PKAN clinical trial in USA and Canada to start in December 2019

For several years, the research teams of Dr. Susan Hayflick (University of Oregon, Portland, USA) and Prof. Ody Sibon (University of Groningen, NL) have been working on a new drug for PKAN and the further decoding of PKAN disease mechanisms. Now the time has come: the start of the long-awaited clinical CoA-Z study under the direction of Dr. Penny Hogarth (University of Oregon, Portland, USA) is imminent. Enrollment of patients in the USA and Canada is scheduled to begin in mid-December.
A few years ago, female scientists in the USA set up the Spoonbill Foundation and in the Netherlands the Stichting Lepelaar was founded. Their aim was to use these charitable foundations to raise money to finance a study and to make the new drug available to PKAN patients as cost-effectively as possible in the long term by taking all the steps of drug development into their own hands.

New insights into disease mechanisms and treatment options for PKAN

Two groundbreaking new publications have recently appeared that complement each other. They scientifically underpin the therapeutic approach pursued with the Coa-Z study, as the two research teams in Portland and Groningen were able to shed further light on the disease mechanisms of PKAN with surprising new findings.
The drug 4'-phosphopantetheine, called CoA-Z, targets the coenzyme A synthesis impaired by the defect in the PANK2 gene, which triggers a cascade of faulty metabolic processes in the mitochondria of the globus pallidus. It is not that too little coenzyme A is generally formed, but rather that the mitochondrial acyl carrier protein required for fatty acid synthesis shows reduced activity due to a possibly too slow co-A synthesis. This in turn leads to further impairment of mitochondrial function and ultimately to iron deposits.
In the cells of PKAN knockout mice and in the skin cells of PKAN patients, so-called biomarkers were used to demonstrate that the biological malfunctions in these cells were completely normalized when CoA-Z was administered. This gives us hope that we have finally found a drug that could help patients. But we will only know for sure after a clinical study with a high scientific significance.

Below you will find links to the original publications and patient-oriented explanations:

• Article from Dr. Hayflick's team: https://www.embopress.org/doi/10.15252/emmm.201910489
  Explanatory notes: http://nbiacure.org/coaz-clinical-trial/coa-z-paper-faqs/
• Article by Dr. Sibon's team: https://www.embopress.org/doi/10.15252/emmm.201910488
  Explanatory notes: http://nbiacure.org/coaz-clinical-trial/coamtacp-pdh-pathway-paper-faqs/

Unfortunately, PKAN patients in Germany and many other countries still have to be patient. For the time being, all that remains is the hope that the CoA-Z study will take a promising course and that patients outside the North American continent can also be included in an extension of the study as soon as possible.