November 2019
NBIA researchers Drs. Susan Hayflick and Penny Hogarth recently announced that, thanks to added help from a federal grant, they will soon launch a clinical trial to test a compound, CoA-Z, in individuals with PKAN, a common form of NBIA.
The grant is from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health.
The CoA-Z compound will be tested in the U.S. and Canada to see if it corrects a metabolic process involved in producing coenzyme A in individuals with PKAN.
To prepare for the trial, the researchers recently did a study in a small number of PKAN adults and children who received CoA-Z under supervision at the Oregon Health & Sciences University, where the Hayflick and Hogarth Team is located. The information gained from this study was used to refine the dosing plan for the trial and help determine when blood samples should be collected.
The preliminary testing confirmed that CoA-Z was safe for PKAN individuals to take over the short period of the study.
In addition to the NIH grant that will fund the clinical trial over a period of several years, $2 million in donations has been raised from a variety of sources over the past two years to support the manufacturing and formulation of CoA-Z, database development and other costs not covered by the NIH grant. NBIA families held many fundraisers, with proceeds going to the nonprofit Spoonbill Foundation founded by Hayflick and Hogarth. Funds also came from Stichting Lepelaar, a nonprofit Drs. Ody Sibon and Hans Hektor set up in the Netherlands, the Dutch Foundation for Rare Diseases, and $50,000 from the NBIA Disorders Association.
The OHSU team led by Suh Young Jeong, PhD, in partnership with Sibon's group, recently published an article in the journal EMBO Molecular Medicine on CoA-Z, titled "4'-Phosphopantetheine corrects CoA, iron, and dopamine metabolic defects in mammalian models of PKAN." The article was based on a mouse model of PKAN. The researchers say this mouse is important because it is the first to show abnormal iron accumulation in the brain, as well as other PKAN changes.
These mice did not have any dystonia, but they had biochemical changes of PKAN in the same brain region as in people with PKAN. According to the article, after taking 4'-phosphopantetheine by mouth for two weeks, all of the PKAN biochemical changes in mouse brain improved.
Researchers also tested skin cells from people with PKAN, and the same biochemical changes were found. When the cells were bathed in 4'-phosphopantetheine, the changes resolved. The mouse experiments showed that 4'-phosphopantetheine is not degraded in the gastrointestinal tract and that it can cross the blood-brain barrier.
Sibon's group published a separate paper in the same journal issue titled, "CoA-dependent activation of mitochondrial acyl carrier protein links four neurodegenerative diseases," that reveals important insights into the biochemical changes in PKAN and related disorders. The researchers believe these two publications provide a solid foundation for launching studies of CoA-Z in people.
Information for this article was taken from http://nbiacure.org/coaz-clinical-trial/ where you can go for more information and updates on the clinical trial.
