Systemic Lupus Erythematosus (SLE) – Biochemical characterisation of subgroups within SLE for improved diagnosis and treatment

acureomics — Tue, 08 May 2012 10:21:23 +0000

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with symptoms ranging from skin related problems to more severe cardiovascular effects. The heterogenous representation of the disease might be the reason for the lack of efficient treatment.In this study, the authors have utilised the Karolinska lupus cohort that consists of 320 SLE patients and 320 age-matched controls. Two main subgroups were defined: One group was defined as having SSA and SSB antibodies and a negative lupus anticoagulant test (LAC), that is, a ‘Sjögren-like’ group. The other group was defi ned as being negative for SSA and SSB
antibodies but positive in the LAC test. According to previous studies these patients are at increased risk for cardiovascular events as compared to the ‘Sjörgren-like’ group. A pilot study was designed and EDTA-plasma from selected patients in these two groups and controls were analysed using a proteomic and metabolomic approach. Pathway analysis was then performed on the obtained data. The pilot study showed that it was possible to differentiate the two subgroups of SLE.
Using our selected biomarkers it will be possible to identify more homogenous patient populations for clinical trials and thereby increase the effi cacy. This combined proteomics-metabolomics approach is likely to identify pathways that may lead to better understanding of the disease, identification of novel drug targets and biomarkers supporting improved diagnosis of SLE.

Reference: http://ard.bmj.com/letters/submit/annrheumdis;71/Suppl_1/A12-b
Helena Idborg,1 Ganna Oliynyk,1 Stefan Rännar,2 Jenny Forshed,3 Rui Mamede Branca,3 Magdalena Donten,2 Johanna Gustafsson,1 Anna Vikerfors,1 Iva Gunnarsson,1 Johan Trygg,4 Janne Lehtiö,3 Torbjörn Lundstedt,5 Elisabet Svenungsson,1 Per-Johan Jakobsson1, SYSTEMS BIOLOGY OF SLE: BIOCHEMICAL CHARACTERISATION OF SUBGROUPS WITHIN SLE FOR IMPROVED DIAGNOSIS AND TREATMENT, Ann Rheum Dis A12 2012;71(Suppl 1):A1–A93

1Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; 2AcureOmics AB, Umeå, Sweden;3Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Science for Life Laboratory and Karolinska Institutet, Stockholm, Sweden; 4Computational Life Science Cluster, Department of Chemistry, Umeå University, Umeå, Sweden; 5Organic Pharmaceutical Chemistry BMC, Uppsala University, Uppsala, Sweden

Diagnostic properties of metabolic perturbations in rheumatoid arthritis

acureomics — Wed, 09 Feb 2011 20:08:42 +0000

This is the first time that the usefulness of metabolic profiling has been demonstrated in the diagnosis of RA.This study assessed the feasibility of diagnosing early rheumatoid arthritis (RA) by metabolic biomarkers. RA patients were diagnosed with a sensitivity of 93% and a specificity of 70% in a validation study using detection of 52 metabolites. Patients with RA or PsoA could be distinguished with a sensitivity of 90% and a specificity of 94%.

We compared the metabolic profile of patients with RA with that of healthy controls and patients with psoriatic arthritis (PsoA). The metabolites were measured using two different chromatography-mass spectrometry platforms, thereby giving a broad overview of serum metabolites. . Glyceric acid, D-ribofuranose and hypoxanthine were increased in RA patients, whereas histidine, threonic acid, methionine, cholesterol, asparagine and threonine were all decreased compared with healthy controls.

It appears that the method can be developed as a complementary diagnostic tool and is one that is especially applicable to patients who are seronegative for ACPA.

Download publication here: DOI: http://arthritis-research.com/content/13/1/R19

Reference: Madsen RK, Lundstedt T, Gabrielsson J, Sennbro CJ, Alenius GM, Moritz T, Rantapää-Dahlqvist S, Trygg J, Diagnostic properties of metabolic perturbations in Rheumatoid Arthritis, ARTHRITIS RESEARCH & THERAPY, 2011, 13:R19

About AcureOmics: Company based in Umeå, Sweden and a leader in metabolomics and metabolic profiling on autoimmune diseases, including rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE) and diabetes (T1D,T2D,MODY). Together with clinicians, biotech companies, patient organizations and universities we develop therapeutic, diagnostic and prognostic biomarkers for more individual-based, personalized healthcare. AcureOmics is also part of BOLD (Biology of Liver and Pancreatic Development and Disease), a Marie Curie Initial Training Network (ITN) within EU’s FP7 program 2009-2013.

Serum metabolite signature predicts the acute onset of diabetes in spontaneously diabetic congenic BB rats

acureomics — Sat, 13 Nov 2010 17:21:32 +0000

The clinical presentation of type 1 diabetes is preceded by a prodrome of beta cell autoimmunity. We probed the short period of subtle metabolic abnormalities, which precede the acute onset of diabetes in the spontaneously diabetic BB rat, by analyzing the serum metabolite profile detected with combined gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS). We found that the metabolitepattern prior to diabetes included 17 metabolites, which differed between individual diabetes prone (DP) BB rats and their age and sex matched diabetes resistant (DR) littermates. As the metabolite signature at the 40 days of age baseline failed to distinguish DP from DR, there was a brief 10-day period after which the diabetes prediction pattern was observed, that includes fatty acids (e.g. oleamide), phospholipids (e.g. phosphocholines) and amino acids (e.g. isoleucine).

