{"id":6708,"date":"2026-03-09T20:07:28","date_gmt":"2026-03-09T17:07:28","guid":{"rendered":"https:\/\/dmdwarrior.com\/?p=6708"},"modified":"2026-03-09T20:09:10","modified_gmt":"2026-03-09T17:09:10","slug":"tenaya-tn-301-beats-givinostat-in-improving-dmd-muscle-function","status":"publish","type":"post","link":"https:\/\/dmdwarrior.com\/tr\/tenaya-tn-301-beats-givinostat-in-improving-dmd-muscle-function\/","title":{"rendered":"Tenaya'n\u0131n TN-301 \u00dcr\u00fcn\u00fc, DMD Kas Fonksiyonunu \u0130yile\u015ftirme Konusunda Givinostat'tan Daha \u0130yi Olabilir"},"content":{"rendered":"<p class=\"wp-block-paragraph\"><strong>Tenaya Therapeutics, Kas Distrofisi Derne\u011fi&#039;nin 2026 Klinik ve Bilimsel Konferans\u0131&#039;nda (MDA 2026), \u015firketin olduk\u00e7a se\u00e7ici HDAC6 inhibit\u00f6r\u00fc olan TN-301&#039;i de\u011ferlendiren umut verici preklinik veriler sundu.<\/strong> Duchenne kas distrofisi (DMD) in vitro ve in vivo modellerinde, TN-301 kas performans\u0131n\u0131 iyile\u015ftirdi ve DMD kardiyomiyopatisinin temel etkenlerini d\u00fczeltti.<\/p>\n\n\n\n<div class=\"wp-block-rank-math-toc-block\" id=\"rank-math-toc\"><h2>\u0130\u00e7indekiler<\/h2><nav><ul><li><a href=\"#dmd-cardiomyopathy-and-muscle-degeneration\">DMD Kardiyomiyopati ve Kas Dejenerasyonu<\/a><\/li><li><a href=\"#tn-301-vs-givinostat\">TN-301 ile Givinostat Kar\u015f\u0131la\u015ft\u0131rmas\u0131<\/a><\/li><li><a href=\"#what-is-tn-301\">TN-301 nedir?<\/a><\/li><\/ul><\/nav><\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>TN-301, Tenaya&#039;n\u0131n g\u00fc\u00e7l\u00fc ve son derece se\u00e7ici k\u00fc\u00e7\u00fck molek\u00fcll\u00fc HDAC6 inhibit\u00f6r\u00fcd\u00fcr ve iltihab\u0131, metabolik ve mitokondriyal d\u00fczensizli\u011fi ve fibrozisi azaltman\u0131n yan\u0131 s\u0131ra otofajiyi iyile\u015ftirme gibi \u00e7ok y\u00f6nl\u00fc bir etki mekanizmas\u0131na sahiptir; bu da nadir veya yayg\u0131n kalp, metabolik, kas ve akci\u011fer hastal\u0131klar\u0131nda potansiyel fayda sa\u011flayabilir.<\/strong> Sa\u011fl\u0131kl\u0131 yeti\u015fkinlerde yap\u0131lan Faz 1 g\u00fcvenlik \u00e7al\u0131\u015fmas\u0131nda, TN-301 geni\u015f bir doz aral\u0131\u011f\u0131nda genel olarak iyi tolere edildi ve ciddi yan etkiler veya dozu s\u0131n\u0131rlayan toksisite g\u00f6stermedi. Bu profile dayanarak, Tenaya, daha \u00f6nce yay\u0131nlanan, ejeksiyon fraksiyonu korunmu\u015f kalp yetmezli\u011fi (HFpEF) ve genetik dilate kardiyomiyopati ile ilgili preklinik sonu\u00e7lar\u0131yla desteklenen, potansiyel olarak ilgi \u00e7ekici birka\u00e7 endikasyon belirledi.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"dmd-cardiomyopathy-and-muscle-degeneration\">DMD Kardiyomiyopati ve Kas Dejenerasyonu<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Bug\u00fcn MDA 2026&#039;da yap\u0131lan sunum, TN-301&#039;in DMD kardiyomiyopatisi ve kas dejenerasyonundaki potansiyelini vurgulayarak bu ara\u015ft\u0131rma alan\u0131na katk\u0131da bulunuyor.