Developing Gene Therapies and Molecular Studies: New Treatments for PA
PARnet is actively engaged in dialog with the following researchers and laboratories to promote new gene therapies and other forms of drug treatment for PA patients. Advances in research do not happen overnight, so ongoing support for these projects is critical for new PA treatments to be developed. PARnet is working with the Genetic Alliance, NIH and other organizations who promote translational research in an effort to accelerate new treatments coming to market for patients of rare disorders.
Funding Applications: Interested in Applying for Funds?
Please contact research@paresearch.org or paf@pafoundation.com to receive information about applying for a grant from the Propionic Acidemia Foundation and to receive a research funding proposal form. Your initial contact should include a brief description of your project including how your studies would improve the lives of PA patients.
The Use of Chaperones to Enhance PCC Assembly and Expression
Dr. Jan P. Kraus, Ph.D. Dept. of Pediatrics, University of Colorado School of Medicine, UCDHSC, Aurora, CO
Hua Jiang K., Sudhindra Rao, Vivien C. Yee, and Jan P. Kraus. Characterization of Four Variant Forms of Human Propionyl-CoA Carboxylase Expressed in Escherichia coli. (2005) J. Biol. Chem., Vol. 280, No. 30, 27719-27727.
Efforts are underway in the Kraus lab to understand how the enzyme PCC is assembled in vivo and to find options for correcting PA mutations that are defective in PCC assembly.
Correction of Novel Splicing Mutations in PCCA and PCCB
Dr. Magdalene Ugarte Ph.D., Dpto. Biologia Molecular, Centro do Biologia Molecular "Severo Ochoa", CSIC-UAM, Universidad Autonoma de Madrid, Madrid, Spain
Sonia Clavero, Belen Perez, Ana Rincon, Magdalene Ugarte, Lourdes Desviat. Qualitative and Quantitative Analysis of the Effect of Splicing Mutations in Propionic Acidemia Underlying Non-Severe Phenotypes. (2004) Hum. Genet. 115: 239-247.
The Ugarte lab has a long history of PA mutation identification and DNA analysis. Patients with splicing mutations in PCCA or PCCB have the potential of being treated if drugs can be developed to correct certain cellular splicing defects.
Dr. Toru Miyazaki, M.D., Ph.D. University of Tokyo, Tokyo Japan
Toru Miyazaki, Toshihiro Ohura, Makio Kobayashi, Yosuke Shigematsu, Seiji Yamaguchi, Yoichi Suzuki, Ikue Hata, Yoko Aoki, Xue Yang, Christina Minjares, Ikuko Haruta, Hirofumi Uto, Yuriko Ito, and Urs Mueller. Fatal Propionic Acidemia in Mice Lacking Propionyl-CoA Carboxylase and Its Rescue by Postnatal, Liver-specific Supplementation via a Transgene (2001) J. Biol. Chem., Vol. 276, Issue 38, 35995-35999.
Stem Cells Used to Deliver PCCA to Liver Ongoing studies in Dr. Miyazaki's lab are underway to find a method of using liver stem cells for PCCA delivery.
