Prior to becoming a 501(c)3, the PAF established a Propionic Acidemia Fund at UT Southwestern Medical Center in Dallas, Texas to promote the studies of Dr. Toru Miyazaki. With PAF’s help, this fund raised over $90,000. Dr. Miyazaki has succeeded in constructing a mutant mouse model of PA. The construction of this mouse model is significant because scientists now have a valuable tool to observe PA gene manipulation in an animal with propionic acidemia. This allows researchers to evaluate the function of genes transferred into the animal and to see how the body responds. Experiments in mice must precede human clinical trials involving gene therapy, so it is extremely important for this research to be performed.

Two genes, PCCA and PCCB are necessary for the production of propionyl-CoA carboxylase (PCC) an enzyme involved in the metabolism of the amino acids methionine, threonine, isoleucine and valine. Dr. Miyazaki’s mouse model contains a mutation in PCCA and these mice are unable to make PCC. PA mutant mice exhibit symptoms of propionic acidemia similar to human PA patients including poor feeding, dehydration and accelerated ketosis progressing towards death.

Dr. Miyazaki has confirmed that supplementation of 15-20% PCC (propionyl-CoA carboxylase) enzyme activity via a transgene to PA mice resulted in abolishment of most PA symptoms. Treated mice were able to consume a normal diet containing a high level of protein. Additionally they grew and developed like normal mice, procreated and lived a normal lifespan.

There is currently no research being done at UT Southwestern on Propionic Acidemia. Those interested in reading more about Dr. Miyazaki’s studies may visit the sites below.

• Published PA research by Dr. Miyazaki:Fatal Propionic Acidemia in Mice Lacking Propionyl-Coa Carboxlase and Its Rescue by Postnatal, Liver-specific Supplementation via a Transgene

• UT Southwestern Medical Center Press Release