5476MWT. Several candidates designed to skip other exons and address additional
mutation groups are currently in preclinical development. However, given the
increasingly lower prevalence of mutations, a nonstandard, orphan drug-tailored
design of clinical studies is required. This is supported by the encouraging data
obtained to date with drisapersen and eteplirsen, and may be based on extrapolation
between patient populations, placebo groups and compounds (within a chemical
class). A phase I/IIa study was done to assess the safety, pharmacokinetics, and
molecular and clinical effects of systemically administered drisapersen and results
showed dose-dependent molecular effi cacy in DMD patients with a modest
improvement in the 6-min walk test after 12 weeks of extended treatment (Goemans
et al. 2011 ). Phase III clinical trials in progress. Such approaches, combined with
the ongoing development of new validated endpoints and surrogate biomarkers for
DMD, should bring personalized therapy closer for an increasing number of patients
(van Deutekom et al. 2013 ).
Personalized Treatment of Cystic Fibrosis
Cystic fi brosis (CF) is the most common serious genetic disease among Caucasians
in the US. Although a multi-organ disease, CF is usually diagnosed by symptoms of
pulmonary infections and mucus plugging of the airways, which result from dys-
function of the CF transmembrane conductance regulator (CFTR), an ion channel
that mediates anion transport across epithelia. Defi nite diagnosis of CF requires
proof of CFTR dysfunction, by ‘sweat Cl- test’.
More than 10 million Americans are carriers for CF, including 1 in 25 Caucasians.
Carrier screening can help physicians identify children with CF earlier in life,
allowing parents and medical professionals to begin medical and nutritional inter-
vention that can improve the child’s growth and development, and reduce the inci-
dence of respiratory infections. Over 1,000 mutations and DNA sequence variations
have been identifi ed in the CFTR gene. The F508 mutation is represented in almost
all populations. Carrier testing for CF is aimed at identifying individuals who do not
show signs of the disease, but who carry a genetic mutation that can be passed onto
their offspring. CF is a potentially lethal disease although the current life expec-
tancy has improved to about 30 years with advances in the medical treatment.
Current Management of CF
Currently used methods for the treatment of pulmonary complications of CF include
physiotherapy, bronchodilator therapy, mucolytic agents and corticosteroids. Many
drugs, including mucolytics and antibiotics, aim to alleviate the pulmonary symp-
toms of CF, but do not address the cause of the disease. Lung transplant is the last
resort for advanced pathology. Many of these therapies are individualized according
to the needs of the patients, which vary considerably.
Personalized Treatment of Cystic Fibrosis