first_imgMultiple copies of a four-armed peptide wrap around lipids to create particles that mimic the behavior of HDL, the “good” cholesterol. A new drug candidate designed to mimic the body’s “good” cholesterol shows a striking ability in mice to lower cholesterol levels in the blood and dissolve artery-clogging plaques. What’s more, the compound works when given orally, rather than as an injection. If the results hold true in humans—a big if, given past failures at transferring promising treatments from mice—it could provide a new way to combat atherosclerosis, the biggest killer in developed countries.Although doctors already have effective cholesterol-lowering agents, such as statins, at their disposal, there’s room for improvement. Statins have significant side effects in some people and don’t always reduce cholesterol enough in others. “There is still plenty of heart disease out there even among people who take statins,” says Godfrey Getz, an experimental pathologist at the University of Chicago in Illinois.For that reason, researchers around the globe are searching for novel drugs that affect cholesterol levels in one of two ways. The first has been to reduce levels of low-density lipoprotein (LDL), commonly known as bad cholesterol, which has been associated with higher heart disease risk. This is the goal of statins, which block an enzyme involved in cholesterol production. The second strategy is to increase levels of good cholesterol, or high-density lipoprotein (HDL), which seems to boost heart health in people who have a lot of it. But producing HDL-raising drugs that prevent heart disease has proven difficult. In the body, a large protein called apolipoprotein A-I (apoA-I) wraps around fatty lipid molecules to create HDL particles that sop up LDL and ferry it to the liver where it is eliminated. So for several decades researchers have been designing and testing small protein fragments called peptides to see if they could mimic the behavior of apoA-I. One such peptide, known as 4F, did not reduce serum cholesterol levels, but it did shrink arterial plaques in mice, rabbits, and monkeys. And in an early clinical trial by researchers at Bruin Pharma Inc. in Beverly Hills, California, that was designed only to measure its safety in people, 4F didn’t appear to show any beneficial effect.  Sign up for our daily newsletterGet more great content like this delivered right to you!Country *AfghanistanAland IslandsAlbaniaAlgeriaAndorraAngolaAnguillaAntarcticaAntigua and BarbudaArgentinaArmeniaArubaAustraliaAustriaAzerbaijanBahamasBahrainBangladeshBarbadosBelarusBelgiumBelizeBeninBermudaBhutanBolivia, Plurinational State ofBonaire, Sint Eustatius and SabaBosnia and HerzegovinaBotswanaBouvet IslandBrazilBritish Indian Ocean TerritoryBrunei DarussalamBulgariaBurkina FasoBurundiCambodiaCameroonCanadaCape VerdeCayman IslandsCentral African RepublicChadChileChinaChristmas IslandCocos (Keeling) IslandsColombiaComorosCongoCongo, The Democratic Republic of theCook IslandsCosta RicaCote D’IvoireCroatiaCubaCuraçaoCyprusCzech RepublicDenmarkDjiboutiDominicaDominican RepublicEcuadorEgyptEl SalvadorEquatorial GuineaEritreaEstoniaEthiopiaFalkland Islands (Malvinas)Faroe IslandsFijiFinlandFranceFrench GuianaFrench PolynesiaFrench Southern TerritoriesGabonGambiaGeorgiaGermanyGhanaGibraltarGreeceGreenlandGrenadaGuadeloupeGuatemalaGuernseyGuineaGuinea-BissauGuyanaHaitiHeard Island and Mcdonald IslandsHoly See (Vatican City State)HondurasHong KongHungaryIcelandIndiaIndonesiaIran, Islamic Republic ofIraqIrelandIsle of ManIsraelItalyJamaicaJapanJerseyJordanKazakhstanKenyaKiribatiKorea, Democratic People’s Republic ofKorea, Republic ofKuwaitKyrgyzstanLao People’s Democratic RepublicLatviaLebanonLesothoLiberiaLibyan Arab JamahiriyaLiechtensteinLithuaniaLuxembourgMacaoMacedonia, The Former Yugoslav Republic ofMadagascarMalawiMalaysiaMaldivesMaliMaltaMartiniqueMauritaniaMauritiusMayotteMexicoMoldova, Republic ofMonacoMongoliaMontenegroMontserratMoroccoMozambiqueMyanmarNamibiaNauruNepalNetherlandsNew CaledoniaNew ZealandNicaraguaNigerNigeriaNiueNorfolk IslandNorwayOmanPakistanPalestinianPanamaPapua New GuineaParaguayPeruPhilippinesPitcairnPolandPortugalQatarReunionRomaniaRussian FederationRWANDASaint Barthélemy Saint Helena, Ascension and Tristan da CunhaSaint Kitts and NevisSaint LuciaSaint Martin (French part)Saint Pierre and MiquelonSaint Vincent and the GrenadinesSamoaSan MarinoSao Tome and PrincipeSaudi ArabiaSenegalSerbiaSeychellesSierra LeoneSingaporeSint Maarten (Dutch part)SlovakiaSloveniaSolomon IslandsSomaliaSouth AfricaSouth Georgia and the South Sandwich IslandsSouth SudanSpainSri LankaSudanSurinameSvalbard and Jan