<\/strong> Tenaya, TN-301&#039;i hastalar \u00fczerinde klinik \u00e7al\u0131\u015fmalara do\u011fru ilerletmeyi planl\u0131yor ve bug\u00fcne kadar belirlenen en umut vadeden potansiyel endikasyonlar aras\u0131nda HFpEF ve DMD yer al\u0131yor.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u201cTenaya Therapeutics Ara\u015ft\u0131rma K\u0131demli Ba\u015fkan Yard\u0131mc\u0131s\u0131 Dr. Kathy Ivey, \u201dDMD ile ili\u015fkili kardiyomiyopati, DMD&#039;li bireyler aras\u0131nda en yayg\u0131n \u00f6l\u00fcm nedenidir ve bak\u0131mda kaydedilen ilerlemelere ra\u011fmen, hem iskelet kas\u0131 atrofisini hem de kalp fonksiyon kayb\u0131n\u0131 ele alabilecek tedavilere y\u00f6nelik kar\u015f\u0131lanmam\u0131\u015f b\u00fcy\u00fck bir ihtiya\u00e7 bulunmaktad\u0131r\u201c dedi. \u2019DMD ile ili\u015fkili kardiyomiyopati ve iskelet kas\u0131 dejenerasyonunun bir\u00e7ok etkeninin TN-301&#039;in \u00e7ok y\u00f6nl\u00fc etki mekanizmas\u0131yla \u00f6rt\u00fc\u015ft\u00fc\u011f\u00fcn\u00fc fark ederek, bir dizi \u00e7al\u0131\u015fma y\u00fcr\u00fctt\u00fck ve TN-301&#039;in onayl\u0131 ajan givinostat&#039;tan daha iyi performans g\u00f6sterdi\u011fini, mdx farelerinde kas performans\u0131n\u0131 vah\u015fi tip seviyelerine geri getirirken ayn\u0131 zamanda DMD ile ili\u015fkili kardiyomiyosit kusurlar\u0131n\u0131 da d\u00fczeltti\u011fini bulduk.\u201d<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">T\u00fcm HDAC inhibit\u00f6rlerini i\u00e7eren givinostat, ABD ve AB&#039;de DMD tedavisi i\u00e7in onaylanm\u0131\u015ft\u0131r ve 4 Basamakl\u0131 Merdiven T\u0131rmanma Testi (4SC) ve Kuzey Y\u0131ld\u0131z\u0131 Ambulatuvar De\u011ferlendirmesi (NSAA) ile klinik olarak g\u00f6sterildi\u011fi \u00fczere, DMD hastalar\u0131nda iskelet kas\u0131 gerilemesini yava\u015flatt\u0131\u011f\u0131 kan\u0131tlanm\u0131\u015ft\u0131r. <strong>Ancak, trombositopeni gibi yan etkiler ve QT uzamas\u0131 riski nedeniyle kullan\u0131m\u0131 s\u0131n\u0131rl\u0131d\u0131r; bu dezavantajlar TN-301&#039;in Faz 1 \u00e7al\u0131\u015fmas\u0131nda klinik olarak g\u00f6zlemlenmemi\u015ftir.<\/strong> Tenaya ara\u015ft\u0131rmac\u0131lar\u0131, TN-301&#039;in DMD&#039;de hem iskelet kas\u0131 patolojisini hem de kardiyomiyopatiyi geciktirebilece\u011fi veya tersine \u00e7evirebilece\u011fi hipotezini test etmek i\u00e7in TN-301&#039;i givinostat ile kar\u015f\u0131la\u015ft\u0131ran \u00e7al\u0131\u015fmalar y\u00fcr\u00fctt\u00fcler. MDA 2026&#039;da sunulan temel bulgular \u015funlard\u0131r:<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"tn-301-vs-givinostat\">TN-301 ile Givinostat Kar\u015f\u0131la\u015ft\u0131rmas\u0131<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>TN-301 tedavisi, 3 mg\/kg gibi d\u00fc\u015f\u00fck dozlarda bile kavrama g\u00fcc\u00fcn\u00fc be\u015f hafta i\u00e7inde vah\u015fi tip seviyelerine y\u00fckseltirken, givinostat (klinik maruz kalmalara yak\u0131n 10 mg\/kg) ile tedavi edilen mdx fareleri vah\u015fi tip performans\u0131na ula\u015famad\u0131.