology, diabetes and hypertension at UCLA.<\/p>\n

\u201cIt\u2019s a highly convergent project,\u201d says Grinstaff. \u201cLots of different ways of thinking came together to address this problem,\u201d including Shirihai\u2019s expertise in metabolic diseases. \u201cSpeaking with clinicians gives you insights that you just don\u2019t have as an engineer.\u201d<\/p>\n

Grinstaff and Shirihai started working on the project with seed funding from a pilot grant project of the Boston University Nanotechnology Innovation Center (BUnano). The mission of BUnano is to support collaborative research in nanotechnology and facilitate the translation of BU faculty\u2019s scientific discoveries to the market.<\/p>\n

A fellow of the National Academy of Inventors, Grinstaff holds more than 200 patents or pending patent applications. \u201cIf things continue on a positive path, I think it would be wonderful to get to the first-in-human clinical trials within five years,\u201d Grinstaff says. \u201cThis is a disease that is extremely common, it needs solutions, and there are not a lot of solutions out there.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"

A novel nanotechnology promises to be the first therapeutic to directly target the liver in the battle against a disease that afflicts roughly a quarter of the global population.<\/p>\n","protected":false},"author":2662,"featured_media":140392,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[236,257,899,535,1034,909,1],"tags":[1010,656,839],"_links":{"self":[{"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/posts\/140390"}],"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\/2662"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/comments?post=140390"}],"version-history":[{"count":3,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/posts\/140390\/revisions"}],"predecessor-version":[{"id":140399,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/posts\/140390\/revisions\/140399"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/media\/140392"}],"wp:attachment":[{"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/media?parent=140390"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/categories?post=140390"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/tags?post=140390"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}