{"id":5018,"date":"2017-06-02T10:58:35","date_gmt":"2017-06-02T10:58:35","guid":{"rendered":"https:\/\/laforcedmd.com\/?p=5018\/"},"modified":"2022-05-03T18:21:47","modified_gmt":"2022-05-03T18:21:47","slug":"ataluren-promising-treatment-for-dmd","status":"publish","type":"post","link":"https:\/\/laforcedmd.com\/en\/ataluren-promising-treatment-for-dmd\/","title":{"rendered":"Portrait of Duchenne \u2013 Ataluren a promising treatment for DMD"},"content":{"rendered":"<p><strong>Ellen Welch, PhD<\/strong><\/p>\n<p>Group leader biology at PTC Therapeutics, South Plainfield, New Jersey, USA<\/p>\n<p>&nbsp;<\/p>\n<p><strong>In this fourth interview of our series \u201c<em>Portrait of Duchenne<\/em>\u201d, La Force DMD talks with Ellen Welch<\/strong><strong>,<\/strong><strong> Ph.D., Group leader biology at PTC Therapeutics. <\/strong><strong>She has been working on a treatment for DMD called ataluren (Translarna\u2122). She earned her Ph.D. at the University of Massachusetts Medical School, where she worked on nonsense mutations and how they affect gene expression.\u00a0<\/strong><\/p>\n<p>&nbsp;<\/p>\n<p><strong>Already approved and reimbursed in Europe<\/strong><\/p>\n<p>Ataluren is a treatment for Duchenne muscular dystrophy (DMD) that has been approved for use in Europe and even reimbursed in the UK. It is currently under the FDA review for marketing approval in the USA. Unfortunately, PTC Therapeutics has not filed an application to market ataluren in Canada. We met the PTC Therapeutics team to gather information to understand how exactly this treatment works. New clinical trials are opening for children with DMD. We hope this treatment will be available soon for the Canadian DMD community.<\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p><strong>A treatment for nonsense mutation<\/strong><\/p>\n<p><u><\/u>Ataluren is the first treatment to address an underlying cause of DMD: a nonsense mutation. The nonsense mutation occurs about 13% of the DMD population. As you probably know, DMD is a rare, progressive genetic disorder. Children born with DMD do not produce enough dystrophin<strong>,<\/strong> an important structural component of muscle, causing muscle cells to break down and die. Some cases of DMD are caused by nonsense mutations, which are errors in the genetic code that prematurely stop the production of dystrophin.<\/p>\n<p>Our goal, with this interview, is to help you understand key information about the nonsense mutation and how the treatment works.<\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p><iframe loading=\"lazy\" title=\"Portrait of Duchennne - Ataluren a promising treatment for DMD\" width=\"1140\" height=\"641\" src=\"https:\/\/www.youtube.com\/embed\/UKi0AgYOrM8?start=17&#038;feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture\" allowfullscreen><\/iframe><\/p>\n<p><strong>In the video, Dr. Ellen Welch answers our questions about nonsense mutation and ataluren<\/strong><\/p>\n<p>&nbsp;<\/p>\n<p><strong>What is a nonsense mutation?<\/strong><\/p>\n<p>So I think what you first have to understand is that all the genetic information in the cells is encoded in DNA. You make a copy of DNA into RNA (ribonucleic acid) and then RNA is the template that the cell uses in order to make a protein. So when you have a nonsense mutation in a gene \u2013 so if you took the DMD gene, for instance, and you get a point mutation in DMD \u2013 when that DNA is copied into RNA, that point mutation can now be part of the RNA that becomes what\u2019s called a premature stop codon. So this is what Anakin has: he has a premature stop. So what does that mean? It means when the cell uses this piece of RNA to make a protein, that it cannot make a full-length protein because it has this premature stop signal. It\u2019s got a signal in the cell that says stop making the protein. And that signal is in the wrong place.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>How does ataluren help the production of dystrophin?