{"id":8838,"date":"2026-10-03T11:28:47","date_gmt":"2026-10-03T08:28:47","guid":{"rendered":"https:\/\/dmdwarrior.com\/?p=8838"},"modified":"2026-10-03T12:06:54","modified_gmt":"2026-10-03T09:06:54","slug":"wms-2026-entr-601-44-exon-44-skipping","status":"publish","type":"post","link":"https:\/\/dmdwarrior.com\/tr\/wms-2026-entr-601-44-exon-44-skipping\/","title":{"rendered":"Entrada Therapeutics\u2019in ENTR-601-44 Aday\u0131, Erken D\u00f6nem PK\/PD Verilerinde Doza Ba\u011fl\u0131 Ekzon 44 Atlama Etkisi G\u00f6sterdi"},"content":{"rendered":"<p class=\"wp-block-paragraph\"><strong>Entrada Therapeutics ENTR-601-44, Duchenne kas distrofisi (DMD) hastalar\u0131nda, mutasyonlar\u0131 ekzon 44 atlamas\u0131na uygun olan hastalar i\u00e7in tasarlanm\u0131\u015f, deneysel bir tedavi y\u00f6ntemidir.<\/strong> Japonya'n\u0131n Hiro\u015fima kentinde d\u00fczenlenen D\u00fcnya Kas Toplulu\u011fu'nun 31. Y\u0131ll\u0131k Kongresi'nde sunulan yeni veriler, ENTR-601-44'nin v\u00fccutta nas\u0131l davrand\u0131\u011f\u0131n\u0131 ve maruz kalman\u0131n ekzon 44 atlamas\u0131yla nas\u0131l ili\u015fkili oldu\u011funu inceledi.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">ENTR-601-44 nedir?<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>ENTR-601-44, bir Endozomal Ka\u00e7\u0131\u015f Arac\u0131-fosforodiamidat morfolino oligomer (EEV-PMO) konjugat\u0131d\u0131r.<\/strong> Bu, PMO&#039;nun kas h\u00fccrelerine iletimini iyile\u015ftirmek ve nihayetinde distrofin \u00f6n-haberci RNA&#039;y\u0131 hedef ald\u0131\u011f\u0131 \u00e7ekirde\u011fe ula\u015fmas\u0131n\u0131 sa\u011flamak \u00fczere tasarlanm\u0131\u015ft\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Bu tedavi, ekzon 44'\u00fcn atlanmas\u0131na neden olarak, neredeyse tam uzunlukta ve potansiyel olarak i\u015flevsel bir distrofin proteininin \u00fcretilmesini sa\u011flamay\u0131 ama\u00e7lamaktad\u0131r.<\/strong> Daha \u00f6nceki klinik d\u0131\u015f\u0131 \u00e7al\u0131\u015fmalar, hasta kaynakl\u0131 h\u00fccrelerde ekzon 44 atlanmas\u0131n\u0131, DMD fare modelinde distrofin \u00fcretiminin artmas\u0131n\u0131 ve insan d\u0131\u015f\u0131 primatlarda ekzon 44 atlanmas\u0131n\u0131 g\u00f6stermi\u015ftir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">WMS 2026 posteri, \u00f6zellikle insan d\u0131\u015f\u0131 primatlardan, sa\u011fl\u0131kl\u0131 yeti\u015fkin g\u00f6n\u00fcll\u00fclerden ve ekzon 44 atlamas\u0131na yatk\u0131n DMD'li pediatrik kat\u0131l\u0131mc\u0131lardan elde edilen farmakokinetik ve farmakodinamik verilere odaklanm\u0131\u015ft\u0131r. <strong>Daha fazla bilgi edin<\/strong>:&nbsp;<a href=\"https:\/\/dmdwarrior.com\/tr\/mutations-and-deletions-amenable-to-exon-44-skipping-therapies-dmd\/\" target=\"_blank\" rel=\"noopener\">Ekzon 44 Atlama Terapilerine Uygun Mutasyonlar ve Delesyonlar<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\">ENTR-601-44 Maruziyeti Dozla Birlikte Artt\u0131<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Veriler, hem insan d\u0131\u015f\u0131 primatlarda hem de sa\u011fl\u0131kl\u0131 g\u00f6n\u00fcll\u00fclerde ENTR-601-44&#039;ye plazma maruziyetinin doz artt\u0131k\u00e7a artt\u0131\u011f\u0131n\u0131 g\u00f6sterdi.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>V\u00fccut a\u011f\u0131rl\u0131\u011f\u0131na g\u00f6re ayarlanm\u0131\u015f benzer dozlarda, yeti\u015fkin sa\u011fl\u0131kl\u0131 g\u00f6n\u00fcll\u00fclerdeki maruziyetin, yeti\u015fkin insan d\u0131\u015f\u0131 primatlardakine g\u00f6re yakla\u015f\u0131k iki ila \u00fc\u00e7 kat daha y\u00fcksek oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr.<\/strong> DMD&#039;li kat\u0131l\u0131mc\u0131larda tekrarlanan dozlama, plazmada ENTR-601-44 birikimine dair herhangi bir kan\u0131t g\u00f6stermedi.