European gene therapy research may restore essential human senses
A world without hearing, sight or smell; without music, the light of the day or the scent of a delicious meal. This is the reality for those who suffer from congenital cilia diseases, a condition stemming from genetic defects; they go through life missing one or more senses.
Cilia -Latin for eyelashes- are microscopic "hair" structures which grow from the retina, inner ear, nose, kidney and lungs. Their abnormal growth can cause disorders leading to the loss of the basis senses. Sadly, not only can ciliopathies (genetic defects linked to cilia) damage the neurosensory systems, but they can also result in severe syndromic disorders, including diabetes, brain defects and chronic kidney disease.
To research the function of cilia, and its dysfunction, is the primary aim of SYSCILIA – a biological project that is part of the Health Theme of the EU's Seventh Framework Programme (FP7). The project, jointly coordinated by Dr. Ronald Roepman from Radboud University Medical Centre in Nijmegen (The Netherlands) and Professor Marius Ueffing, from Eberhard Karls University's Medical Center in Tübingen (Germany), has been running since 2010 and is due to continue until 2015; the European Union (EU) is contributing just over €11 million in funding.
The project consists of a network of 18 different international teams at various centres. Altogether, participants are operating at 16 universities across six EU countries and the United States. "Without cross-border European co-operation and funding, we would never be able to achieve our goals", says Professor Marius Ueffing.
SYSCILIA's new approach is based on advanced mathematical modelling of biological systems, and includes: comprehensive dataset generation — and a lot of computation; medical genetics and clinical medicine; pharmacology; molecular and cell biology. Based on biochemical and biological data obtained within and outside the project, SYSCILIA research team uses computational models to predict the architecture of protein networks and model the dynamic behaviour of biological pathways within ciliated cells and tissues.
"One big problem in the field is genetic heterogeneity and clinical diversity. As such, conventional approaches, such as classical human genetic or classical pharmacological approaches, fall short when searching for improved diagnostics and novel therapy," says Professor Ueffing. "SYSCILIA, the way we see it, uses systems modelling and network analysis methods developed or applied by us to acquire knowledge on the overarching principles of systems failure in these diseases. This knowledge we want to turn into clinical applications," he adds.
A group of researchers funded from the SYSCILIA project have already discovered a way to restore the sense of smell in mice. Under their direction, rodents born without a sense of smell due to a mutation underwent a new form of gene therapy. The researchers created a virus capable of infecting cells with a working version of the affected gene. This was then injected into the rodents' noses on three consecutive days, restoring the defected cilia — and their sense of smell.
Other ciliary diseases, such as the blinding disorder called LCA5 affecting children, are being investigated together with colleagues from the United States in view of establishing a gene-therapy. "The systems modelling and network analysis tools and knowledge generated in SYSCILIA is now a major asset for our research programme towards a gene therapy for LCA5," says Doctor Ronald Roepman.
Although the SYSCILIA project continues, the achievements so far are encouraging. The new gene therapy approach could be crucial for future research into ciliopathies and prove beneficial not only for mice but very soon for humans, too. What about: "We are reaching out to the pharmaceutical industry, yet have no formal partnership. Furthermore, we have applied for additional EU funding through a Research Training Network, where about 50% of all partners involved come from industry. This proposal -called SYSTRAIL- is currently under evaluation," says Professor Ueffing.
Project acronym: SYSCILIA
Participants: The Netherlands (Coordinator), United Kingdom, Germany, France, Ireland, Italy, United States
Project N° 241955
Total costs: € 14 939 311
EU contribution: € 11 069 083
Duration: June 2010 to May 2015
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