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IGF1 as a Potential Treatment for Rett Syndrome: Safety Assessment in Six Rett Patients

DOI: 10.1155/2012/679801

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Rett syndrome (RTT) is a devastating neurodevelopmental disorder that affects one in ten thousand girls and has no cure. The majority of RTT patients display mutations in the gene that codes for the methyl-CpG-binding protein 2 (MeCP2). Clinical observations and neurobiological analysis of mouse models suggest that defects in the expression of MeCP2 protein compromise the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function, such as insulin-like growth factor 1 (IGF1), are good candidates for ameliorating the symptoms of RTT. IGF1 and its active peptide, (1–3) IGF1, cross the blood brain barrier, and (1–3) IGF1 ameliorates the symptoms of RTT in a mouse model of the disease; therefore they are ideal treatments for neurodevelopmental disorders, including RTT. We performed a pilot study to establish whether there are major risks associated with IGF1 administration in RTT patients. Six young girls with classic RTT received IGF1 subcutaneous injections twice a day for six months, and they were regularly monitored by their primary care physicians and by the unit for RTT in Versilia Hospital (Italy). This study shows that there are no risks associated with IGF1 administration. 1. Introduction Rett Syndrome (RTT) is classified with autism among pervasive developmental disorders (DSM IV) and affects mostly girls (1?:?10000). The outcome of the disorder occurs through different clinical stages [1]: the onset corresponds to an interruption of growth and a decrease in the head circumference growth (stage 1) followed by a second stage with autistic features and regression of acquired skills (language, motor abilities, and purposeful use of hands), appearance of seizures, hand stereotypes, alteration in the cardiorespiratory function, and problems with the autonomic system. The third stage is characterized by a reduction of autistic symptoms, appearance of scoliosis and seizures, followed by a late regression (stage 4). There are several pathologies associated with RTT, one of which is breathing difficulties. Respiration is particularly impaired in Rett patients, and poor autonomic control is considered to play a significant role in the sudden death [2]. Respiration in RTT patients consists of periods of breath holding, hyperventilation, central apneas and Valsalva manoeuvres. Julu et al. [3] suggest that the multiple respiratory dysrythymias could be due to brainstem immaturity. In addition, the majority of RTT patients develop seizures [4, 5]. Other symptoms are


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