Another interesting implication of the work by Cartier

Another interesting implication of the work by Cartier and colleagues lies in unraveling the therapeutic potential of DA reverse transport in autism. Starting from the observation that rare autism-causing variants are associated with inhibition of reverse transport of DA, it could be hypothesized that psychostimulants may serve as a potential therapeutic aid in autism. Notably, not only have psychostimulants been suggested to be effective for ADHD-like symptoms in autism spectrum disorder individuals, but the prevalence rates of their use in autism are also strikingly increasing (). It should be noted, however, that AMPH (which is known to cause reverse transport of DA) has been also shown to elicit autism-like symptoms including stereotyped behaviors and social impairments in animal models (). Based on this evidence, the conclusion that increasing the reverse transport of DA could represent a novel therapeutic target in autism per se (and not for the ADHD-like symptoms in autism) is probably too premature. However, it is becoming increasingly clear that the reverse transport of DA could be one of the key mechanisms involved in the fine-tuning of DA levels in the synapse. In this scenario, the work by Cartier and colleagues is relevant in unraveling how disruption of such synaptic dopaminergic fine-tuning could ultimately result in autism. Author Contribution
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The past two decades have seen most research efforts targeted at correcting the ion transport deficiency of buy Ezetimibe (CF), highlighting the required promotion and development of new drugs to tackle CF (). The polyexocrinopathy genetic disease CF is caused by one of the 2000 documented mutations in the cystic fibrosis transmembrane conductance regulator gene (, OMIM #) among them the deletion F508 (F508del-CFTR) is the most common and severe CF mutation (). F508del causes CFTR misfolding/instability leading to defective protein biosynthesis, reduced plasma membrane residence and altered channel gating (). Whereas it remains unclear whether current small molecules targeting F508del-CFTR will have therapeutic benefit, the wind is nevertheless changing for CF patients who are still awaiting a curative treatment. Indeed, new medications with orphan drug status are, for some, rapidly progressing in clinical trials (), among them the F508del-CFTR corrector lumacaftor (VX-809) (). Acceleration of drug development has been clearly encouraged by the recent successful marketing of Kalydeco®, the first personalized medication for CF patients directly targeting mutated CFTR proteins (). The CF mutations can be classified into six classes () helping research to being directed toward mutation-specific therapeutic agents. The most severe cases of CF belong to classes I, II and III, where little or no cAMP-dependent CFTR-mediated chloride ion transport is observed in epithelia expressing CFTR mutants. Mutations that have not been fully analyzed yet will be characterized as mutations of unknown clinical significance. Despite the fact that F508del-CFTR is the main target for drug development in CF (), categorizing about 2000 individual mutations identified so far in patients worldwide would be a tough job while still remaining an important challenge. It is also necessary to understand whether the mutation themselves can cause CF or not, or a CF-related disease (e.g., congenital bilateral absence of the vas deferens or CBAVD, or pancreatitis). For CF patients with a heterozygous genotype, it is also important to understand whether carrying a CF-causing mutation actually results in CF or not. In theory, the goal for such a classification is to predict the phenotype of a CF patient according to his/her genotype, but in practice this critically depends on our ability to functionally characterize the mutant CFTR. But, not all the CF mutations have been classified so far because the function of CFTR remains unknown for many of them. Equally important is the perspective, raising on the horizon, to propose a personalized medication according to the mutation(s) (). Although controversial, predicting drug-induced response is indeed an attractive challenge that might well be added to (or even better replace) the therapeutic arsenal against the disease ().