548
Personalizing New Therapies for CF
However, new therapies to modulate defective CFTR, the basic defect underlying
CF, have started to reach the clinic and several others are in development or in clini-
cal trials. The novelty of these therapies is that, besides targeting the basic defect
underlying CF, they are mutation specifi c. Although a monogenic disease, CF is
infl uenced by a large number of different genes and biological pathways as well as
by environmental factors that are diffi cult to assess. Therefore, every person with
CF is unique and functional assessment of patients’ tissues ex vivo is important for
diagnosis and prediction of severity of this disease and assessment of responses to
drugs for effective treatment (Amaral 2014 ). This is best achieved by a personalized
approach to CF.
Gene Therapy and Pharmacogenomic Approach to CF
CF is prime candidate for gene therapy. Pharmacogenomic approach to CF starts
with genomic analysis of cells and tissues from CF patients that have been corrected
by gene therapy. These serve as end points of successful treatment when studying
new drugs candidates for CF. Bioinformatic tools are used to analyze the data and
identify genes that reveal drug effi cacy. Pharmacogenomic approach may eventually
provide the opportunity to create drugs in a patient in a mutation-specifi c manner.
In 2012, EC approved Vertex Pharmaceuticals’ KALYDECO™ (ivacaftor) tab-
lets for the treatment of CF in patients age 6 years and older who have G551D muta-
tion in their CF gene. It is a CFTR potentiator and is not indicated for use in patients
with CF due to other mutations in the CF gene. It is not effective in patients with CF
with two copies of the F508del mutation (F508del/F508del) in the CF gene.
References
Amaral MD. Novel personalized therapy for cystic fi brosis: treating the basic defect in all patients.
J Intern Med. 2014. doi: 10.1111/joim.12314.
Bianchi DW, Parker RL, Wentworth J, et al. DNA sequencing versus standard prenatal aneuploidy
screening. N Engl J Med. 2014;370:799–808.
De Lellis L, Curia MC, Veschi S, et al. Methods for routine diagnosis of genomic rearrangements:
multiplex PCR-based methods and future perspectives. Expert Rev Mol Diagn. 2008;8:41–52.
Dhami R, Passini MA, Schuchman EH. Identifi cation of novel biomarkers for Niemann-Pick dis-
ease using gene expression analysis of acid sphingomyelinase knockout mice. Mol Ther.
2006;13:556–64.
Goemans NM, Tulinius M, van den Akke JT, et al. Systemic administration of PRO051 in
Duchenne’s muscular dystrophy. NEJM. 2011;364:1513–22.
Greene MF, Phimister EG. Screening for trisomies in circulating DNA. N Engl J Med.
2014;370:874–5.
16 Personalized Management of Genetic Disorders