<\/strong><\/li>\n\n\n\n<li>TN-301 arac\u0131l\u0131\u011f\u0131yla sa\u011flanan fonksiyonel iyile\u015fmelere, dola\u015f\u0131mdaki kreatin kinaz aktivitesinde azalma ve gen ekspresyonunda olumlu de\u011fi\u015fiklikler e\u015flik etti; bu da kas h\u00fccresi hasar\u0131n\u0131n azald\u0131\u011f\u0131n\u0131 g\u00f6steriyor.<\/li>\n\n\n\n<li><strong>\u0130nsan DMD kaynakl\u0131 pluripotent k\u00f6k h\u00fccrelerden elde edilen kardiyomiyositlerde, TN-301 kalsiyum i\u015fleme anormalliklerini ve mitokondriyal disfonksiyonu d\u00fczeltirken, givinostat DMD kardiyomiyopatisinin bilinen bu etkenlerini daha da k\u00f6t\u00fcle\u015ftirdi.<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Bu olumlu preklinik veriler -ve DMD hastal\u0131k modellerinde HDAC6 inhibit\u00f6rleri kullanan di\u011fer ara\u015ft\u0131rmac\u0131lar\u0131n verileri- topluca, HDAC6 inhibisyonunun, DMD klinik \u00e7al\u0131\u015fmalar\u0131nda pan-HDAC inhibit\u00f6rleriyle bug\u00fcne kadar g\u00f6zlemlenen faydalar\u0131n \u00f6nemli bir b\u00f6l\u00fcm\u00fcn\u00fc olu\u015fturdu\u011funu d\u00fc\u015f\u00fcnd\u00fcrmektedir.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"what-is-tn-301\">TN-301 nedir?<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">TN-301, Tenaya&#039;n\u0131n olduk\u00e7a spesifik k\u00fc\u00e7\u00fck molek\u00fcll\u00fc histon deasetilaz (HDAC) 6 inhibit\u00f6r\u00fcd\u00fcr ve korunmu\u015f ejeksiyon fraksiyonlu kalp yetmezli\u011fi (HFpEF) ve Duchenne kas distrofisi (DMD) tedavisi i\u00e7in umut vadeden preklinik potansiyel g\u00f6stermi\u015ftir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Sa\u011fl\u0131kl\u0131 g\u00f6n\u00fcll\u00fcler \u00fczerinde yap\u0131lan Faz 1 klinik \u00e7al\u0131\u015fmas\u0131nda, TN-301, incelenen geni\u015f doz aral\u0131\u011f\u0131nda genel olarak iyi tolere edildi; doz duyarl\u0131 farmakokinetik \u00f6zelliklere ve g\u00fcnde bir kez dozlamay\u0131 destekleyen bir yar\u0131 \u00f6mre sahipti. \u00d6zellikle, TN-301 ile histon asetilasyonunda herhangi bir de\u011fi\u015fiklik g\u00f6zlenmedi; bu da TN-301&#039;in di\u011fer HDAC&#039;lara k\u0131yasla HDAC6&#039;ya kar\u015f\u0131 3000 kattan fazla se\u00e7icili\u011fini vurgulamakta ve daha az se\u00e7ici HDAC6 veya pan-HDAC inhibisyonunda g\u00f6zlemlenen hedef d\u0131\u015f\u0131 etkilerden ka\u00e7\u0131nma potansiyelini desteklemektedir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">HDAC6 inhibisyonu, \u00e7ok y\u00f6nl\u00fc bir etki mekanizmas\u0131 yoluyla h\u00fccresel s\u00fcre\u00e7leri koordine etmek i\u00e7in sitoskeletal ve di\u011fer proteinleri de\u011fi\u015ftirerek kalp ve v\u00fccuttaki di\u011fer organlar \u00fczerinde fayda sa\u011flar.