In animals, IGF-1 treatment strongly affects CNS myelination at an early age, but is ineffective later on, suggesting that there is critical period for CNS myelination . Secondly, it must be noted that neurodegeneration and clinical buy Dapagliflozin course (maturation), are much faster in mice than in humans, for example, loss of vision occurs in mutant mouse at the age of 8 weeks and in humans at 8–18 months, respectively. There is no direct evidence about the therapeutic effect of IGF-1 in mice. However, the effect of IGF-1 has been tested in several human disorders. Positive effects
in adults have already been shown in body and brain growth [40–42], insulin resistance , and head Inhibitors,research,lifescience,medical injury . In children it was used in growth hormone insensitivity syndrome (Laron syndrome). In adolescents with type 1 diabetes it has been used to promote insulin sensitivity. Recently, a study of IGF-1 as therapeutic agent Inhibitors,research,lifescience,medical in Rett syndrome have been initiated in Children’s hospital, Boston
(Khwaja, Clinical Trials.Gov ID NCT01253317). Also growth hormone treatment which has its main effect through IGF-1 has shown to be favorable to the motor and cognitive effects in CP . The activity of free IGF-1 has been reported to be more active than Inhibitors,research,lifescience,medical IGF-1/IGFBP-3 . However, undesired acute adverse reactions and the absence of suitable IGF-1 preparations for treatment have become major concerns among pediatric endocrinologists worldwide. The main problems in IGF-1 treatment include BBB permeability, side-effects like hypoglycemia, and short intervals in administration of the drug. IGF-1 complexed with binding protein 3 (Somatokine R) used in this study was developed to prolong Inhibitors,research,lifescience,medical the half-life and reducing side effects (including hypoglycemia). Recombinant hormone seems to be safe even in prolonged therapy for growth hormone insensitivity syndrome or for short children . Our aim was to compare the biodistribution of free Inhibitors,research,lifescience,medical IGF-1, IGF-1/IGFBP-3, and IGF-1/NP complex in selected
organs over the time in Cln1-/- mouse model if IGF-1 could be used as a potential drug to treat INCL. It has been suspected that IGF-1/IGFBP-3 is too large to cross the BBB, but since IGF-1 is shed, it may eventually cross the BBB by specific transport systems [48, 49]. In Cln1-/- mice there is inflammation, and prominent alterations involved in the immune response [4, 9]. Consequently, in the Carnitine palmitoyltransferase II INCL patients, there might be inflammatory changes that could open BBB and the IGFs could cross it better than expected in healthy people. Earlier studies in mice have shown that IGF-1 injected as such is bound to the plasma proteins immediately after the injection forming different size of complexes and is cleared via the kidneys [50, 51]. In our biodistribution and pharmacokinetic studies iodinated IGF-1 was complexed to IGFBP-3 or nanoparticles in vitro before the injection.