Natural peptide may reduce damage from brain injury

Biopharmaceutical company Zengen announced this week that its researchers have discovered supplements of a naturally occurring hormone may be able to help patients with brain injury.

Alpha-Melanocyte-Stimulating Hormone (a-MSH) is a natural molecule that modulates inflammatory and immune responses. As an inflammatory response occurs immediately after traumatic brain injury (TBI), Zengen scientists measured the levels of a-MSH in patients with acute TBI or subarachnoid haemorrhage (SAH). They discovered that blood concentrations of the a-MSH peptide are markedly reduced and remain steadily low during the first days after injury.

"The present research confirms that an important endogenous anti-inflammatory mechanism is severely impaired during brain injury,"​ said Dr Anna Catania, professor of endocrinology at the School of Internal Medicine, University of Milan and study co-author.

"a-MSH is well-known for its potent anti-inflammatory influences within the brain and reduction in this circulating peptide may have detrimental consequences in brain injury,"​ added Catania.

TBI is caused by a blow or jolt to the head which disrupts the normal function of the brain. It is among the most likely types of injury to cause death or permanent disability.

The study was designed to determine if there are changes in blood concentrations of a-MSH in patients with TBI or SAH. Clinical parameters and measured blood concentrations of the proinflammatory cytokine tumour necrosis factor-a (TNF-a) were also recorded. Twenty-three patients were enrolled in the study (18 with TBI and 5 with SAH). Blood samples for determination of a-MSH and TNF-a were collected daily during the four days following injury.

Results, published in the 27 March issue of the Journal of Neurotrauma​, show that baseline concentration of plasma a-MSH in patients with acute brain injury of either traumatic or vascular origin was significantly lower than in controls. Patients with TBI or SAH had similar a-MSH concentrations and the peptide remained consistently low over four post-injury days. Circulating TNF-a on day one was measurable in all patients and there was a negative correlation between plasma TNF-a and a-MSH. Plasma a-MSH in eight TBI patients followed after the acute phase increased to the normal range.

"Controlling inflammation through administration of an endogenous anti-inflammatory molecule, such as a-MSH, may lessen the extent of the injury,"​ said Dr James Lipton, study investigator, chief scientific officer and director of Zengen​. He said that the company had been encouraged by the findings and would continue research and development on the novel molecules.

Dr Lipton and colleagues first demonstrated that a-MSH possesses anti-inflammatory properties and uncovered the specific activity of the carboxy-terminal tripeptide region (C-terminal peptide) of the a-MSH peptide. These discoveries led to the development of Zengen's proprietary peptide molecules, including CZEN 002, a synthetic octapeptide. Zengen is currently conducting phase I/II clinical trials with CZEN 002 in vaginitis.