Guest guest Posted March 4, 2004 Report Share Posted March 4, 2004 Sara, That is also Eilish's mutation so I would love to hear any information you get about it. (Australia) Re: Gentamicin I discussed this with Zach's doctor since Zach has a stop mutation (K710X). His theory was that gentamicin would be altered in such a way that it would no long be an " antibiotic " , but it would still be able to correct the CFTR malfunction in stop mutations. How this might be accomplished is anyone's guess. He also theorized that if one mutation could be corrected then the person might only have the CFTR malfunction of a carrier. In France they are testing ways to turn on the sodium chloride channel in the G551D mutation. That is Zach's other mutation so I am very interested in that too. Sara > > I read that in testing Gentamicin in nasal applications it can result > > in read-through of CTFR protein for people with Grade I mutations > > (ex. G542, W1282X, R553X, 1717-1G->A) > > > > http://content.nejm.org/cgi/content/short/349/15/1433 > > > > I think this drug is usually used for urinary infections. Has anyone > > ever heard of it being used for CF? ------------------------------------------- The opinions and information exchanged on this list should IN NO WAY be construed as medical advice. PLEASE CONSULT YOUR PHYSICIAN BEFORE CHANGING ANY MEDICATIONS OR TREATMENTS. ------------------------------------ _____ Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 4, 2004 Report Share Posted March 4, 2004 This is a pubmed article I found. It is very difficult to understand but I think the last sentence means that the new drug they were testing restored the CFTR function for G551D. Others might be able to interpret this better. - Sara Comparative pharmacology of the activity of wild-type and G551D mutated CFTR chloride channel: effect of the benzimidazolone derivative NS004. Derand R, Bulteau-Pignoux L, Becq F. Laboratoire des Biomembranes et Signalisation Cellulaire, UMR 6558 CNRS, Universite de Poitiers, 86022 Poitiers, France. The pharmacological activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel mutated at glycine 551 (G551D-CFTR) was studied in the presence of the benzimidazolone derivative NS004 and compared to that of wild-type (wt) CFTR. Using iodide ((125)I) efflux and whole-cell patch-clamp techniques we found dose-dependent stimulation of phosphorylated wt-CFTR channels by NS004 with an EC(50) approximately 11 microM. With non- phosphorylated CFTR, the effect of NS004 was apparent only at concentration >100 microM. In G551D-CFTR-expressing CHO cells, neither forskolin (from 0.1 to 10 microM) nor NS004 (from 0.1 to 200 microM) added separately were able to stimulate channel activity. However, in the presence of 10 microM forskolin, NS004 stimulated G551D-CFTR activity in a dose-dependent manner with an EC(50) approximately 1.5 microM. We also determined the half-maximal effective concentration of forskolin ( EC(50) approximately 3.2 microM) required to stimulate G551D channel activity in presence of 1.5 micro M NS004. No inhibitory effect was observed at high concentration of NS004 with both wt- and G551D-CFTR. Whole-cell recordings of CFTR chloride currents from cells expressing wild-type or G551D-CFTR in the presence of NS004 were linear, time- and voltage-independent. The inhibitory profile of G551D-CFTR channel activity was similar to that of wild type, i.e., inhibition by glibenclamide (100 microM) and DPC (250 microM) but not by DIDS (200 microM) nor calixarene (100 nM). These results show that NS004 activates wt-CFTR channel and restores G551D-CFTR channel activity, the potency of which depends on both the concentration of NS004 and the phosphorylation status of CFTR. > Sara, > > That is also Eilish's mutation so I would love to hear any information > you get about it. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 4, 2004 Report Share Posted March 4, 2004 This is one of 's as well. jan > This is a pubmed article I found. It is very difficult to > understand but I think the last sentence means that the new drug > they were testing restored the CFTR function for G551D. Others > might be able to interpret this better. - Sara Quote Link to comment Share on other sites More sharing options...
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