<\/strong><\/p>\n<p>And what dystrophin does is it links the membrane of the muscle to the inside of the cell \u2013 acts as like a shock absorber \u2013 so when you walk, your muscle cells don\u2019t break open. So when you only have one part of dystrophin, it can\u2019t make that link. So if you can read through the premature stop, now you can trick, what ataluren does, it tricks the cell and says don\u2019t stop there, keep going. And then you can make the full-length protein, so now you can link the inside and the outside of the cell together, and that helps to stabilize the muscle. So what we know from what ataluren does is, when you translate \u2013 encounter the premature stop codon \u2013 the cell machinery is able to insert another amino acid, one of the building blocks for a protein, there. So when it inserts that building block, then it can go on and make the rest of the protein normally. You just have to get through that one hurdle, but that hurdle is a component of the cellular machinery that\u2019s very highly regulated. Because it\u2019s important for the cell, when it really comes to the normal stop signal, to stop. Otherwise, you\u2019ll make these weird proteins and the cell could be very toxic. So, you have to overcome this sort of desire of the cell to stop there. So, ataluren does overcome that. It doesn\u2019t restore it to a wild-type level, but we think it restores it enough to stabilize the disease, and that\u2019s what we\u2019ve shown in our clinical trials to date. So, it just tricks the cell a little bit to make a full-length protein.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>How do you envision the future for people with DMD?<\/strong><\/p>\n<p>I think it\u2019s very optimistic. I think that there are a lot of companies who are making drugs for DMD now. I think there\u2019s ataluren for the read-through population. I think there\u2019s exon skipping that\u2019s coming. Other people are working on things that, other proteins that you can up-regulate to replace dystrophin like utrophin. They\u2019re doing that. So, I think there\u2019s a lot of, there\u2019s a nucleus of people that are basically working from many different directions to identify treatments for DMD. So, I think it\u2019s pretty optimistic, even for kids now. I think it will just get better. But I think I\u2019m fairly optimistic.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Actions to help access to ataluren in Canada<\/strong><\/p>\n<p>There are a couple of things that you can do right now to help us promote access to ataluren in Canada. Here are three actions that you take right now that will help the DMD community:<\/p>\n<p>1- Be aware of your genetic profile. If you don\u2019t have it, ask your doctor.<\/p>\n<p>2- Get in touch with us. E-mail us, follow-us. We\u2019ll be documenting government approval processes<\/p>\n<p>3- Spread the word. Share our content, share pertinent information, and tell your stories.<\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p><strong>Up next:<\/strong><\/p>\n<p>Our next portrait:\u00a0Joanne Donovan, Chief Medical Officer and Senior Vice President, Clinical Development, Catabasis Pharmaceuticals<\/p>\n<p>To receive the next interview in our series \u201c<em>Portrait of Duchenne<\/em>\u201d, please\u00a0<a href=\"\/?page_id=3379\"><strong>subscribe to our newsletter<\/strong><\/a>.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Acknowledgements<\/strong><\/p>\n<p>We thank the PTC Therapeutics team, who received us with open arms to conduct a series of interviews.<\/p>\n<p>We thank Allain Lagadic and Daniel Cooper<\/p>\n<p>&nbsp;<\/p>\n<p><a href=\"http:\/\/www.ptcbio.com\/en\/\" target=\"_blank\" rel=\"noopener noreferrer\">PTC Therapeutics<\/a><\/p>\n<p><a href=\"https:\/\/fr.wikipedia.org\/wiki\/Ataluren\" target=\"_blank\" rel=\"noopener noreferrer\">Ataluren (Translarna\u2122)<\/a><\/p>\n<p><a href=\"http:\/\/ir.ptcbio.com\/releasedetail.cfm?ReleaseID=936905\" target=\"_blank\" rel=\"noopener noreferrer\">ACT DMD Clinical Trial of Translarna\u2122 (ataluren)<\/a><\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Ellen Welch, PhD Group leader biology at PTC Therapeutics, South Plainfield, New Jersey, USA &nbsp; In this fourth interview of our series \u201cPortrait of Duchenne\u201d, La Force DMD talks with Ellen Welch, Ph.D., Group leader biology at PTC Therapeutics. She has been working on a treatment for DMD called ataluren (Translarna\u2122). She earned her Ph.D. [&hellip;]<\/p>\n","protected":false},"author":3,"featured_media":5028,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[18],"tags":[],"class_list":["post-5018","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-treatments"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Portrait of Duchenne \u2013 Ataluren, a promising treatment for DMD<\/title>\n<meta name=\"description\" content=\"Ellen Welch, Group leader biology at PTC Therapeutics. 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