Performance of the GARD assay in a blind Cosmetics Europe study
Johansson H, Gradin R, Forreryd A, Agemark M, Zeller K, Malmborg-Hager A1, Johansson A, Larne O, Van Vliet E3, Borrebaeck C, Lindstedt M,
SenzaGen AB, Lund, Sweden, Department of Immunotechnology, Lund University, Lund, Sweden, Cosmetics Europe –The Personal Care Association, Brussels, Belgium
Introduction
Chemical hypersensitivity is an immunological response to foreign substances. Primarily, these give rise to the clinical symptoms known as allergic contact dermatitis. To mitigate risks associated with consumer products, chemicals are screened for sensitizing effects. Historically, such predictive screenings have been performed using animal models, but industrial and regulatory authorities now demand animal-free methods for the assessment of sensitization. This is a global development spreading across industries and markets. To meet this demand, the Genomic Allergen Rapid Detection (GARD) assay has been developed. Here, we present novel data reconfirming the performance and accuracy of GARD.
Resume
The performance of GARD is highly accurate
83% (72 chemicals)
86% (127 chemicals)
83% (72 chemicals)
Correlated GARD predictions and potency classifications
SenzaGen is presenting at hosted sessions at Society of Toxicology 56th Annual Meeting in Baltimore March 12-16, 2017
Lund University Scientist Andy Forreryd and SenzaGen CEO Anki Malmborg Hager will give a presentatios about the GARD assay at exhibitor hosted sessions at the Society of Toxicology 56th Annual Meeting in Baltimore, on the 13th and 14th of March.
The meeting promises more than 150 scientific sessions, approximately 350 ToxExpo exhibitors offering you the latest information on services and technology, thousands of abstract presentations, continuing education courses, awards presentations, receptions, career guidance and support, and more.
Presentations details
– Replacement of Animal Testing for CLP/GHS Classification of Skin Sensitizers is now possible using a Modified Genomic GARDskin [OECD TGP 4.106] Assay
SenzaGen presents the latest development towards reliable potency classification of chemicals according to CLP 1A and 1B, taking both LLNA and Human potency data in consideration. The assay is based on GARDskin and utilizes a refined gene expression signature developed specifically for potency categorization with high predictability.
Date: 3/13 Time: 13:30 -14:30 Room: 338
– Advantages with Genome Testing Opening up the Landscape for New Application Possibilities for Sensitization Testing using SenzaGen’s Genomic GARD Assay
SenzaGen’s GARD assay is based on expression analysis of predictive genomic biomarker signatures. Prediction calls of test substances are generated by computational methods based on machine learning. SenzaGen presents their experience in skin and respiratory sensitization testing, working with challenging compounds and mixtures, active substances, potency classification and NOEL interpretation.
Date: 3/14 Time: 13:30-14:30 Room: 338
These session are Exhibitor-Hosted Session. Although not an official part of the SOT Annual Meeting scientific program, its presentation is permitted by the Society.
Attendees are welcomed from researcher community, industry, manufacturers, regulatory agencies, consultants, CROs and every one interested in safety testing of chemical compounds.
The GARD™ assay for potency assessment of skin sensitizing chemicals
Kathrin S. Zeller, Andy Forreryd, Tim Lindberg, Ann-Sofie Albrekt, Aakash Chawade, Malin Lindstedt
Dept. of Immunotechnology, Lund University, Lund, Sweden; Swedish University of Agricultural Sciences, Alnarp, Sweden
Summary
The GARD assay is a cell-based transcriptional biomarker assay for the prediction of chemical ensitizers1 targeting key event 3, dendritic cell activation, of the skin sensitization AOP. Here, we present a modified assay based on Random Forest modelling, which is capable of predicting CLP
potency classes (1A – strong sensitizers, 1B – weak sensitizers, no category – non-sensitizers) as described by the European CLP regulation with an accuracy of 75 % (no cat), 75 % (1B) and 88 % (1A) based on a test set consisting of 18 chemicals previously unseen to the model.
We further can link the activation of distinct pathways to the chemical protein reactivity, showing that our transcriptomic approach can reveal information contributing to the understanding of underlying mechanisms in sensitization.
