I liked this paper because it takes Prana and PBT2 to help also cardiac problems. Now Prana is selecting the " more clinical indications " . Most likely these results were known to Prana already for many months. PBT2 has proven to be safe in the human studies and so it could well be taken to cardiac clinical studies. So it looks to me that PBT2 prevents the mitochondrial damage in this experimental model. The oxidation lab results will be very interesting one day.
See comment in PubMed Commons below
Antioxid Redox Signal. 2017 Mar 3. doi: 10.1089/ars.2016.6848. [Epub ahead of print]
Cardiac Light Chain Amyloidosis: The Role of Metal Ions in Oxidative Stress and Mitochondrial Damage.
Diomede L1,
Romeo M1,
Rognoni P2,
Beeg M1,
Foray C3,
Ghibaudi E4,
Palladini G2,5,
Cherny RA6,7,
Verga L8,
Capello GL8,
Perfetti V9,
Fiordaliso F3,
Merlini G2,5,
Salmona M1.
Author information
- 11 Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri ," Milan, Italy .
- 22 Amyloid Research and Treatment Center , Foundation IRCCS Policlinico San Matteo, Pavia, Italy .
- 33 Bio-imaging Unit, Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri ," Milan, Italy .
- 44 Department of Chemistry, University of Turin , Turin, Italy .
- 55 Department of Molecular Medicine, University of Pavia , Pavia, Italy .
- 66 The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Royal Pde, Parkville, Australia .
- 77 Prana Biotechnology Ltd. , Parkville, Australia .
- 88 Pathologic Unit, Foundation IRCCS Policlinico San Matteo , Pavia, Italy .
- 99 Medical Oncology Unit, Foundation IRCCS Policlinico San Matteo , Pavia, Italy .
Abstract
AIMS:
The knowledge of the mechanism underlying the cardiac damage in immunoglobulin light chain (LC) amyloidosis (AL) is essential to develop novel therapies and improve patients' outcome. Although an active role of reactive oxygen species (ROS) in LC-induced cardiotoxicity has already been envisaged, the actual mechanisms behind their generation remain elusive. This study was aimed at further dissecting the action of ROS generated by cardiotoxic LC in vivo and investigating whether transition metal ions are involved in this process. In the absence of reliable vertebrate model of AL, we used the nematode Caenorhabditis elegans, whose pharynx is an "ancestral heart."
RESULTS:
LC purified from patients with severe cardiac involvement intrinsically generated high levels of ROS and when administered to C. elegans induced ROS production, activation of the DAF-16/forkhead transcription factor (FOXO) pathway, and expression of proteins involved in stress resistance and survival. Profound functional and structural ROS-mediated mitochondrial damage, similar to that observed in amyloid-affected hearts from AL patients, was observed. All these effects were entirely dependent on the presence of metal ions since addition of metal chelator or metal-binding 8-hydroxyquinoline compounds (chelex, PBT2, and clioquinol) permanently blocked the ROS production and prevented the cardiotoxic effects of amyloid LC. Innovation and Conclusion: Our findings identify the key role of metal ions in driving the ROS-mediated toxic effects of LC. This is a novel conceptual advance that paves the way for new pharmacological strategies aimed at not only counteracting but also totally inhibiting the vicious cycle of redox damage.
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