Mitochondrial Activity and HEPES II
T. Ronald Theodore
Integrated Biologics, LLC
Mitochondrial activity: HEPES and other zwitterions are true biological response modifiers. Years ago they were discovered by Dr. Norman Good at Roswell Park. It is interesting that he concentrated on their effects as a “buffer”. Dr. Good noted that HEPES and the other “Good buffers” increased the rate of oxidative phosphorylation in mitochondria. HEPES showed the greatest increase. I described the biological response modifying effects of HEPES “buffers” in 1998. Among the many effects of HEPES, it was shown that the compound induced “extramedullary hematopoiesis”. As much research is directed towards drugs that effect mitochondria – Perhaps it is time to look back at something that really works. For instance, if a compound can increase mitochondrial activity – what effect does this have on disease processes? Also the synergistic effect when used with other drugs may be very important. As we have shown HEPES induces bone marrow hypercellularity with increased immature cells and platelets, and extramedullary hematopoiesis. It has been shown to cross the blood-brain barrier. Could this be a source of embryonic like stem cells induced in an adult. Does it provide for a possible autologous transplant from a healthy family member to one that has a disease? Is there a possible use in rare diseases?
https://www.ncbi.nlm.nih.gov/pubmed/10851485 ;
https://www.ncbi.nlm.nih.gov/pubmed/10851486 .
We are currently focused on effects in traumatic brain injury and myocardial injury and repair. Review of the literature shows many positive reports of the compound effects in different disorders. We had suggested that HEPES might have an effect in TBI/CTE and Alzheimer’s disease many years ago. The recent similarities reported between the plaque seen in traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE) and the tau type plaque seen in Alzheimer’s are important. It has been shown that HEPES can reduce the plaque.
https://www.nature.com/articles/ncomms9997 ;
HEPES should be evaluated as a possible treatment in CT and Alzheimer’s disease.
The effect on myocardial injury was a potential area of research years ago. In fact early heart transplants were kept in HEPES solutions. It has been shown that myocardial damage was reduced by HEPES in coronary reperfusion staudies. https://www.ncbi.nlm.nih.gov/pubmed/10758820 . We are preparing studies to see if HEPES may be helpful in acute myocardial injury. We will also look at other effects on the ischemic heart. The possibility of scar reduction in the heart by HEPES should be studied. There are electrophysiologic effects that need study also.
Included are links to two publications that discuss some of these aspects. The drug is not expensive. It is readily available. It is easily prepared in qualified facilities. There is data available. It has been authorized for emergency use in humans under government permission and clinical trials.