Abstract
Rett syndrome (RTT) is a devastating neurodevelopmental disorder that has no cure. Patients show regression of acquired skills, motor, and speech impairment, cardio-respiratory distress, microcephaly, and stereotyped hand movements. The majority of RTT patients display mutations in the gene that codes for the Methyl-CpG binding protein 2 (MeCP2), which is involved in the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function are good candidates for ameliorating the symptoms of RTT. In particular, insulin-like growth factor 1 (IGF1) and its active peptide (1–3) IGF1 cross the Blood Brain Barrier, and therefore are ideal treatments for RTT Indeed, both (1–3) IGF1 and IGF1 treatment significantly ameliorates RTT symptoms in a mouse model of the disease In a previous study, we established that IGF1 is safe and well tolerated on Rett patients. In this open label clinical case study, we assess the safety and tolerability of IGF1 administration in two cycles of the treatment. Before and after each cycle, we monitored the clinical and blood parameters, autonomic function, and social and cognitive abilities, and we found that IGF1 was well tolerated each time and did not induce any side effect, nor it interfered with the other treatments that the patient was undergoing. We noticed a moderate improvement in the cognitive, social, and autonomic abilities of the patient after each cycle but the benefits were not retained between the two cycles, consistent with the pre-clinical observation that treatments for RTT should be administered through life. We find that repeated IGF1 treatment is safe and well tolerated in Rett patients but observed effects are not retained between cycles. These results have applications to other pathologies considering that IGF1 has been shown to be effective in other disorders of the autism spectrum.
Highlights
The clinical case study performed in this experiment depicts the efficacy and safety of insulin-like growth factor 1 (IGF1) exposure upon two cycles of treatment
Considering the finding that any treatment for Rett syndrome (RTT) should be administered for life [8], our research addresses the issue of multiple IGF1 treatments and tolerability in children with RTT syndrome
During our first study [12], we observed the major improvements during the first weeks of IGF1 treatment, and for this reason, we decided to reduce the time of the second treatment to 20 weeks
Summary
The clinical case study performed in this experiment depicts the efficacy and safety of insulin-like growth factor 1 (IGF1) exposure upon two cycles of treatment. The second round of treatment started on the 20th of November 2012 and discontinued on the 28th of February 2013. The effects of MECP2 mutations lead to a loss of function or overexpression of the MeCP2 protein. If it results in a loss of function state, some examples of effects yield: classic RTT, atypical RTT, autism, and mild mental retardation [2]. The majority of RTT patients (85%) have mutations in the MECP2 gene that lead to loss of MECP2 protein function. At this point of time, there is no cure to RTT syndrome, treatment strategies are starting to emerge
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