Current trends in biobanking for rare diseases: a review
Biospecimens held in biobanks are a valuable resource that allows researchers and clinicians to understand the mechanism and underlying cause of rare disease. Collections of DNA have been used to discover new genes and gene mutations, identify new diagnostic criteria, and genotype–phenotype correlations. On the other hand, sera and plasma have enabled the identification of new biomarkers and protein profiles to identify disease. Other types of biospecimens such as mRNA, cell lines, and tissues have assisted in collecting functional data to identify new pathways and new therapies to be applied to rare diseases. In the future, linking biobanks and registries with other data source will enable clinicians and researchers to gain a better understanding of a disease.
In a recent publication in the Journal of Biorepository Science for Applied Medicine (Current trends in biobanking for rare diseases: a review) RD-Connect, NeurOmics and EURenOmics partners review the current and future direction of rare disease biobanks and discuss the research and development stemming from the use of biospecimens and how this is used to improve management of rare diseases.
The full review and video abstract with commentary from RD-Connect partners Hugh Dawkins and Caroline Graham (Office of Population Health Genomics, Western Australian Department of Health), and Kate Bushby, (Newcastle University) can be found here.
Biomarkers and their use in monitoring disease progression in rare diseases
Biomarkers are particularly important for monitoring disease progression and therapeutic efficacy in rare diseases where cohort sizes are small and clinical phenotypes can be highly variable. Two research groups have published results from proteomic studies in an attempt to identify and validate blood borne biomarkers in patients with muscular dystrophy.
Ayoglu et al (2014) used a multiplexed antibody suspension bead array to perform proteomic profiling of 345 samples collected by the EU-FP7 BIO-NMD consortium partners. Results from this study identified the presence of a number of proteins including carbonic anhydrase III (CA3), myosin light chain 3 (MYL3), malate dehydrogenase 2 (MDH2) and electron transfer flavoprotein A (ETFA) that were present in the blood from DMD patients at a higher level than healthy controls.
In a separate paper by Martin et al (2014), a MS-based bottom-up pipeline approach was used to identify and validate serum biomarkers for the progression of DMD. Results showed a significant increase in Fibronectin levels in patients with DMD when compared to other muscular dystrophies such as Becker muscular dystrophy or Bethlem myopathy. Furthermore, elevated levels were also observed in longitudinal studies in DMD patients over duration of 4 years.
Collectively, the results from these publications suggest protein biomarkers found in blood and serum have the potential to be used as indicators of disease phenotype and severity which make them key candidates for novel diagnostic clinical tests and management of muscular dystrophies.
Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessing SPP1 and LTBP4 variants
Duchenne muscular dystrophy (DMD) is characterised by muscle degeneration with variable progression towards loss of ambulation. Recent studies have suggested such differences in disease progression could be associated with genetic modifiers in the SPP1 and LTBP4 loci. In this paper, van den Bergen et al (2014) present the results from a large multicentre genetic association study of SNPs at the LTBP4 and SPP1 loci in patients with DMD. Results demonstrated a correlation between disease progression and the IAAM haplotype of the LTBP4 gene (rs2303729, rs1131620, rs1051303 and rs10880). However, as opposed to previous studies, no significant correlation between SNP rs28357094 in the SSPP1 gene and disease progression was observed. These results highlight the importance of replicating genetic association studies in order to qualify prognostic biomarkers, and also that future DMD trials should consider the LTBP4 haplotype prior to stratification of patients.
EuroBioBank: 10 year review
Established in 2001 and operational in 2003, the EuroBioBank (EBB) network was established under the European Commission’s 5th framework programme, with the aim of improving accessibility of biospecimens and associated data on rare diseases. The network is made up of 16 partners from 8 European countries (Belgium, France,Germany, Hungary, Italy, Malta, Slovenia and Spain). In this review, Mora et al., 2014 have provided an overview of the past 10 years of EuroBioBank from the start-up and consolidation phases to current partnerships with RD-Connect and BBMRI-ERIC.