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Orla Hardiman

I am Assistant Professor of Molecular Psychiatry since September 2014 and coordinator of the third year of BSc in Human Health and Disease since 2013. My lab studies the molecular mechanisms involved in brain function and plasticity in Health and Disease with a particular interest in Growth Factors. During my training I identified Insulin-like growth factor 1 (IGF1) as a candidate treatment for neurodevelopmental disorders (Tropea e al., 2009), and in my lab I continue the exploration of IGF1 function in basic research and clinical studies (Pini et al., 2012; Pini et al., 2014; Pini et al., 2016). I was among the first to identify IGF1 as an effector of brain plasticity with therapeutic potential. For my expertise in neurodevelopmental disorders and IGF1, I have been invited to international conferences (including plenary speaker at the IGF1 conference in Seattle 2018) and to be an editor for special issues of scientific journals. I also have an interest in teaching and Mentoring. I teach “Biology of Neurological and Neuropsychiatric Disorders” and I mentored a total of 4 PhD students (2 completed), 11 MSc students and 15 undergraduate students. I am the organizer of international workshop (Biology of Brain Disorders 2016) and pursue the divulgation of science to students with disadvantaged backgrounds (Trinity Access Program) and general public.

My lab studies the mechanisms of brain plasticity in health and disease and the effects of IGF1. During my first Postdoctoral training in Scuola Normale Superiore I studied the mechanisms of regeneration in adult nervous system (Tropea et al., 2003). We found that the combined action of growth factors and agents affecting the extracellular matrix integrity are synergistic for the regeneration of the nervous system. Also enriched environment contributes to the regeneration of damaged axons. At MIT I studied the molecular mechanisms of brain plasticity and their function in neurodevelopmental disorders. My paper on activity-dependent transcription analysis, reveals that unexpected molecular mechanisms are involved in brain plasticity, and that each forms of activity dependent plasticity elicits different mechanisms (Tropea et al., 2006). During my years at MIT I identified IGF1 as a major agent for promoting development and plasticity in mutants of Autism Spectrum Disorders in particular Rett Syndrome.

The research on IGF1 and Rett syndrome stands out for its clinical relevance. Rett syndrome is a severe disorder that is lacking a treatment. In my studies I show that IGF1- a growth factor used in children with growth impairments- is able to ameliorate the symptoms of the disease in a mouse model of Rett, and therefore has the potential of leading to a treatment of Rett and other neurodevelopmental disorders (Tropea et al., 2009). I partecipated in safety clinical trials which showed no side effects and efficacy of the treatment (Pini et al., 2012), suggesting that IGF1 promises to be a treatment for Rett syndrome and other neurodevelopmental disorders in the next few years. Additional open label clinical studies in Italy suggest that IGF1 treatment ameliorates the symptoms of Rett in treated patients  (Pini et al., 2014, 2016). In addition, I collaborate with Prof. Walter Kaufmann, who lead the IGF1 clinical trials (Phase 2) at Childrens’ Hospital Boston (NCT01777542) to analyze the bllod samples of the patients and identify potential biomarkers which would instruct following trials. My findings on IGF1 produced a new line of research for the use of IGF1 and its derivatives in neuropsychiatric disorders, and the efficacy of IGF1 has been proven for other disorders of the autism spectrum, and two additional clinical studies are currently in place to test IGF1 efficacy in disorders of the autism spectrum (NCT01525901, NCT01970345).

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