Tailored bioinformatics support for a clinical trial

Amazentis is a life science company with roots at the Swiss Federal Institute of Technology (EPFL) in Lausanne, Switzerland, developing a new generation of functional nutrition products backed by solid science. For over ten years, Amazentis has been studying the naturally derived postbiotic, Urolithin A, and its role in fighting age-related muscle decline and promoting healthy aging. Their proprietary Urolithin A formulation (Mitopure®) was tested in multiple clinical studies and showed strong evidence to improve muscle function.

To further investigate molecular mechanisms underlying Mitopure’s function in human skeletal muscle, Amazentis collaborated with Genevia Technologies who provided support through omics analyses. The results of this study showed that Mitopure had a significant impact on biomarkers associated with improved mitochondrial function and mitophagy in human skeletal muscle.

In this interview, we discuss with Dr. Davide D’Amico, R&D Group Leader at Amazentis. His research focused on molecular mechanisms of muscle aging and new interventions to counteract it. He has a special focus on mitochondrial function and mitophagy, the process of recycling and renewing faulty mitochondria. Mitochondrial function and mitophagy decline with aging, resulting in detrimental consequence on many tissues, including the mitochondria-rich skeletal muscle. Here’s how he describes the background of their work:

The lead compound we have developed is a postbiotic called Urolithin A. It’s naturally derived from precursor molecules called ellagitannins, polyphenols that are present in different foods like pomegranates, red berries, and nuts. When you eat these foods, the polyphenols are metabolized by your gut microbiome, generating Urolithin A.

However, not all the people who eat the precursor molecules are able to make the conversion to Urolithin A – this happens in only about 30% of the population and depends on the variability of our gut microflora. To overcome this problem, Amazentis developed a proprietary formulation of Urolithin A, called Mitopure. Mitopure is available through Timeline Nutrition, the consumer health brand of Amazentis.

A decade of research proved that Mitopure administration improves the health of mitochondria, the power generators of our cells. Mitopure has been shown to improve mitophagy in several experimental models.

The beneficial effects of Mitopure have now been translated into humans, through rigorous double-blind, placebo controlled, randomized clinical studies. Results have been published in two high-impact scientific journals, Cell Reports Medicine, and JAMA Network Open.

In the first study, Mitopure was administered for four months to middle-aged, overweight individuals. Functional tests at the end of the studies showed that Mitopure significantly improved muscle strength in these healthy subjects, specifically a 10% increase in the isokinetic hamstring muscle strength.

Achieving this significant improvement in muscle function in just four months in people who are not exercising is a remarkable result.

Next, we looked at the underlying biology. We collected muscle biopsy samples and ran several omics measurements. At this stage, we wanted a top data science company to support us in the analysis. Here is how our collaboration with Genevia started, says Dr. D’Amico.

The results from the omics analyses were striking:

– We had astonishing results from the muscle proteomics dataset, showing that Mitopure administration significantly increased proteins associated with better mitochondrial function and enhanced mitophagy. These pathways were on the top of the list. Increasing mitochondrial health was the most important biological change by Urolithin A in human muscle, based on unbiased analysis. We were really excited to translate our findings from preclinical models into positive evidence in humans.

Collaboration, not a black box

Amazentis had some experience in data analysis, however, the team decided to get support from an external service provider.

– We wanted a third party that could independently analyze the data and present the results in an unbiased manner. We also didn't want to have a black box, but rather a transparent and validated pipeline for our study, Dr. D’Amico explains.

As a lucky coincidence, Amazentis came across the Genevia team at an event aiming to establish a network between companies and academic labs.

– We decided not to join the network at that time, but that’s where we first got in touch with Genevia Technologies. When we realized the amount and critical importance of the omics data to be analyzed, we decided to ask Genevia.

– We really like the flexibility of Genevia’s approach. They go beyond being a simple service provider to give a scientific input that is comparable to a top academic collaboration. In this kind of analysis, there is a need for constant feedback between the company and the service provider. Genevia efficiently manages to maintain this dynamic communication, tailor the analysis to our needs, and keep a very rigorous analytical pipeline.

The collaboration between Amazentis and Genevia continues, and Dr. D’Amico doesn’t hesitate when asked if he would recommend Genevia Technologies to a colleague: – “I definitely would, for both companies and academic labs looking for a top data science company to support their bioinformatic analyses.”

Published research from this collaboration

• Singh, A. et al. (2022). Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell reports. Medicine, 3(5), 100633. https://doi.org/10.1016/j.xcrm.2022.100633
• D’Amico, D. et al. (2023). Topical application of Urolithin A slows intrinsic skin aging and protects from UVB-mediated photodamage: Findings from Randomized Clinical Trials. medRxiv 2023.06.16.23291378. https://doi.org/10.1101/2023.06.16.23291378
• Liu, S. et al. (2023). Urolithin A induces cardioprotection and enhanced mitochondrial quality during natural aging and heart failure. bioRxiv 2023.08.22.55437. https://doi.org/10.1101/2023.08.22.554375