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u0130lac\u0131n kendisi plazmadan nispeten h\u0131zl\u0131 bir \u015fekilde temizlendi ve bildirilen yar\u0131 \u00f6mr\u00fc yakla\u015f\u0131k 2-4 saatti. Bununla birlikte, son PMO i\u00e7eren metabolit plazmada \u00e7ok daha uzun s\u00fcre kald\u0131 ve yar\u0131 \u00f6mr\u00fc 100 saati a\u015ft\u0131.<\/strong><\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Pediatrik ve Yeti\u015fkin Kat\u0131l\u0131mc\u0131lar Aras\u0131ndaki Farklar<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Poster ayr\u0131ca, 6 mg\/kg dozun uygulanmas\u0131n\u0131n ard\u0131ndan DMD&#039;li \u00e7ocuk kat\u0131l\u0131mc\u0131lar ile sa\u011fl\u0131kl\u0131 yeti\u015fkin g\u00f6n\u00fcll\u00fcler aras\u0131nda g\u00f6r\u00fclen farkl\u0131l\u0131klar\u0131 da ortaya koymu\u015ftur.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Pediatrik kat\u0131l\u0131mc\u0131larda, ilac\u0131n plazmadaki maksimum konsantrasyonu sa\u011fl\u0131kl\u0131 yeti\u015fkin g\u00f6n\u00fcll\u00fclere k\u0131yasla yakla\u015f\u0131k y\u00fczde 43 daha d\u00fc\u015f\u00fckken; zaman i\u00e7indeki toplam ila\u00e7 maruziyetini yans\u0131tan konsantrasyon-zaman e\u011frisi alt\u0131ndaki alan yakla\u015f\u0131k y\u00fczde 58 daha d\u00fc\u015f\u00fckt\u00fc.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Benzer farkl\u0131l\u0131klar, insan d\u0131\u015f\u0131 primatlar \u00fczerinde yap\u0131lan \u00e7al\u0131\u015fmalarda da gen\u00e7 ve yeti\u015fkin hayvanlar aras\u0131nda g\u00f6zlemlenmi\u015ftir.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">ENTR-601-44 \u0130skelet Kas\u0131na Ula\u015ft\u0131<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">En \u00f6nemli bulgulardan biri, iskelet kas\u0131nda son PMO i\u00e7eren metabolitin saptanmas\u0131yd\u0131.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Hem sa\u011fl\u0131kl\u0131 g\u00f6n\u00fcll\u00fclerde hem de insan d\u0131\u015f\u0131 primatlarda doza ba\u011fl\u0131 konsantrasyonlar g\u00f6zlemlendi. <strong>Kar\u015f\u0131la\u015ft\u0131r\u0131labilir dozlarda, kas dokusuna maruz kalma oran\u0131n\u0131n sa\u011fl\u0131kl\u0131 g\u00f6n\u00fcll\u00fclerde insan d\u0131\u015f\u0131 primatlara g\u00f6re yakla\u015f\u0131k \u00fc\u00e7 kat daha y\u00fcksek oldu\u011fu g\u00f6r\u00fcld\u00fc.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Daha da \u00f6nemlisi, DMD&#039;li kat\u0131l\u0131mc\u0131larda, son PMO i\u00e7eren metabolit, \u00fc\u00e7\u00fcnc\u00fc dozdan alt\u0131 hafta sonra bile kas dokusunda hala tespit edilebiliyordu.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Metabolit, hem sa\u011fl\u0131kl\u0131 g\u00f6n\u00fcll\u00fclerde hem de insan d\u0131\u015f\u0131 primatlarda idrarda tespit edildi. 6 mg\/kg dozunda, sa\u011fl\u0131kl\u0131 g\u00f6n\u00fcll\u00fclerde veya DMD&#039;li kat\u0131l\u0131mc\u0131larda b\u00f6brek fonksiyonuyla ilgili klinik olarak anlaml\u0131 bir bulgu bildirilmedi. <strong>Daha fazla bilgi edin<\/strong>: <a href=\"https:\/\/dmdwarrior.com\/tr\/upcoming-exon-44-skipping-therapies-for-dmd\/\" target=\"_blank\" rel=\"noreferrer noopener\">DMD Tedavisine Y\u00f6nelik Yakla\u015fan Ekzon 44 Atlama Tedavileri<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Daha Y\u00fcksek Maruziyet, Daha Fazla Ekzon Atlamas\u0131na Yol A\u00e7abilir<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Gen\u00e7 insan d\u0131\u015f\u0131 primatlarda, ENTR-601-44 maruziyetinin artmas\u0131yla ekzon 44 atlamas\u0131 da artt\u0131. Art\u0131\u015f do\u011frusal de\u011fildi ve \u00f6zellikle test edilen en y\u00fcksek dozda belirgin bir etki g\u00f6zlemlendi.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Bu bulgulara dayanarak, ara\u015ft\u0131rmac\u0131lar, devam eden ELEVATE-44-201 \u00e7al\u0131\u015fmas\u0131n\u0131n sonraki kohortlar\u0131nda 12 mg\/kg veya daha y\u00fcksek dozlarla beklenen daha y\u00fcksek maruziyetlerin potansiyel olarak daha b\u00fcy\u00fck farmakodinamik etkilere yol a\u00e7abilece\u011fini \u00f6ne s\u00fcr\u00fcyorlar.