Medical Student Research Fellowship for Summer 2011

Mentor: Andrew Pieper, MD PhD            
Department: Psychiatry and Biochemistry
Room number: L4.260       
Mail Code:     9152  
Phone number: 214-648-2538     
E-mail: Andrew.Pieper@UT Southwestern.edu           
Project title:   In Vivo Identification of Pharmacologic Agents for Treatment of Rett Syndrome

Human subjects IRB approved project number (where applicable): n/a
Animal subjects IRB approved project number (where applicable):  2008-0347

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)  Patient Based Research

Brief Description of Project: 

Rett Syndrome (RTT) is a devastating X-linked neurological disorder that afflicts approximately 1 in 10,000 females, RTT is characterized by the sudden onset of symptoms in late postnatal development (6-18 months), including deceleration in head growth accompanied by autonomic dysfunctions in breathing and digestion, anxiety, seizures, progressive loss of motor and language skills, stereotypic hand movements, muscle hypotonia, and severe cognitive impairment or mental retardation.  Roughly 85% of RTT cases are caused by a mutation in the gene encoding methyl CpG-binding protein 2 (MECP 2), a global regulator of transcription that is highly expressed in the central nervous system.  Deletion of the Mecp2 gene in mouse models is sufficient to cause Rett-like symptoms.  There are currently no effective treatments for RTT, but the disease phenotype is rescued by activation of Mecp2 at later stages of the disease in mice in which this gene has been genetically silenced.  This reversal of symptoms underscores the opportunity for therapeutic intervention at later stages of the disease.  We are conducting an in vivo screen to identify drugs and drug-like compounds that ameliorate symptoms in a mouse model of RTT.  Mecp2 mice and wildtype littermates are treated with CNS-active FDA-approved drugs and drug-like molecules from the UTSWMC Chemical Compound Library.  The student administers drugs to mice and evaluates the mice weekly for general condition and neurological function, breathing function, locomotor activity, and survival. 

Previous Research Activities or Publications with Medical Students:

Pieper, A. A., Xie, S., Capota, E., Estill, S.J., Zhong, J., Long, J.M., Becker, G.L., Huntington, P., Goldman, S.E., Shen, C.H., Capota, M., Britt, J.K., Hsieh, J., De Brabander, J., Ready, J.M. and McKnight, S.L. (2010). Discovery of a Proneurogenic, Neuroprotective Chemical. Cell 142:39-51