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21 August 2019 / Our Stories

Exploring the human genome through collaborative research

Grünenthal is working with 23andMe – the world’s leading personal genetics company – to explore the potential of genetic data to deepen our understanding of pain, and to enable the development of lifechanging new treatments for patients.

“As thought leader, we strive to find novel therapeutic interventions based on deep disease understanding.”

Achim Kless,

Translational Scientist, Grünenthal

When scientists announced that the Human Genome Project was complete in April 2003, the world celebrated a game-changing moment for life sciences. Today we know that this breakthrough has opened a door to develop lifechanging new treatments. Candidates with genetical validation have a 50% higher chance to pass successfully through development and eventually reach the market1 . But we also need to admit that although we know the genome’s sequence by now, we have little understanding of the respective functionality of around 95% of it. Still, the remaining 5% offer us about 20,000 proteins and another 20,000 non-coding RNA elements – 40,000 potential research targets. To explore the genetic influences on pain, Grünenthal is collaborating with 23andMe, the world’s leading personal genetics company.

Assembling the puzzle

The joint project is one of the largest studies of its kind, involving more than 38,000 genotyped volunteers who have shared their genetic data and medical history. This makes it possible to focus on the genetic profiles of patients with specific indications – which supports Grünenthal in gaining a deeper disease understanding for specific conditions. In the course of the study, the volunteers provided information about their experiences of pain through online surveys and also self-administered the Cold Pressor Test to determine their tolerance for pain. Scientists from Grünenthal and 23andMe then reviewed the data from the surveys and tolerance tests and combined them with the participants’ genetic information.

Genetic factors matter

Designed to increase our disease understanding, enable better stratification of patients, identify biomarkers and investigate genetic predispositions of non-responders, the collaborative research project has delivered some exciting results. For example, the teams have identified promising targets and pathways, as well as frequent comorbidities for certain pain indications. The latter suggests that these indications might be caused by the same genetic factors. Genes that are found to be associated with one or several indications will be further evaluated to support more effective assessments of potential research targets. On top of this, the study has discovered a group of patients whose genetic profile causes them to have fewer receptors, which explains why they are non-responders, not experiencing pain relief from some opioid analgesics. Altogether, the findings of this study could make it possible to develop more personalised treatments that reflect each patients’ unique genetic composition – and enable lifechanging approaches to open a pathway to a world free of pain.
Currently, the teams are finalising the project which runs until the end of the year. While the project has already informed Grünenthal’s pain pathway map, the team is preparing publications to share their findings with the scientific community and our colleagues are indeed already working on a follow-up project that would enable us to explore an even larger gene database.

1 Nelson et al., Nature Genetics (2015) 47, 856

 

“We strive to develop drugs in a much more targeted way using genetics, proteomics and next generation sequencing methods.”

Jan Adams,

acting CSO, Grünenthal

 

Human Genome Project
The Human Genome Project (HGP) was one of the world’s largest international research projects. It aimed to determine the sequence of nucleotide base pairs that make up human DNA, and to identify and map all of the genes of the human genome from both a physical and a functional standpoint. The project formally launched in 1990 and was declared complete on 14 April 2003.

Cold Pressor Test
The cold pressor test is performed by immersing the hand into an ice water container, requiring a participant to hold it there for as long as they can. The two essential data points revealed by the test are the moment when pain is initially felt and the moment when it becomes unbearable, i.e. when the participant removes his/her hand. This provides a measure of pain threshold (first feeling pain) and pain tolerance (total time minus threshold).

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