It is concluded that distinct changes in the serum metabolite pattern predict type 1 diabetes and precede the appearance of insulitis in spontaneously diabetic BB DP rats. This observation should prove useful to dissect mechanisms of type 1 diabetes.

Download publication here: DOI: http://www.springerlink.com/content/x4073657mq9u1518/

REFERENCE: Åkesson L, Trygg J, Fuller JM, Madsen R, Gabrielsson J, Bruce S, Stenlund H, Tupling T, Pefley R, Lundstedt T, Lernmark Å, Moritz T, Serum metabolite signature predicts the acute onset of diabetes in spontaneously diabetic congenic BB rats, METABOLOMICS, 7(4) 593-603 2011

Press release Nature publication

acureomics — Tue, 10 Aug 2010 15:43:08 +0000

AcureOmics associates participated in a large international project (MAQC-II) aimed to examine and generate ”best practice” protocols in data analysis for predicting clinical endpoints based on gene expression data.

Umeå University researchers Dr Johan Trygg and Dr Max Bylesjö took part in the international sudy coordinated by the United States Food and Drug Administration (FDA). The project is part of FDAs recent ”Critical Path Initiative” to medical product development. The contribution from the Umeå University researchers was in the field of multivariate data analysis technique known as chemometrics and the results have been published in the latest issue of the Nature Biotechnology.

- Understanding the limitations using gene expression data for predicting clinical endpoints is critical for safe and effective development of diagnostic tests and provide a solid foundation also for metabolomics data, says Johan Trygg.
For further information, go to Umeå University website link, http://www.umu.se/english/about-umu/news-events/news/newsdetailpage/umea-researchers-outline-best-practice-in-analysis-of-gene-expression-data-.cid136582

Reference: Leming Shi et al., The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models,
Nature Biotechnology, Aug 09 2010. doi:10.1038/nbt.1665

Published online 30 juli, 2010
http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.1665.html

Renewed SME status for AcureOmics

acureomics — Thu, 15 Apr 2010 15:42:14 +0000

AcureOmics AB has renewed its’ status as SME (micro, small and medium-sized enterprizes) with EMA (European Medicines Agency).
- The SME status is important for AcureOmics AB and has proven to be key for establishing collaborations and gaining access to research networks in the European community, says Jon Gabrielsson, CEO AcureOmics AB.

For further information from the SME Office click here

Metabolomics in functional foods – A powerful complement to randomized clinical trials

acureomics — Wed, 13 Jan 2010 16:36:55 +0000

Functional foods are foods or dietary ingredients that provide a health benefit beyond basic nutrition. A new legislation, known as the Nutrition and Health Claims Regulation, defines the legal framework for such claims within the European Union. Any claim about the nutritional or physiological effects of a product must be scientifically demonstrated. In this study, we have focused on the exploration of metabolomics as a complementary profiling technology to establish monitoring/data analysis procedures of randomized nutritional trials. More specifically, a combined intake of soybean and grapefruit in a human intervention study was analyzed with respect to both pharmacological and physiological effects. Resulting multivariate models showed a diet-induced decrease of lactate, cholesterols and triglycerides. The most drastically elevated metabolite, myo-inositol, was found to accompany a marked reduction of triglyceride levels. Suggestively, this is due to the biotransformation of myo-inositol to phosphatidylinositol, which results in a decrease of available precursors to form triglycerides. Strong inter-subject variation was present that required special attention. Dynamic modelling of collected time series data that provided the opportunity to identify slow, medium or fast responders as well as groups of subjects showing different response profiles, was also highlighted in the study.F

The applied strategy of time series data has proven to be a powerful complement to randomized nutritional studies adopting a clinical trials

Download publication here: DOI: http://10.1016/j.chemolab.2010.07.001

REFERENCE: Lundstedt T, Hedenström M, Soeria-Atmadja D, Hammerling U, Gabrielsson J, Olsson J ,Trygg J, Dynamic modelling of time series data in nutritional metabonomics — A powerful complement to randomized clinical trials in functional food studies, CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS, 104:112-120:2010

Press release: AcureOmics AB granted millions by EU for metabolic disease project

acureomics — Wed, 02 Dec 2009 15:40:26 +0000

AcureOmics is taking part in BOLD (Biology of Liver and Pancreatic Development and Disease), a Marie Curie Initial Training Network (ITN) within EU’s FP7 program. The BOLD project aims to provide new knowledge on metabolic disease of the liver and pancreas. The 4 MEUR project is coordinated by the University of Birmingham and will run through 2013.

AcureOmics will develop tools for routine assessment (“high throughput”) of disease symptoms found in the liver and pancreas, both in animal models and patients with disturbed metabolism. The aim is to develop new treatment for related diseases, based on increased knowledge on individual disturbances in metabolism and the regulation of genetic and metabolic factors will affect the functions. In this way links between individual genotype and metabolic profile can be found that will primarily increase the understanding of development of diabetes BOLD will also generate new tools to assess individuals’ response to treatment depending on genotype and “metabotype”.

