The NP at my clinic asked if I could help find articles for a patient with a rare gating mutation, that would support the patient's insurance appeal for Kalydeco off-label.
I found the following 2 articles and sent her the following message highlighting the most helpful parts of the articles:
The first one, ' A little CFTR goes a long way', while not related to the mutation the patient has, concludes with the thrilling words, "In sum, the corrected in vivo estimates of restored CFTR function overlap estimates based on patch clamp data,and suggest that excellent clinical responses can be expected by restoring less than 10% of CFTR function." Therefore if the patient's mutation is in the same class as the ones that showed improvement, is is likely to also be improved by ivacaftor as even a small improvement in functional CFTR results in excellent clinical responses.
The second article, Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Ivacaftor Therapy in the Context of CFTR Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Ivacaftor Therapy in the Context of CFTR Genotype states:
"Ultimately, it was discovered that for ivacaftor to be effective, two conditions must be present in the epithelium.
First, CFTR must be expressed on the cell surface, meaning that mutations associated with improper folding or improper trafficking of protein to the cell surface are not ameliorated by ivacaftor. Second, the expressed protein must be capable of activation via normal intracellular signaling mechanisms, in particular, cyclic adenosine monophosphate/protein kinase A pathways including β-adrenergic or adenosine receptor stimulation."
So if you could show the mutation has these 2 properties, that could be evidence favoring trial use of ivacaftor.
I tried uploading these 2 articles but they exceed the server size limit of this web site. Please PM me if you would like copies. Alternately, these are available free online so you could just google them.
I found the following 2 articles and sent her the following message highlighting the most helpful parts of the articles:
The first one, ' A little CFTR goes a long way', while not related to the mutation the patient has, concludes with the thrilling words, "In sum, the corrected in vivo estimates of restored CFTR function overlap estimates based on patch clamp data,and suggest that excellent clinical responses can be expected by restoring less than 10% of CFTR function." Therefore if the patient's mutation is in the same class as the ones that showed improvement, is is likely to also be improved by ivacaftor as even a small improvement in functional CFTR results in excellent clinical responses.
The second article, Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Ivacaftor Therapy in the Context of CFTR Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Ivacaftor Therapy in the Context of CFTR Genotype states:
"Ultimately, it was discovered that for ivacaftor to be effective, two conditions must be present in the epithelium.
First, CFTR must be expressed on the cell surface, meaning that mutations associated with improper folding or improper trafficking of protein to the cell surface are not ameliorated by ivacaftor. Second, the expressed protein must be capable of activation via normal intracellular signaling mechanisms, in particular, cyclic adenosine monophosphate/protein kinase A pathways including β-adrenergic or adenosine receptor stimulation."
So if you could show the mutation has these 2 properties, that could be evidence favoring trial use of ivacaftor.
I tried uploading these 2 articles but they exceed the server size limit of this web site. Please PM me if you would like copies. Alternately, these are available free online so you could just google them.