MayenSwazilandSwedenSwitzerlandSyrian Arab RepublicTaiwanTajikistanTanzania, United Republic ofThailandTimor-LesteTogoTokelauTongaTrinidad and TobagoTunisiaTurkeyTurkmenistanTurks and Caicos IslandsTuvaluUgandaUkraineUnited Arab EmiratesUnited KingdomUnited StatesUruguayUzbekistanVanuatuVenezuela, Bolivarian Republic ofVietnamVirgin Islands, BritishWallis and FutunaWestern SaharaYemenZambiaZimbabweI also wish to receive emails from AAAS/Science and Science advertisers, including information on products, services and special offers which may include but are not limited to news, careers information & upcoming events.Required fields are included by an asterisk(*)M. Reza Ghadiri, a chemist at the Scripps Research Institute in San Diego, California, and his colleagues took a slightly different tack, creating a peptide that mimics another part of the apoA-I protein than 4F does. Initial in vitro studies suggested the peptide formed HDL-like particles and sopped up LDL, an encouraging result that prompted them to push it further. Ghadiri and his Scripps colleagues have now tested their compound in mice that develop artery clogging plaques when fed a Western-style high-fat diet. One group of animals received the peptide intravenously. For another group, the researchers simply added the compound to the animals’ water, a strategy they considered unlikely to work, because the gut contains high amounts of proteases designed to chop proteins apart. To their surprise, in both groups, serum cholesterol levels dropped 40% from their previous levels within 2 weeks of starting to take the drug. And by 10 weeks, the number of artery-clogging lesions had been reduced by half, the team reports in the October issue of the Journal of Lipid Research. What remains puzzling, however, is that Ghadiri and his colleagues did not detect their peptides in the blood of their test animal. Ghadiri says this suggests that the new peptide may work by removing cholesterol precursors in the gut before they enter the bloodstream.“It’s a very interesting result,” Getz says. But he cautions that the work has been tested only in animals, and many therapies—including the closely related 4F peptide—fail to transfer to humans. That said, Getz notes that some of the initial promising results with this peptide and other apoA-I mimics offer hope that researchers may soon come up with novel drugs capable of dissolving artery-clogging plaques before they can wreak their havoc. Y.Zhao et al., J. Am. Chem. Soc., 135 (2013) last_img read more

first_img Inquiry into Melco Resorts acquisition to determine whether Crown Resorts still suitable to hold NSW gaming license Melco Resorts defers acquisition of second tranche of Crown shares until conclusion of regulatory inquiry Hong Kong Jockey Club cites “serious integrity concerns” in complaint over Crown Resorts-owned betting exchange Load More RelatedPosts Australian casino operator Crown Resorts has scored a major win for its AU$2.2 billion development at Sydney’s Barangaroo precinct after the Supreme Court of NSW found that the Barangaroo Delivery Authority (BDA) had breached an agreement between the two regarding lines of sight.The ruling comes four months after Crown commenced legal proceedings against the BDA in relation to a proposed development within the same area that threatens the expansive views of Sydney Harbour that Crown Sydney is set to enjoy once complete in 2021. Crown and its development partner Lendlease had previously signed a Crown Development Agreement with the BDA based on the original concept plan for the area which, among other stipulations, required the BDA to “negotiate in good faith” with both companies on any proposed developments that differed from the concept plan.In a judgement delivered on Friday, the Supreme Court ruled that the BDA, “has breached the development agreements between it, Crown Sydney Property and two Lendlease parties.“This was because the Authority had considered various bids to develop Central Barangaroo without first discussing and negotiating, with Crown and Lendlease, ways to retain the sight lines that the Crown and Lendlease buildings would otherwise enjoy to the Harbour Bridge and Opera House.”The court described the views as being “of great value to Crown and Lendlease respectively.”Justice Robert MacDougall is set make his orders in the case on Monday.When complete, Crown Sydney will stand 271-meters tall and boast a six-star hotel, Sydney’s most expensive residential apartments and a casino designated exclusively for VIPs.Barangaroo will also make Crown the only company operating casinos in each of Australia’s two biggest cities, Sydney and Melbourne.last_img read more