Project: Regenerating the diabetic heart and kidney by using stress-specific thyroid hormone nanocarriers

Acronym	REASON (Reference Number: EURONANOMED2019-049)
Duration	01/01/2020 - 31/12/2022
Project Topic	Diabetic cardiomyopathy (DC) and diabetic nephropathy (DN) are two major complications of diabetes that account for more than two thirds of deaths in the diabetic population. Primary hallmarks of these conditions are cell dedifferentiation, hypertrophy and maladaptive proliferation through the reactivation of classic developmental pathways. Preclinical and early clinical studies indicated that thyroid hormone (TH) treatment could be a potential strategy for reversing or preventing this maladaptive recapitulation of organ development. However, there is a major obstacle to translating this strategy into clinical practice: the high doses of TH that are needed to induce tissue repair and regeneration may cause several adverse effects. To maximise TH therapeutic efficacy and minimise its adverse effects we aim to develop innovative nanoparticle-based drug delivery systems that will be able to target and deliver L-triiodothyronin (T3) in diabetes-injured cells in order to restore cardiac and renal function and hopefully regenerate damaged tissue. First, using computation models and nanopolymers, we will design and develop smart T3-nanocarriers that will be functionalised for a molecule that can recognise and bind stressed-injured cardiomyocytes and podocytes. In another approach we will use an additional targeting that will confine the drug after injection at a magnetically targeted site. To guarantee efficiency and safety we will fine-tune the properties of the system by analysing data from advanced microscopy and pharmacodynamic studies, and toxicity tests. Finally, we will evaluate the therapeutic efficacy of the system in animal models of DC and DN by analysing integrated genetic, molecular, biochemical, physiological, histological and transcriptome data, and develop a focused dissemination plan to bring the treatment of DC and DN one step closer to clinical translation.
Network	EuroNanoMed III
Call	Joint Transnational Call (2019)

Project partner

Number	Name	Role	Country
1	Istituto di Ricerche Farmacologiche Mario Negri IRCCS	Coordinator	Italy
2	National and Kapodistrian University of Athens	Partner	Greece
3	National and Kapodistrian University of Athens	Partner	Greece
4	University of Sofia	Partner	Bulgaria
5	OZ BIOSCIENCES SAS	Partner	France