We hypothesize that inappropriate thyroid hormone action in target cells is a common mechanism underlying susceptibility to age-related degenerative diseases and co-morbidities. Although regulation of systemic thyroid status is well understood and underpins treatment of common thyroid disease, it is only in the last decade that the importance of local regulation of thyroid hormone action in tissue development, homeostasis and repair has been identified. During evolution, this complex temporal and cell-specific regulation has been optimized for development and reproductive fitness but NOT for ageing. Humans with their exceptional longevity are thus exposed to a prolonged period of suboptimal local thyroid hormone action. Consistent with this, thyroid status is a continuous variable within the population that is related to fracture risk, muscle mass and cognitive decline. Moreover, in healthy longevity thyroid status is characterized by thyroid stimulating hormone in the upper half of the reference range. In these studies, we will determine how local regulation of thyroid hormone action controls tissue homeostasis and repair, whilst its dysregulation is a common mechanism underlying chronic disease development during ageing. We focus on osteoporosis, osteoarthritis, neurodegeneration and sarcopenia as paradigm age-related, degenerative disorders. Using cutting-edge technology, we will (i) identify thyroid hormone dependent biomarkers for disease susceptibility in bone, cartilage, central nervous system and skeletal muscle, (ii) manipulate cell-specific thyroid hormone action in these tissues and (iii) develop cell-type specific modulators of thyroid hormone action. THYRAGE integrates cross-disciplinary expertise from clinical and basic scientists, endocrinologists, neuroscientists, gerontologists, and industry-based peptide scientists. These studies will identify and validate novel strategies for prevention and treatment of chronic age-related degenerative disease.

ReWIRE will combine innovative translational neurotechnologies and rehabilitation interventions for the repair and restoration of neurological functions following injury of the spinal cord (SC). The proposed research program will equip next-generation scientists with unique skills to develop disruptive therapeutic solutions for patients with paralysis. Recent technological breakthroughs have triggered a paradigm shift in the conception of therapies aimed to restore function after spinal cord injury (SCI). Novel drug delivery systems and biomaterial bridges have been engineered to reduce secondary injury and scarring, to stimulate and guide regenerating nerve fibres across the lesion site, and to promote functional reconnection with intact tissue. Additionally, neuromodulation therapies can reactivate spinal circuits below a SCI, allowing people with chronic paralysis to regain voluntary control of walking. In conjunction with rehabilitation, neurological recovery was promoted that persisted without neuromodulation, suggesting a rewiring of the SC as demonstrated in preclinical models. To bypass an injury, neuromodulation has been linked to brain signals to re-establish cortical control over spinal circuits by employing electrical nerve stimulation and robotic systems. Advances in robotics are significantly augmenting the impact of neurorehabilitation by inducing new natural “wired” connections. The aim of ReWIRE is to leverage all these technical and therapeutic breakthroughs in the framework of multiple PhD projects that will continuously interact to converge toward effective combinatorial treatments for SCI. ReWIRE will focus on three inter-woven objectives: i) establish an international, interdisciplinary, and intersectoral educational network, ii) build an SCI clinical data platform, and, iii) position Europe at the forefront of therapy for SCI.