Development and commercialization of a kit for profiling enzyme activity in liquid biopsies

Informations projet

PTMActKit

N° de convention de subvention: 101069334

DOI

10.3030/101069334

Projet clôturé

Date de signature de la CE 19 Mai 2022

Date de début 1 Juillet 2022

Date de fin 31 Decembre 2023

Financé au titre de

• European Research Council (ERC)

Coût total

Aucune donnée

Contribution de l’UE

€ 150 000,00

Coordonné par

WEIZMANN INSTITUTE OF SCIENCE
Israel

Periodic Reporting for period 1 - PTMActKit (Development and commercialization of a kit for profiling enzyme activity in liquid biopsies)

Période du rapport: 2022-07-01 au 2023-12-31

Résumé du contexte et des objectifs généraux du projet

Post-translational modifications (PTMs) of proteins are crucial for controlling proteins' function, binding, stability, etc'. While PTMs are critical determinants in assessing aberration in protein functions, harnessing PTM states into the clinical setting and biomarker discovery has been lagging, mainly due to a lack of technologies to examine alterations in PTMs in a high-throughput manner.

The proposed PoC idea is focused on utilizing the PTM profiling system we had developed to elucidate central questions of ubiquitin-dependent regulation in cancer. We established the proficiency to profile enzymatic activities in different types of clinical samples such as solid tumors, serum, and cerebral-spinal fluid, using PTM profiling. Using the PTMKit proposal we harnessed this technology, to identify novel markers of neuroinflammation, from clinical samples of cerebral spinal fluids. This work will continue to establish a novel way of identifying functional biomarkers in the context of different human diseases and to develop it further for commercial prototypes including
an automated analysis pipeline. We aim to transform proteomics-based precision medicine capabilities, which
will bear a transformative impact on both the clinical and research communities.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

We have managed to characterize the PTM profile, specifically of ubiquitin and ISG15, in cerebral spinal fluids of different pathologies in the central nervous system (CNS). There is a great unmet need for putative biomarkers in neuroinflammation and therefore we decided to pursue this path which would have high commercialization potential. By examining patients' samples, extracted by spinal tapping, we collected 28 samples to be analyzed. Importantly, these samples were collected before diagnosis and therefore reflect an early disease stage. We collected samples from patients who were then diagnosed with Alzheimer's disease, Multiple Sclerosis, Relapsing-remitting, Glioblastoma, and Non-CNS conditions. We identified differential biomarkers across different diseases and others that were shared between all the neuroinflammatory states and were distinct from the non-CNS controls. For one of these biomarkers, we performed validation experiments, using an independent method, to confirm the results. We further continued to calibrate the relevant reagents to be able to scale the detection of said biomarker and also understand its potential role in neurodegeneration. Beyond the unmet need to identify novel biomarkers for neuroinflammatory conditions, the pathway we discovered may offer novel targets for therapeutic intervention.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

In our work, we identified novel biomarkers for neuroinflammation, which present an enormous unmet need today. We are following up on the biomarker we identified to examine its potential across several human indications and different cohorts with different genetic /ethnic backgrounds. Although we did not anticipate it, the target we identified affords novel ways to modulate neuroinflammation and we are examining its potential as a novel target for prevention or delaying the onset of neuroinflammation. We intend to allocate additional funding to substantiate our findings, further develop the kit, and also test the relevance in pre-clinical model systems.

An example of a functional biomarker in AD