Results and Discussion
We here present a potency prediction approach based on a Random Forest model and 18 transcripts. 18 chemicals previously unseen to the model were classified as shown in Tables 1, 4 and Fig. 1. Interestingly, diethyl maleate, misclassified as 1A instead of 1B, is a human potency class 2 according to4, and iodopropynyl butylcarbamate, wrongly predicted as 1B instead of 1A, is classified as human potency class 44. Thus, the model seems to show more agreement with human data than CLP classifications (mainly derived from animal data) based on this limited dataset. Also Fig. 1C supports the hypothesis, that both data and model contain information allowing the prediction of human potency.
Furthermore, Key Pathway Advisor analysis reveals that these data can be used to investigate the cellular response in more detail (Table 3). In conclusion, we show that the modified GARD assay is capable of providing potency information, which is imperative for quantitative risk assessment of chemical sensitizers.
The GARD assay for potency assessment of skin sensitizing chemicals_ESTIV 2016_Zeller_p
GARD™ – The story
Olivia Larne, Andy Forreryd, Ann Sofie Albrekt, Carl Arne Krister Borrebaeck, Henrik Johansson, Malin Lindstedt
SenzaGen, Sweden, Lund, Department of Immunotechnology, Lund University, Sweden, Lund
Background
To prevent the general population for unnecessary exposure to sensitizing substances, the substances have to be safety tested. Regulatory authorities and economic interests request animal free methodology. Genomic Allergen Rapid Detection, GARD, is an in vitro test developed for the prediction of sensitizing chemicals. It is based on differential expression of disease-associated genomic biomarkers in a human myeloid dendritic cell line.
Here, we describe the development of the GARD platform and its downstream innovations.
Poster:
GARD – The Story_ESTIV 2016
GARD™ – the future of sensitization testing and safety assessment of chemicals using a genomic-based platform
BACKGROUND
Genomic Allergen Rapid Detection, GARD, is an in vitro test developed for the prediction of sensitizing chemicals. It is based on differential expression of disease-associated genomic biomarkers in a human myeloid dendritic cell line.
Here, we describe the development, scientific validation, applications and the current state of the GARD platform. The scientific rationale behind the use of genomic biomarker signatures are detailed, linked to the AOP in a biological context, and to advantages realized through multivariate computational prediction models in a technological context.
RESUME
The GARD assay is elastic, it can be used for several applications. Today, two are developed:
GARDskin
– Hazard identification of skin sensitizers
– Accuracy: ~90%
– Initiated ECVAM validation (OECD TGP no. 4.106)
GARDair
– Hazard identification of respiratory sensitizers
– Accuracy: ~85%
GARD™ – the future of sensitization testing and safety assessment of chemicals, using a genomics-based platform
Henrik Johansson, Andy Forreryd, Olivia Larne, Ann Sofie Albrekt, Carl Arne Krister Borrebaeck, Malin Lindstedt
SenzaGen, Sweden, Lund, Department of Immunotechnology, Lund University, Sweden, Lund
Background
Genomic Allergen Rapid Detection, GARD, is an in vitro test developed for the prediction of sensitizing chemicals. It is based on differential expression of disease-associated genomic biomarkers in a human myeloid dendritic cell line.
Here, we describe the development, scientific validation, applications and the current state of the GARD platform. The scientific rationale behind the use of genomic biomarker signatures are detailed, linked to the AOP in a biological context, and to advantages realized through multivariate computational prediction models in a technological context.
Resume
GARDskin
– Hazard identification of skin sensitizers
– Accuracy: ~90%
– Initiated ECVAM validation (OECD TGP no. 4.106)
GARDair
– Hazard identification of respiratory sensitizers
– Accuracy: ~85%
Anki Malmborg Hager elected one of the two most powerful people among Lund technology companies according to Rapidus ranking
The news site Rapidus has been looking into nealy 180 companies of extended IDEON business park in Lund, Sweden in a unique survey of decision-makers of the region. Ericsson veteran Tord Wingren and Alligator Bioscience co-founder Anki Malmborg-Hager were ranked two of the most powerful people among Lund technology companies.
Rapidus writes:
Leeding up to the expansion of the concept of Ideon, Rapidus went through the records of company boards and chief executives of all technology companies which have their registered office at Ideon Medicon Village, Mobile Heights Center and Edison Park.
In total it ads up to around 700 decision makers of almost 180 companies. Most of them only sit on one board or CEO positions however 56 of these people have posiotions in more than one technology company on the extended Ideon area. At the top of the list are a dozen people with at least three appointments, including the CEO of Jolife Erik von Schenck and Professor Carl Borrebaeck, who among several appointments is on the board of Alligator Bioscience and Clinical Laserthermia Systems.
Read the full news at Rapidus site (only subscribers)
