Rett Syndrome: Treatment with IGF-I, Melatonin, Blackcurrant Extracts, and Rehabilitation

Abstract

Abstract:(1) This study describes the good evolution of a 6-year-old girl genetically diagnosed (R106X) with Rett syndrome (RTT), after having been treated with IGF-I, melatonin (MT), blackcurrant extracts (BC) and rehabilitated for 6 months. (2) The patient stopped normal development in the first year of age. The patient showed short stature and weight and fulfilled the main criteria for typical RTT. Despite her young age, there was pubic hair (Tanner II), very high plasma testosterone, and low levels of plasma gonadotrophins. There were no adrenal enzymatic deficits, and abdominal ultrasound studies were normal. The treatment consisted of IGF-I (0.04 mg/kg/day, 5 days/week, subcutaneous (sc)) for 3 months and then 15 days of rest, MT (50 mg/day, orally, without interruption) and neurorehabilitation. A new blood test, after 3 months of treatment, was absolutely normal and the pubic hair disappeared (Tanner I). Then, a new treatment was started with IGF-I, MT, and BC for another 3 months. In this period, the degree of pubertal development increased to Tanner III (pubic level), without a known cause. (3) The treatment followed led to clear improvements in most of the initial abnormalities, perhaps due to the neurotrophic effect of IGF-I, the antioxidant effects of MT and BC, and the cerebral increase in the cyclic glycine-proline (cGP) achieved with administration of BC. (4) A continuous treatment with IGF-I, MT, and BC appears to be useful in RTT.

Modeling Rett Syndrome with Human Pluripotent Stem Cells: Mechanistic Outcomes and Future Clinical Perspectives

“…Moreover, a female patient with the missense mutation, R106W, showed a decreased symptomatology after the 6 months treatment with IGF-I, melatonin and also blackcurrant extracts, which contain cGP [ 105 ]. Interestingly, melatonin is a neurohormone that acts as a potent antioxidant, regarding its role as a free radical scavenger [ 106 ].…”

Transition from Animal-Based to Human Induced Pluripotent Stem Cells (iPSCs)-Based Models of Neurodevelopmental Disorders: Opportunities and Challenges

“…Insulin-like growth factor 1 (IGF-1), a drug that entered the clinical trial phase, showing safety, tolerability and mild efficacy in RTT girls in phase I (NCT01253317) but failing to show significant improvements in phase II (NCT01777542) [432], was previously applied to hIPSC-derived RTT neurons and rescued the reduction found in excitatory synapses [383]. In addition, a female patient carrying a MECP2 missense mutation revealed decreased symptomatology after 6 months of combined treatment with IGF1, melatonin and blackcurrant extracts [433]. Neurons derived from hIPSCs from patients with idiopathic ASD and matched controls were used to uncover the transcriptional changes induced by the treatment with IGF-1, both acutely and chronically.…”