PKU+Current+Research

Currently, having a Phe-restricted diet is the most effective treatment but there is research being done to come up with a cure that would minimize or even eliminate the Phe-sensitive diet. Families of patients have to alter their lifestyle to accommodate to the dietary needs of the patient, so having a long term treatment is needed and one example of this is somatic gene therapy (Ding, Georgiev, & Thöny, 2006).
 * Vector-Mediated Gene Transfer Study **

The use of adeno-associated virus (AAV) has been known to have prolonged effects on gene transfer without toxicity within the liver, muscle, and central nervous system (Ding, Georgiev, & Thöny, 2006). Experiments have been conducted on animal models such as mice to confirm these results. There are eight different AAV serotypes and AAV2 is the most researched and used among the human population. In correspondence to PKU, AAV serotype 2 and 5 were used for the gene transfer in the liver for two reports, so far, as a potential treatment. One concern with the results was that the females did not show as promising of results as did the males, but the difference between males and females was not statistically significant.

Ding et al. conducted their own experiment using a rAAV serotype 8 vector in hope of better results. The vector pAAV2-PKU-5 combined with capsids from serotype 8, also known as rAAV2-PKU-5/8, was inserted into 293T-cells of the 43 experimental mice through a vein and the PAH activity rose in comparison to the controls. Bothe males and females increased in PAH enzyme activity, but the females were a little higher than the males but not significantly. The dosage of 5 x 1012 virus particles was close to the dosage that has been shown to transduce almost all murine hepatocytes. The amount of AAV vector genomes found in each of the cells by quantitative Taqman-PCR analysis This in turn decreased the Phe levels in both the males and females to normal levels like that of the control after two weeks of the injection and continued to stay down after 42 weeks. The mice in this experiment had phenotype differences. The ones that were the wild-type controls had black hair, PKU mice had light brown hair, and the PKU infected but treated with the rAAV2-PKU-5/8 vector mice gradually went from light brown hair to dark brown and gradually darkened to black like the wild-type. AAV serotype 8 is more useful and poses better results than did serotype 2 or 5 in liver transduction and gene transfer to correct the PAH genes within the liver. Gene transfer has been very successful for other situations, so researchers have a goal to perform more experiments in order to get this form of treatment out to the public.

In some places that do not have the proper tests at birth to determine a PKU case diagnose children and adolescence with PKU after they have been portraying the symptoms for many years before taking action. Treatments that already exist would be antipsychotics and mood stabilizers, receptor 2α agonists, tricyclic antidepressants, and stimulant drugs such as Ritalin. There is always in need of improvements and for new ideas like buspirone that, in some studies, helps the control of hostility and aggressive behaviors from brain structural disorders and brain trauma and reducing anxiety and aggression in children that need an alternative drug. Researching this drug doesn’t only find out if this drug will become an alternative but also to further investigate the group of individuals with detailed interpretation (Fayyazi, Salari, Khajeh, & Gajarpour, 2014).
 * Comparison of Risperidone and Buspirone ** ** Study **

22 patients were assessed and split into 2 groups randomly. One group was treated with risperidone and the other with buspirone and each of the doses for the patients were gradually increased and then steady during an 8 week period. Once that session expired, the groups were then treated for another 8 weeks with the drug that most accommodated their specific symptoms of PKU. The results were assessed by the NCBRF and the 7-point CGI through questions asked from a therapist (Fayyazi, Salari, Khajeh, & Gajarpour, 2014).

Risperidone showed to be effective in the control of hyperactivity, disruptive/stereotypic behaviors, and conduct problems in all the patients with PKU in comparison to the before and after treatment. Buspirone was only effective in the control of hyperactivity in comparison to the before and after treatment. In comparison between the two drugs, risperidone was more effective in treating hyperactivity, dispruotive/stereotypic, self-isolation, and insecure/anxious symptoms. The main purpose of the drugs was to reduce anxiety, but risperidone was the most effective in the study. Some of the symptoms have then been determined that they are from the environment that each patient lives in on a daily basis. Even though the risperidone is a better option for common symptoms, buspirone could be an alternative when risperidone in ineffective (Fayyazi, Salari, Khajeh, & Gajarpour, 2014).

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