The Marina Romoli Onlus Association is proud to announce that it has donated € 170,000.00 to Imperial College London. Principal Investigator: Simone Di Giovanni, Imperial College London
For more details about the research projects see the abstract below.
Project 1: Pharmacological activation of CBP/p300 for repair and recovery in experimental chronic severe spinal cord injury. (30.000,00 £).
Goal: Combinatorial use of a small molecule activator of CBP with environmental enrichment to enhance axonal regeneration and functional recovery in chronic and severe transection of the spinal cord
Spinal cord injury leads to severe neurological disability and lack of significant functional recovery. Current therapies are limited to neurorehabilitation and neuromodulation and fail to promote significant recovery of function in most patients. Functional recovery depends upon several factors including an enhancement of axonal and synaptic plasticity of spared as well as injured fibers, which also need to sprout and/or regenerate to form new connections.
There is therefore the need to boost the neuroplasticity and regenerative neuronal ability above a critical threshold that will allow maximal efficacy in functional recovery when combined with neurorehabilitation. Additionally, therapeutic approaches in chronic spinal cord injury patients are rarely investigated and remain a high unmet need for the large population of patients currently affected by SCI. Therefore this need has to be met urgently in pre-clinical models of severe and chronic spinal injuries to provide the necessary evidence to support future trials in patients.
Project 2: IDENTIFICATION OF FIBER TRACT-SPECIFIC CELLULAR MICRODOMAINS AFTER ACUTE AND CHRONIC SPINAL CORD INJURY. (140.000,00 £ founded by Marina Romoli Onlus & RIIM).
Goal: Molecular mapping of the acute and chronic spinal cord injury
Abstract: Axonal regenerative failure following spinal cord injury (SCI) is the most critical limitation to the re-connectivity of the disrupted circuitry and to restoration of function. These axonal tracts collapse and retract immediately following an injury and fail to grow back indefinitely posing an insurmountable obstacle to repair in all patients affected by SCI. An unfavorable spinal cord environment mediated by oligodendrocyte, astrocyte, pericyte and immune-dependent mechanisms has been shown to promote axonal retraction and restrict axonal regrowth after SCI. However, therapeutic strategies aimed at antagonizing these inhibitory mechanisms have so far led to only limited success in promoting axonal regeneration. To overcome this limitation, this proposal aims to leverage the recent development of spatial single cell transcriptomics in chronic SCI toinvestigate molecular and cellular signatures that define the spinal cellular microenvironment in proximity to sensory and motor neuronal tracts A spinal thoracic spinal cord transection will be performed in mice and following tracing of sensory and motor neurons, spatial transcriptomics will be performed at 4, 6 and 8 weeks after SCI. These initial critical studies will reveal the cellular identity in axonal tract-specific cellular microdomainsallowing for testing their relevance for axonal regrowth, synaptic plasticity as well as recovery of the sensory and motor systems after SCI.