Kaohsiung Medical University

Academia Sinica

China Medical College Hospital

Jan-Gowth Chang

Yuh-Jyh Jong

Hung Li

Shou-Mei Wu

Hsiu-Mei Hsieh-Li

Chun-Chiu Wang

Chun-Nan Lin

Shyh-Chyun Yang

Fuu-Jen Tsai

A-Mei Huang

Shih-Hsien Hsu

Tzyh-Chyuan Hour

Yeong-Shiau Pu

Yung-Fu Chang

Ting-Yuan Liu

Kai-Wei Lin

Chung-Yee You

Wen-Kuang Yang

The present invention relates to a method of regulating the expression level of survival of motor neuron 1 (SMN1) comprising administering to a subject in need thereof a therapeutically effective amount of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) regulator and a pharmaceutically acceptable carrier. The present invention also relates to a method of detecting enzyme activity of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in human fibroblasts comprising detecting protein expression level of survival of motor neuron 1 (SMN1).

Method of regulating the expression level of survival of motor neuron 1

A nucleic acid construct comprising a genetic engineered heterogeneous nuclear ribonucleoprotein (hnRNP) A1 gene is provided. A transgenic mouse in which the expression of hnRNP A1 gene has been disrupted is also provided. The mouse is useful for studying the role of hnRNP A1 gene in normal and disease states of a developmental disorder and muscular diseases. Therefore, a method of screening a compound for potential use in prevention and/or treatment of developmental disorder and muscular diseases is further provided.

hnRNP A1 knockout animal model and use thereof

The present invention is correlated with a derivative of 18&#x3b2;-glycyrrhetinic acid apt to suppressing cancer cells, which is selected from a group comprising of structure I and structure II: wherein residue Ris selected from one of CHand CHCH, residue Ris selected from one of COOCH, COOCHCH, COOCH(CH), CONHCHCH, CONHCHCHCH, and CONHCH(CH), and residue Ris selected from one of COOCHCH, COOCH(CH), CONHCHCH, CONHCHCHCH, and CONHCH(CH).

Derivative of 18&#x3b2;-glycyrrhetinic acid apt to suppress cancer cells

A method of treating spinal muscular atrophy. The method includes administering an effective amount of composition including a sodium-proton exchanger inhibitor and a pharmaceutically acceptable carrier or salt, to a subject with spinal muscular atrophy to ameliorate a symptom of spinal muscular atrophy.

Treatment for spinal muscular atrophy

A method for diagnosing spinal muscular atrophy is provided. The method includes providing a biological sample of a subject containing a nucleotide of SMN gene, amplifying SMN exons, andby a universal multiplex PCR using the nucleotide as a template and the primers to obtain fragments of the SMN exons, and, labeling the fragments of the SMN exons, andby a fluorescent primer to obtain fluorescence-labeled exon fragments, and analyzing the fluorescence-labeled exon fragments by a capillary electrophoresis. If the SMN1/SMN2 ratios in exonandare different, it indicates that the subject is susceptible to spinal muscular atrophy. Additionally, if the peak of certain exon fragment appears crossed, it indicates an intragenic mutation in the exon.

Method for diagnosing spinal muscular atrophy

A method for diagnosing spinal muscular atrophy is provided. The method includes providing a biological sample of a subject containing a nucleotide of SMN gene, amplifying SMN exons 1, 2a, 2b, 3, 4, 5, 6, 7, and 8 by a universal multiplex PCR using the nucleotide as a template and the primers to obtain fragments of the SMN exons 1, 2a, 2b, 3, 4, 5, 6, 7, and 8, labeling the fragments of the SMN exons 1, 2a, 2b, 3, 4, 5, 6, 7, and 8 by a fluorescent primer to obtain fluorescence-labeled exon fragments, and analyzing the fluorescence-labeled exon fragments by a capillary electrophoresis. If the SMN1/SMN2 ratios in exon 7 and 8 are different, it indicates that the subject is susceptible to spinal muscular atrophy. Additionally, if the peak of certain exon fragment appears crossed, it indicates an intragenic mutation in the exon.

The invention features a method of modulating SMN exon 7 expression in a subject by administering hydroxyurea to the subject.

Hydroxyurea treatment for spinal muscular atrophy

The invention features a method of modulating SMN exon 7 expression in a subject by administering a histone deacetylase inhibitor.

Treatments for spinal muscular atrophy

A genetically engineered mouse model that genotypically and phenotypically mimics human patients with spinal muscular atrophy. The genome of the mouse model contains at least one mutation that knockouts the native mouse Smn gene and at least one copy of human SMN,gene that functions in a murine background and compensates for the loss of the functions provided by the Smn gene. The phenotypes of said mouse model can be grouped according to their severity of pathological conditions into three types, paralleling the three types of human spinal muscular atrophy conditions. Said mouse model can be used for studying the pathophysiology of spinal muscular atrophy and for developing and testing existing and new therapeutic and diagnostic methods.

Growing community of inventors

Kaohsiung, Taiwan

Jan-Gowth Chang