A naturally occuring peptide may lead to drug therapies for traumatic brain injury, stroke and heart attack, scientists say.
Strokes, heart attacks and traumatic brain injuries are separate diseases with certain shared pathologies that achieve a common end – cell death and human injury due to hypoxia, or lack of oxygen.
In these diseases, a lack of blood supply to affected tissues begins a signalling pathway that ultimately halts the production of energy-releasing ATP molecules – a death sentence for most cells.
By employing derivatives of humanin, a naturally occurring peptide encoded in the genome of cellular mitochondria, researchers at Ben Gurion University of the Negev in Beer-Sheva, Israel, are working to interrupt this process, buying precious time for tissues whose cellular mechanisms have called it quits.
“The present findings could provide a new lead compound for the development of drug therapies for necrosis-related diseases such as traumatic brain injury, stroke and myocardial infarction – conditions for which no effective drug-based treatments are currently available [that work by blocking necrosis],” said Abraham Parola, a professor of biophysical chemistry at Ben Gurion University of the Negev.
The humanin derivatives work by counteracting the decrease in ATP levels caused by necrosis. The researchers tested the effectiveness of the humanin analogues by treating neuronal cells with these peptides prior to exposure to a necrotic agent.
The experiments were a success, researchers said.
Parola and his colleagues also performed in vivo studies by treating mice that had had traumatic brain injuries with an HNG17 analogue, which successfully reduced cranial fluid buildup and lowered the mice’s neuronal severity scores, a metric in which a higher number corresponds with greater degrees of neurological motor impairment.
As the peptides Parola and his colleagues used are derivatives of naturally occurring humanin, an ideal treatment might involve a drug delivery system with the HNG17 as the lead compound, a process aided by the ability of the peptides to penetrate the cell membrane without the use of additional reagents.
The work will be presented at a meeting of the Biophysical Society in Baltimore.