Jan P. Kraus, Ph.D.  University of Colorado at Denver and Health Sciences Center,(UCDHSC) Denver, Colorado. 

"Genotype-phenotype correlations in Propionic Acidemia" - In July 2008, PAF awarded Dr. Kraus a $40,000 grant.  

"Crystallization and structure determination of human propionyl-CoA carboxylase"   - In March 2008, PAF awarded Dr. Kraus a $30,000 grant.

Jon Wolff, University of Wisconsin Madison, Wisconsin

"Muscle directed gene therapy for Propionic Acidemia"

In 2007, PAF awarded Dr. Wolff a $30,000 grant.   More information is available in the April 2007 newsletter. 

Dr. Michael Barry, Ph.D. Mayo Clinic, Rochester, MN

"Gene Therapy for Propionyl CoA Carboxylase Deficiency"

Preclinical studies by Dr. Miyazaki and liver transplantation in PA patients suggest that correction of the defective genes of PCC in the liver can temper some of the metabolic problems due to the disease.  Based on this, Dr. Michael Barry is testing the feasibility of performing liver-directed gene therapy using adenoviral and adeno-associated virus gene delivery vectors using PA mice constructed by Dr. Miyazaki.  Work is underway to determine if these liver-directed approaches can mitigate the metabolic defects in the mice and how long the genetic correction will last.  While at Baylor College of Medicine, Dr. Barry's project was funded $58,489.04.    (2004-2006)  An additional $25,000 was awarded to Dr. Barry for 1/1/2007-12/31/2007 to continue his studies at Mayo Clinic.

August 2006 Progress Update as seen in the PAF Newsletter

Previously Funded Research

Jan P. Kraus, Ph.D.  University of Colorado at Denver and Health Sciences Center,(UCDHSC) Aurora, Colorado.   Grant 3/1/2006- 2/29/2008

"Therapeutic Approaches to Propionic Acidemia”

In 2006, PAF awarded Dr. Kraus a grant for $25,000 for his studies with chaperone proteins.  An additional $30,000 was awarded in 2007.  The enzyme propionyl-CoA carboxylase (PCC) is deficient in pathogenic cases of propionic acidemia.  PCC is constructed from alpha and beta subunits encoded by the genes PCCA and PCCB respectively.  To produce a functional enzyme the subunits must be assembled and folded into the correct conformation inside the body.   Some mutant forms of PCC tend to aggregate or fold incorrectly resulting in inactive enzymes in some PA patients.  Previous work has shown that when some misfolded mutant PCCs are expressed in the presence of the molecular chaperone proteins GroES and GroEL significant levels of PCC activity are produced.  Treatment of this class of PCC mutants with chemical chaperones also restored PCC activity.  This indicates that in a subclass of PCC mutations, the defect lies in the impaired folding or assembly of the enzyme rather than in its production.  Dr. Kraus is currently treating specific PCC mutants in E. coli and in fibroblasts with molecular and chemical chaperones to identify mutants that may respond in vivo.  If increased production of PCC is demonstrated, this work has the potential to open the doors to a new treatment strategy for some PA patients. 

August 2006 Progress Update as seen in the PAF Newsletter

About PCC  

List of PCCA Mutations

List of PCCB Mutations

Dr. Toru Miyazaki, M.D., Ph.D. The University of Texas Southwestern Medical Center, Dallas, Texas

Other Important PA Research/Studies

Dr. Mendel Tuchman, Children's National Medical Center, Washington, D.C. 

N-carbamylglutamate markedly enhances ureagenesis in N-acetylglutamate deficiency and propionic acidemia as measured by isotopic incorporation and blood biomarkers.

N-carbamylglutamate can potentially improve hyperammonemia in patients with propionic and methylmalonic acidemia - From the August 2006 PAF Newsletter.

For information from a family that has participated, email paf@pafoundation.com

You can still participate in this study.

Dr. Nicola Longo, University of Utah

Anaplerotic Therapy in Propionic Acidemia - The objective of this project is to define whether nutritional supplements (ornithine alphaketoglutarate,
glutamine, or citrate) capable of filling-up the citric acid cycle
(anaplerotic therapy) can improve hyperammonemia, glutamine levels, and
outcome in patients with propionic acidemia.  You can read more in the Spring 2008 newsletter on the Sites of Interest Page.

Current Research List

This document contains a list of journal articles with information on Propionic Acidemia.    

PA Current Research List (new web page with links to articles-click on authors to link to the article)

PA Current Research List (PDF) - so you can print it.

The Importance of Research (click HERE)

Interested in Applying for Research Funds?

In addition to scientific studies, PAF is looking for clinical studies on complications of propionic acidemia including: 

Cardiomyopathy

Genotype phenotype studies

Long QT

Hyperammonemia

Neutropenia

Pancreatitis

Secondary immune deficiency

Treatment

Gut microbial flora control

Gastrointestinal motility

In order to encourage clinical studies, PAF is working with Coriell to help establish a public worldwide repository of DNA and clincal data.  We encourage all investigators working towards a cure or better treatments for propionic acidemia to contact the Propionic Acidemia Foundation for possible funding. Grant applications may be downloaded by clicking on Format for PAF Research Funding Proposals.

Grant applications should be submitted by October 1st.   All applications will be reviewed by the Propionic Acidemia Foundation Medical Advisory Board.   Grant determinations will be made in January.

If you have any additional questions regarding applications and funding regulations, please email research@pafoundation.com

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