Spermidine in hypertension: therapeutic potential and novel mechanisms

Project Information

SPeR-ToNE

Grant agreement ID: 101025118

DOI

10.3030/101025118

Project terminated on 31 December 2023

EC signature date 22 February 2021

Start date 21 February 2022

End date 11 June 2025

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 196 707,84

EU contribution

€ 196 707,84

Coordinated by

INSTITUT GUSTAVE ROUSSY
France

Periodic Reporting for period 1 - SPeR-ToNE (Spermidine in hypertension: therapeutic potential and novel mechanisms)

Reporting period: 2022-02-21 to 2024-02-20

Summary of the context and overall objectives of the project

Hypertension remains a leading risk factor for cardiovascular disease, posing major challenges to society and healthcare systems, as only one-third of patients effectively control their blood pressure with existing medications. Toward this end, growing evidence suggests that spermidine, a naturally occurring activator of the cellular housekeeping process, known as autophagy, is associated with lower blood pressure in humans. The project's major objective is to leverage this insight to examine whether spermidine, available as a dietary supplement, can be used to improve blood pressure and, if so, what the underlying mechanisms are.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In preliminary work, spermidine feeding to salt-sensitive hypertensive rats effectively attenuated high blood pressure. To evaluate the mechanisms, particularly autophagy, a mouse model with reduced autophagic capacity was generated. Subsequently, these mice and their wild-type controls were subjected to an experimental protocol of hypertension. However, this model, involving the use of a high-salt diet, failed to induce a sufficient rise in blood pressure, precluding the possibility of evaluating the crosstalk between autophagy, hypertension, and spermidine. Thus, the protocol needs to be modified, or other models need to be used to determine the role of autophagy in the blood pressure-lowering effect of spermidine, which went beyond the budget and timeframe of this project.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Spermidine supplementation is currently undergoing testing for its blood pressure-lowering effects in an ongoing clinical trial involving hypertensive patients. If patients demonstrate similar benefits to those observed in experimental models of the disease, this might lead to the launch of a new class of antihypertensive medications based on autophagy induction, paving the way for changes in patient treatment protocols. In fact, introducing a pluripotent compound, which not only counteracts hypertension but also slows aging at a systemic level, will have a significant impact on medicine as well as the economy. This could reduce the massive bill caused by hypertension, which is expected to continuously increase as lifespan extends, and our aging population grows.

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