Investigating the Mechanism of Action of a Disease-Modifying Treatment for Parkinson’s Disease Using Bulk and Spatial Transcriptomics

Herantis Pharma is a Finnish company that develops disease-modifying therapies for neurodegenerative diseases, with a focus on Parkinson’s disease. Genevia Technologies provides bioinformatics support for the preclinical mechanism-of-action studies of their lead molecule. We interviewed the Chief Scientific Officer of Herantis Pharma, Dr. Henri Huttunen, about their work and collaboration with Genevia Technologies.

Background

Herantis Pharma is a clinical-stage biotechnology company developing a disease-modifying therapy for Parkinson’s disease. Current treatments for this neurodegenerative disease only alleviate symptoms and gradually lose effectiveness as the disease progresses. Herantis Pharma’s lead molecule, HER-096, aims to stop or even reverse neuron degeneration by mimicking the neurotrophic factor CDNF.

In addition to clinical trials, Herantis Pharma conducts extensive preclinical research on the mechanisms of action of HER-096, which is closely linked to their biomarker discovery efforts. Different omics experiments are used to examine the highly complex and multifaceted biology behind the disease and effects of HER-096. Previously, the omics-related projects were straightforward enough for Herantis’s scientists to handle data analysis internally, but as the datasets grew larger and the bioinformatics and systems biology questions became more complex, they ran out of internal resources.

– As a small company, we are very used to a working model in which many tasks are outsourced, so it was quite natural for us to seek external help for bioinformatics as well, says Dr. Huttunen.

Dr. Huttunen’s first contact with Genevia Technologies had occurred years ago when Herantis’s work was still focused on clinical programs that did not require bioinformatics support. The situation changed in 2023, prompting the need for support with bulk transcriptomics data, and especially, spatial transcriptomic data from the Nanostring GeoMx platform. Dr. Huttunen reached out to Genevia to explore how they could assist.

Exploring Data with Genevia Technologies

Since September 2023, the Genevia team has been analyzing transcriptomic data from Herantis’s preclinical disease models to better understand the pathology and treatment effects of HER-096 at the cellular level. Dr. Huttunen describes the collaboration:

– We are using both bulk and spatial transcriptomics to look at changes in different cell types in the tissue after treatment. When we started working with Genevia, we spent some time looking for the best technical approach. We began with bulk transcriptomics, and then moved on to GeoMx spatial transcriptomics. The technology was new to us, and at that point, we were not even sure about our exact research questions. We started exploring the data together, trying to find the direction we wanted to go, and I think that was exactly what we needed. We have all learned a lot in the process, and Genevia’s support has been excellent.

The Herantis team has been working with Genevia’s Scientific Project Manager, Dr. Joana Viana. Dr. Huttunen believes that Dr. Viana’s background in neurobiology makes her perfectly suited for the project, and says that his team appreciates particularly her communication skills and the way results are reported.

– She is able to explain the technical side very well to us non-bioinformaticians and has been very patient with our questions. This is very important in this kind of interface where we understand the biology and she has the bioinformatics and methodological knowledge. There has to be an overlap for the project to result in something useful, Dr. Huttunen explains.

– In our first meetings, Joana presented the results in slideshows, and we discussed the topics in more general terms. Later, she created an HTML-based system that makes it easy for us to dive back into the analyses. There is so much data and so many nuances that it takes a lot of time to understand everything, so this format for reporting has been extraordinarily helpful. It keeps the complex data sets well organized and makes it easy to go back if we come up with new questions later on.

Dr. Huttunen notes that Herantis Pharma’s working model has been semi-virtual for about 15 years, making Genevia's service model, the Virtual Bioinformatics Core, a good match for them. He praises the flexibility and efficiency of the 0.25 FTE arrangement used for their collaboration.

– We don’t have any labs or production lines, for example. In practice, we are a core team of about 10 people, and a huge network of collaborators. So, we have seen a wide spectrum of what can go right and wrong with these kinds of collaborations. Based on this experience, I would, without a doubt, recommend Genevia – this collaboration has been just easy and great in many ways, he says.

The cooperation continues, and Dr. Huttunen is optimistic about the upcoming phases of the project.

– For the GeoMx project, new samples are being sequenced, so soon we will be able to dive into a batch of data from a different time point. Overall, we are hoping to gain some mechanistically actionable insights; the kind of questions and answers that we would then be able to start validating with other experiments, to test certain biomarkers, for example. The first round was very intriguing, and I believe that this second round will reveal an even clearer picture, Dr. Huttunen concludes.

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