New study confirms reduction of potent anti-inflammatory molecule α-MSH in patients with brain injury

Controlling inflammation with endogenous peptide may lessen damage

Zengen, Inc. announced today that its researchers have discovered that supplementation with alpha-Melanocyte-Stimulating Hormone (α-MSH), a naturally occurring molecule that modulates inflammatory and immune responses, may be beneficial in patients with brain injury.

Based on the knowledge that an inflammatory response occurs immediately after traumatic brain injury (TBI), Zengen scientists measured the levels of α-MSH in patients with acute TBI or subarachnoid hemorrhage (SAH). They discovered that blood concentrations of the α-MSH peptide are markedly reduced and remain steadily low during the first days after injury.

The findings, „a-Melanocyte-Stimulating Hormone is Decreased in Plasma of Patients with Acute Brain Injury,“ appear in the March 27, 2003 issue of the Journal of Neurotrauma, the official peer-reviewed journal of the National Neurotrauma Society.

„The present research confirms that an important endogenous anti-inflammatory mechanism is severely impaired during brain injury,“ stated Anna Catania, M.D., Professor of Endocrinology at the School of Internal Medicine, University of Milan and study co-author. „α-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.“

The study was designed to determine if there are changes in blood concentrations of α-MSH in patients with TBI or SAH. Concomitantly, clinical parameters and measured blood concentrations of the proinflammatory cytokine tumor necrosis factor-a (TNF-α) were recorded. Twenty-three patients were enrolled in the study (18 with TBI and 5 with SAH). Blood samples for determination of α-MSH and TNF-α were collected daily from day one to day four after injury.

Results show that baseline concentration of plasma α-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 α-MSH concentrations and the peptide remained consistently low over four post-injury days. Circulating TNF-α on day one was measurable in all patients and there was a negative correlation between plasma TNF-α and α-MSH. Plasma α-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 α-MSH, may lessen the extent of the injury,“ said James Lipton, Ph.D., study investigator, chief scientific officer and director of Zengen. „We are encouraged by these findings and will continue our research and development efforts on Zengen’s novel molecules based on α-MSH.“

Zengen’s novel molecules were developed from more than 25 years of original research in the US, Europe and Asia on peptide molecules derived from alpha-Melanocyte-Stimulating Hormone (α-MSH). Dr. Lipton and his collaborators first demonstrated that α-MSH possesses anti-inflammatory properties and uncovered the specific activity of the carboxy-terminal tripeptide region (C-terminal peptide) of the α-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.

About Traumatic Brain Injury (TBI)

According to the National Center for Injury Prevention and Control of the Centers for Disease Control and Prevention (CDC), 1.5 million people each year in the United States sustain a TBI. The result of a blow or jolt to the head which disrupts the normal function of the brain, TBIs are among the most likely types of injury to cause death or permanent disability. An estimated 50,000 people die annually from a TBI, and 80,000 to 90,000 people experience the onset of long-term disability or lifelong disability associated with a TBI. Vehicle crashes, firearm use and falls are the leading causes of TBI. At least 5.3 million Americans – 2 percent of the US population – currently live with disabilities resulting from TBI. Direct and indirect costs of TBI are estimated at $56.3 billion.