<\/strong><\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Veriler Ne G\u00f6steriyor?<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">WMS 2026 posteri, ENTR-601-44&#039;nin doza ba\u011f\u0131ml\u0131 maruziyete neden oldu\u011funu, iskelet kas\u0131na ula\u015ft\u0131\u011f\u0131n\u0131 ve kaslarda uzun s\u00fcre kalabilen PMO i\u00e7eren bir metabolit \u00fcretti\u011fini g\u00f6steren erken farmakokinetik ve farmakodinamik kan\u0131tlar sunmaktad\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Veriler ayr\u0131ca \u00e7ocuk ve yeti\u015fkin kat\u0131l\u0131mc\u0131lar aras\u0131nda farkl\u0131l\u0131klar oldu\u011funu g\u00f6stermekte ve gen\u00e7 insan d\u0131\u015f\u0131 primatlarda daha y\u00fcksek maruz kalma d\u00fczeylerinde daha g\u00fc\u00e7l\u00fc bir ekzon atlama etkisi oldu\u011funu d\u00fc\u015f\u00fcnd\u00fcrmektedir. <strong>Devam eden Faz 1\/2b ELEVATE-44-201 \u00e7al\u0131\u015fmas\u0131, y\u00fcksek doz gruplar\u0131 da dahil olmak \u00fczere, ekzon 44 atlamas\u0131na yatk\u0131n DMD hastalar\u0131nda ENTR-601-44'yi de\u011ferlendirmektedir.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Daha da \u00f6nemlisi, bu sonu\u00e7lar erken d\u00f6nem PK\/PD bulgular\u0131d\u0131r.<\/strong> Poster, klinik fonksiyonel fayda sa\u011flad\u0131\u011f\u0131na dair kan\u0131t sunmamakta veya ENTR-601-44&#039;nin DMD ilerlemesini yava\u015flatt\u0131\u011f\u0131n\u0131 ortaya koymamaktad\u0131r. Poster, a\u00e7\u0131klanan klinik \u00e7al\u0131\u015fmalarda bug\u00fcne kadar ciddi yan etkiler veya b\u00f6brek fonksiyonunda klinik olarak anlaml\u0131 de\u011fi\u015fiklikler g\u00f6zlemlenmedi\u011fini bildirmektedir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Daha Fazlas\u0131n\u0131 Ke\u015ffedin<\/strong>:&nbsp;<a href=\"https:\/\/dmdwarrior.com\/clinical-trials\/map\/\" target=\"_blank\" rel=\"noopener\">Duchenne Klinik Ara\u015ft\u0131rma Yerleri Haritas\u0131<\/a><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>","protected":false},"excerpt":{"rendered":"<p>Entrada Therapeutics\u2019 ENTR-601-44 is an investigational therapy designed for patients with Duchenne muscular dystrophy (DMD) whose mutations are amenable to exon 44 skipping. New data presented at the 31st Annual Congress of the World Muscle Society in Hiroshima, Japan, examined how ENTR-601-44 behaves in the body and how its exposure relates to exon 44 skipping. [&hellip;]<\/p>\n","protected":false},"author":7,"featured_media":8840,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[281],"tags":[235,265,234,141,127,246,923],"class_list":["post-8838","post","type-post","status-publish","format-standard","has-post-thumbnail","category-press-releases","tag-elevate-44-201","tag-entr-601-44","tag-entrada-therapeutics","tag-exon-44","tag-exon-44-skipping","tag-exon-44-skipping-therapies","tag-wms-2026"],"subtitle":"WMS 2026'da Entrada Therapeutics, DMD'de ekzon 44 atlama terapisine ili\u015fkin yeni ENTR-601-44 verilerini sundu. Bulgular, doza ba\u011fl\u0131 ila\u00e7 maruziyetini, kas i\u00e7i da\u011f\u0131l\u0131m\u0131 ve daha y\u00fcksek dozlarda artan ekzon atlamas\u0131n\u0131 g\u00f6stermektedir.","_links":{"self":[{"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/posts\/8838","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\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/comments?post=8838"}],"version-history":[{"count":2,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/posts\/8838\/revisions"}],"predecessor-version":[{"id":8842,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/posts\/8838\/revisions\/8842"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/media\/8840"}],"wp:attachment":[{"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/media?parent=8838"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/categories?post=8838"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/tags?post=8838"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}