tag:blogger.com,1999:blog-7535774120903384819.post694456633481395297..comments2023-12-27T00:26:40.602-08:00Comments on Possibilities: NACFC 2015--Details from Day 1Rebeccahttp://www.blogger.com/profile/01834134399653596127noreply@blogger.comBlogger3125tag:blogger.com,1999:blog-7535774120903384819.post-91215905683377297842015-10-15T02:31:42.102-07:002015-10-15T02:31:42.102-07:00Couple of follow-on notes about the gene therapy t...Couple of follow-on notes about the gene therapy trial <br />in Robb's wake...<br /><br />-- Patients with severe lung disease were *excluded* from the trial because it was assumed that fibrosis etc would prevent the transfer of the gene.<br /><br />-- Patients who showed the *greatest* benefit were the most-severe group admitted... those with 50-70% FEV1 at outset. Their treatment effect was substantial, comfortably out performing Orkambi (for example).<br /><br />-- A less substantial treatment effect was observed in those with a starting 70-90% FEV1. And the most compelling hypothesis put forward for this is that the dose became too diffuse in those with a larger lung capacity / smaller airways open. <br /><br />That is why they are proposing a follow-on study with increased dose - with a higher dose concentration they expect the 70-90% group to show more substantial treatment benefit.<br /><br />Interesting adjunct: the proposed increased dose is safe... but it causes a brief temperature spike, which would have unblinded the study as it is such a tell-tale marker of the Real Thing. The next study will work to remain blinded while accommodating this treatment effect.<br /><br />My view on gene therapy at this stage is that its great merit is being a therapy that works for all mutation sets.<br /><br />The fact that lung decline was halted in the group receiving 'appropriate dose' (per above) is, to me, exciting - that arrested/slowed decline is exactly what we celebrate about Kalydeco for gating mutations.<br /><br />It's also worth noting that a viral vector has now been identified that seems appropriate for use in CF gene therapy and looks set to be vastly more effective as a delivery method that the liposome.Iamtinhttps://www.blogger.com/profile/15716102160475270421noreply@blogger.comtag:blogger.com,1999:blog-7535774120903384819.post-78021109525687893612015-10-10T13:03:30.107-07:002015-10-10T13:03:30.107-07:00I look forward to hearing your CRISPR take, especi...I look forward to hearing your CRISPR take, especially wrt ProQR. I couldn't make it this year.Julie Deschhttps://www.blogger.com/profile/09092038871409572798noreply@blogger.comtag:blogger.com,1999:blog-7535774120903384819.post-24754267624408896192015-10-09T09:52:02.342-07:002015-10-09T09:52:02.342-07:00Quick note: your photo of the slide from the UKGTC...Quick note: your photo of the slide from the UKGTC presentation shows that the cohort with lower lung function showed significant improvement, whereas those with higher lung function did not show significant improvement. They theorize, again, as your slide shows, it's an issue of deposition. That issue would still be there in any non-viral vector that I know of; unclear to me that gene editing would have a mechanism of delivery that could overcome this?Robb St. Lawrencehttps://www.blogger.com/profile/05394279288342898285noreply@blogger.com