AcureOmics, part of Umeå Biotech Incubator (UBI), is based on leading research conducted at Umeå University, the Swedish University of Agricultural Sciences (SLU) and Uppsala University. In close collaboration with clinical researchers and molecular biologists AcureOmics will enhance the possibilities of finding slinks between genotype and changes in the metabolic profile.

- The fact that AcureOmics was selected as partner in an EU network shows that we are leaders in the field. The financing is a significant contribution for the development of our metabolomics research towards sample analysis techniques and will enable us to create a network with leading researchers within the field in Europe, says Jon Gabrielsson, CEO, AcureOmics AB. Jon Gabrielsson also admits that there is already a well working cooperation with several of the researchers at Umeå University and SLU. This has surely contributed to opening doors to EU research. Two researchers, Johan Trygg and Thomas Moritz are also on the board of AcureOmics.,

- Of course it is a great pleasure for us as researchers to have the possibility to develop our research results in order to create benefit for patients, says docent Johan Trygg, senior lecturer at Umeå University, Sweden. Johan Trygg and his research group are also part of the Computational life science cluster (CLiC, www.kbc.umu.se/clic), an interdisciplinary centre in chemometrics and bioinformatics at the university centre for Chemistry and Biology (KBC). He is a pioneer in multivariate data analysis, methods necessary for extracting information from the large and complex data sets that created. Kickoff for the project took place in Birmingham, 28-29 Jan 2010. In total there are 10 partners from eight different European countries that cooperate in the project. AcureOmics AB and the Hungarian company Biotecont are participating as industrial partners, so called SME, but AcurePharma AB from Uppsala and the world’s largest pharmaceutical company Pfizer are also involved in the project.

Metabolomics for monitoring kidney-transplant patients

acureomics — Sat, 04 Jul 2009 19:23:54 +0000

Kidney transplant provides the only hope for a normal life for patients with end-stage renal disease, i.e.,kidney failure. Unfortunately, the lack of available organs leaves some patients on the waiting list for years. In this article, we describe a novel strategy for monitoring kidney transplanted patients for immune responses and adverse drug effects in their early recovery.

The post-transplant treatment is extremely important for the final outcome of the surgery, since immune responses, drug toxicity and other complications pose a real and present threat to the patient. Nineteen patients were followed for two weeks after renal transplantation, two of them experienced problems related to kidney function, both of whom were correctly identified by means of nuclear magnetic resonance spectroscopic analysis of urine samples and multivariate data analysis.

Download publication here: DOI: 10.1016/j.chemolab.2009.04.013

REFERENCE: Stenlund H, Madsen R, Vivi A, Calderisi M, Lundstedt T, Tassini M, Carmellini M, Trygg J, Monitoring kidney-transplant patients using metabolomics and dynamic modeling, CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS, 98: 45-50 2009

Press release: Acureomics associate receives Herman Wold medal in gold

acureomics — Wed, 24 Jun 2009 15:38:42 +0000

AcureOmics cofounder Johan Trygg awarded Herman Wold gold medal Dr Johan Trygg is the youngest ever recipient of the Herman Wold medal in gold, awarded by Swedish Chemical Society to researchers whos contributions have been of great importance for the development of chemometrics. Since 1995 the prize has been exclusively awarded to seven legendary professors in the field.

-The last two years have been really successful for me. Last year I received the Elsevier Chemometrics Award. On top of that I was given one of the career grants that Umeå University commit to young researchers. And now I can add the Herman Wold medal to my resume, says Johan Trygg, university lecturer at Umeå University and chairman of AcureOmics.

Dr Trygg received his gold medal at a ceremony held during the Scandinavian Symposium on Chemometrics (http://org.uib.no/ssc11/) conference in Loen, Norway, June 8-11 2009.

For further information in Swedish from Umeå University website, click here.

About AcureOmics
AcureOmics AB is devoted to personalized medicine, systems biology including the ”omics” fields of research and the areas of biofluid profiling. Services are provided in analysis of collected samples using NMR, MS and/or other techniques needed as well as multivariate data analysis of the complex data structures that result from such studies. AcureOmics is a company with unique competence in the ”omics” field of data analysis and interpretation.

Download press release

AcureOmics asscociates keynote speakers at SSC11

acureomics — Wed, 13 May 2009 15:34:44 +0000

AcureOmics founders speak at SSC11

Professor Torbjörn Lundstedt and associate professor Johan Trygg, two of the founders of AcureOmics AB, are invited lecturers at the 11^th Scandinavian Symposium on Chemometrics (SSC11). The SSC conferences are biannual and rotate amongst the Nordic countries, this year taking place in Loen/Stryn, Norway. Johan Trygg opened the conference with a presentation on the role of chemometrics in personalized medicine. In Torbjörn Lundstedts lecture he shared his experience on chemometric strategies for extracting holistic information. The conference is held between June 8-11, for more information click here.