Marina Romoli Onlus Association sponsors a collaboration between two US universities
The Marina Romoli Onlus Association (MROA) is sponsoring a collaborative research project between Case Western Reserve University (CWRU) and The Ohio State University (OSU). The total contribution has been of $50.000.
The title of the project is: “Promoting functional reorganization in the injured spinal cord using a combinatorial strategy to maximize recovery”.
The Research will be supervised by Prof. Jerry Silver, principal investigator for CWRU and Dr. Andrea Tedeschi, principal investigator for OSU.This research project, if successful, will bring us much closer to finding therapies to reverse both acute and Chronic Spinal Cord Injury. For more details about the research project see the abstract below.
MROA wants to thank all the supporters, in particular the association named “RIIM” that made a contribution to MROA to fund half project.
“It is an honor for MROA to sponsor a collaboration between these two very prestigious US Universities and we wish the best of luck to both Prof. Silver and Dr. Tedeschi!” Marina Romoli – President of Marina Romoli Onlus Association
About Marina Romoli Onlus Association:
The Marina Romoli Onlus Association was created in 2011 when the professional cyclist Maria Romoli became paraplegic after she was hit by a car during a training session. The association has the goal to support medical research to find a cure for chronic spinal cord injury and to provide financial support to athletes that become disabled practicing sport activities, in particular to the ones who become paralyzed due to spinal cord injury.
Problem: Injuries to the spinal cord disrupt ascending as well as several descending axonal tracts, ultimately leading to both sensory and motor impairment.
Target: Promoting functional reorganization in the injured spinal cord using a combinatorial strategy to maximize recovery.
Goal: Assessing the therapeutic efficacy of combining intracellular sigma peptide with Pregabalin. Injuries to the adult mammalian central nervous system (CNS) cause devastating long-term sensory, motor and cognitive disabilities due to limited sprouting and axon regeneration failure. No therapeutic strategy that restores function is currently available for individuals that have suffered damage to their spinal cords. Over the last few decades, a considerable amount of research has been devoted to investigating the cellular and molecular mechanisms controlling axon growth and regeneration failure. A number of studies have demonstrated that the presence of a non- permissive environment and the poor intrinsic growth potential of most CNS neurons accounts for regeneration failure and lack of functional recovery in the adult. One intriguing hypothesis that helps explain regeneration failure especially at chronic time points after injury is that the tips of severed axons (so-called dystrophic endballs) form synaptic-like connections with glial precursor cells within the lesion penumbra which entraps them indefinitely (Filous et al., 2014). We will need to release this ”brake” and overcome other extrinsic and intrinsic barriers simultaneously in order to maximize any potential for functional regeneration. Thus, one single strategy is unlikely to fully repair the damaged CNS. Spatial and temporal arrangement of neuronal extrinsic and intrinsic mechanisms is crucial for the development of strategies aimed at creating more favorable conditions for functional recovery.
By decreasing interaction with CSPG-rich substrates, one of the major extrinsic barriers to regeneration, administration of a membrane-permeable peptide (Intracellular Sigma Peptide: ISP) that binds and inactivates protein tyrosine phosphatase σ (PTPσ) has allowed substantial recovery in rats after severe spinal cord contusion injury (Lang et al., 2015). Extensive sprouting of serotonergic fibers below the site of injury correlated with functional recovery in these animals (Lang et al., 2015). In vitro studies showed that ISP also has a dramatic effect on adult sensory neurons, which resulted in their ability to regenerate past a potently inhibitory CSPG barrier. However, the effect of ISP on sensory axon regeneration in vivo after SCI has not yet been investigated. Pregabalin (PGB), a potent gabapentinoid commonly used to treat neuropathic pain after SCI, has been recently shown to promote robust regeneration of ascending sensory axons in adult mice after SCI by blocking Alpha2delta2, a neuronal receptor and critical component of the intrinsic molecular “brake” of axon growth and regeneration (Tedeschi et al., 2016).
The goal of the proposed study is to assess the potential for strong therapeutic synergy by combining intracellular sigma peptide with Pregabalin to maximize structural and functional reorganization in acute but especially chronic experimental models of SCI. If successful, this study may have significant impact on the design of clinical interventions aimed at promoting neurological recovery in SCI individuals.
The results of the research project have been published in the following paper: “Gabapentinoid treatment promotes corticospinal plasticity and regeneration following murine spinal cord injury” .
Unfortunately, gabapentinoid treatment shown efficacy just in acute spinal cord injury and did not show synergistic effect with ISP, so the project was terminated.