کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10833945 | 1065836 | 2011 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Evaluation of orally administered PEGylated phenylalanine ammonia lyase in mice for the treatment of Phenylketonuria
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کلمات کلیدی
PALPHEPKUPTDNOFAnabaena variabilisphenylketonuria - فنیل کتونوریProtein transduction domains - دامنه های انتقال پروتئینpharmacodynamic - فارماکودینامیکPhenylalanine ammonia lyase - فنیل آلانین آمونیاک لیائازPhenylalanine hydroxylase - فنیلالانین هیدروکسیلازPhenylalanine - فنیلآلانینHPA - میلی بار یا هکتوپاسکالHyperphenylalaninemia - هیپرفنیلالانینمی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Evaluation of orally administered PEGylated phenylalanine ammonia lyase in mice for the treatment of Phenylketonuria Evaluation of orally administered PEGylated phenylalanine ammonia lyase in mice for the treatment of Phenylketonuria](/preview/png/10833945.png)
چکیده انگلیسی
Phenylketonuria (PKU), a Mendelian autosomal recessive phenotype (OMIM 261600), is an inborn error of metabolism causing impaired postnatal cognitive development in the absence of treatment. We used the Pahenu2/enu2 PKU mouse model to study oral enzyme substitution therapy with various chemically modified formulations of phenylalanine ammonia lyase (Av-p.C503S/p.C565S/p.F18A PAL). In vivo studies with the most therapeutically effective formulation (5 kDa PEG-Av-p.C503S/p.C565S/p.F18A PAL) revealed that this conjugate, given orally, yielded statistically significant (p = 0.0029) and therapeutically relevant reduction (~ 40%) in plasma phenylalanine (Phe) levels. Phe reduction occurred in a dose- and loading-dependent manner; sustained clinically and statistically significant reduction of plasma Phe levels was observed with treatment ranging between 0.3 IU and 9 IU and with more frequent and smaller dosings. Oral PAL therapy could potentially serve as an adjunct therapy, perhaps with dietary treatment, and will work independently of phenylalanine hydroxylase (PAH), correcting such forms of hyperphenylalaninemias regardless of the PAH mutations carried by the patient.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 104, Issue 3, November 2011, Pages 249-254
Journal: Molecular Genetics and Metabolism - Volume 104, Issue 3, November 2011, Pages 249-254
نویسندگان
Christineh N. Sarkissian, Tse Siang Kang, Alejandra Gámez, Charles R. Scriver, Raymond C. Stevens,