December 29 2009
The BIO-NMD consortium, led by the University of Ferrara’s Dra. Alessandra Ferlini will focus current funding on identifying biomarkers in the Collagen VI myopathies and Duchenne muscular dystrophy. The 3 year project is currently funded through Dec 2012. The study will first evaluate muscle tissue biospecimens available through the EuroBioBank, and then move to evaluate blood and urine specimens for disease specific biomarkers. Preliminary biomarkers identified during the first 18 months, will subsequently be validated in prospective patient cohorts as part of the study.
What is the purpose of the study?
The goal of the study is to find a marker of disease (biomarker) in the blood or urine for UCMD (Ullrich CMD/Bethlem myopathy) and Duchenne muscular dystrophy.
Why is it important to have a disease specific biomarker?
A biomarker is a critical tool to make clinical trials in the CMDs and DMD a reality. A biomarker will allow a clinical trial expert to determine if a drug is having a positive effect on improving disease.
How will a disease specific biomarker provide useful information?
The CMDs can be slowly and variably progressive diseases even within one particular genetic subtype (collagen VI CMD). Clinical trials are expensive. Trials typically run for less than 18 months. It can be difficult to see a “positive” drug effect that produces subtle but important changes on an affected child’s functional abilities. Furthermore, each future enrolled child or adult may have slightly different functional abilities at the beginning of a clinical trial. A biomarker can level the playing field and allow a clinical trial expert to determine how a drug is affecting each child or adult based upon changes in that child’s/adult’s biomarker levels over the course of the trial. Given the limited number of children and adults with a particular neuromuscular disease who can participate in future clinical trials, it is critically important to identify objective changes and increase the sensitivity and power of a study.
How have biomarkers been used in prior neuromuscular clinical trials?
In the current Ataluren trial (PTC Therapeutics) in Duchenne muscular dystrophy, a drug effect was measured by testing enrolled boys’:
- Pulmonary function (outcome measure)
- Ability to walk (outcome measure) using the 6 min Walk Test
- Blood work (no proven Duchenne biomarker)
- Serial punch muscle biopsies (the gold standard biomarker).
BIO-NMD PROJECT ABSTRACT
The rapidly expanding knowledge of NMDs genetic diagnosis, pathogenesis and therapeutic possibilities has provided new targets for disease characterisation, early diagnosis, drug discovery and development as well as has raised many questions about how to translate this knowledge into clinical practice as (initial) clinical trials typically run for such a short time that clinical improvement can hardly be expected within that time frame. This militates for the discovery of surrogate endpoints for establishing the efficacy of clinical trials. The concept of biomarkers represents measurable bio-parameters able to flank the process of diagnosis, functional characterisation and therapy in NMDs.
OMIC sciences (genomic, transcriptomics, proteomics) offer opportunities to identify biomarkers for finely defining and tuning the NMDs bases. This approach can make available non-invasive biomarkers, to be used for monitoring disease progression, prognosis and drugs response, therefore optimising the choice of appropriate and often personalised therapies. Validated biomarkers will increase therapy efficiency (meaning optimal dose of drug to get responders) and efficacy (responders vs non responders for example if we will identify genomic biomarkers linked to the lack of any therapeutic effect). In this case we could address a truly efficacious therapy (avoiding inefficacious treatment due to unfavourable genomic contexts). The new genomic and proteomic biomarkers discovered within BIO-NMD will be validated both in animal models and in human samples, before entering into a qualification process at the EMEA. The qualified biomarkers resulting from the BIO-NMD project will be ready for ongoing and further clinical trials for the patient benefit. This will increase the therapy efficacy and efficiency and also reduce adverse effects, with impact on patients’ quality of life with also economical relevance.
The BIO-NMD consortium is led by the University of Ferrara, an internationally recognised university in the field of genomics of hereditary neuromuscular disorders. In addition the consortium is composed of 7 leading European academic partners bringing their expertise in all OMIC sciences as well as in bio-informatics and patient sample collection, 1 SME providing its skills in bio-informatics and 1 global company specialised in the development of patient samples screening. The BIO-NMD study is funded through a European Union Health Call (FP 7) for 5,700,000 Euros.