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Klinik \u00f6ncesi \u00e7al\u0131\u015fmalarda, Tenaya&#039;n\u0131n HDAC6 inhibit\u00f6rlerinin iltihab\u0131, oksidatif stresi, fibrozisi ve metabolik d\u00fczensizli\u011fi azaltt\u0131\u011f\u0131, ayr\u0131ca otofajiyi, protein kalite kontrol\u00fcn\u00fc, mitokondriyal metabolizmay\u0131 ve lipid metabolizmas\u0131n\u0131 iyile\u015ftirdi\u011fi g\u00f6sterilmi\u015ftir. Tenaya, HDAC6 inhibisyonunun aktivitesi ile hastal\u0131\u011f\u0131n patofizyolojisi aras\u0131nda g\u00fc\u00e7l\u00fc bir uyumun oldu\u011fu kalp, metabolik, kas veya akci\u011fer rahats\u0131zl\u0131klar\u0131 olan hastalarda TN-301&#039;i klinik \u00e7al\u0131\u015fmalara ta\u015f\u0131ma f\u0131rsatlar\u0131n\u0131 ara\u015ft\u0131rmaya kararl\u0131d\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Bu Sayfay\u0131 Takip Edin<\/strong>&nbsp;&gt;&gt;&gt;&nbsp;<a href=\"https:\/\/dmdwarrior.com\/tr\/dmd-therapies\/\" target=\"_blank\" rel=\"noreferrer noopener\">Duchenne i\u00e7in T\u00fcm Klinik Ara\u015ft\u0131rmalar<\/a><\/p>","protected":false},"excerpt":{"rendered":"<p>Tenaya Therapeutics presented encouraging preclinical data evaluating TN-301, the company\u2019s highly selective HDAC6 inhibitor, at the Muscular Dystrophy Association\u2019s Clinical &amp; Scientific Conference 2026 (MDA 2026). In in vitro and in vivo models of Duchenne muscular dystrophy (DMD), TN-301 improved muscle performance and corrected key drivers of DMD cardiomyopathy. TN-301 is Tenaya\u2019s potent and highly [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":6710,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[281],"tags":[362,46,47,521,519,520],"class_list":["post-6708","post","type-post","status-publish","format-standard","has-post-thumbnail","category-press-releases","tag-dmd-cardiomyopathy","tag-duvyzat","tag-givinostat","tag-muscle-degeneration","tag-tenaya","tag-tn-301"],"subtitle":"Tenaya, MDA 2026'da se\u00e7ici HDAC6 inhibit\u00f6r\u00fc TN-301 ile ilgili umut verici preklinik veriler sundu. Duchenne kas distrofisi modellerinde, TN-301 kas fonksiyonunu iyile\u015ftirdi ve DMD kardiyomiyopatisinin temel etkenlerini ele ald\u0131.","_links":{"self":[{"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/posts\/6708","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/comments?post=6708"}],"version-history":[{"count":0,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/posts\/6708\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/media\/6710"}],"wp:attachment":[{"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/media?parent=6708"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/categories?post=6708"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/tags?post=6708"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}