Clinical Trials

Ann N Y Acad Sci. 1987;496:608-19.

Enkephalins and T-cell enhancement in normal volunteers and cancer patients.

Plotnikoff NP, Miller GC, Nimeh N, Faith RE, Murgo AJ, Wybran J.

PMID: 3496830

Ann N Y Acad Sci. 1987;496:108-14.

Immunologic properties of methionine-enkephalin, and therapeutic implications in AIDS, ARC, and cancer.

Wybran J, Schandené L, Van Vooren JP, Vandermoten G, Latinne D, Sonnet J, De Bruyère M, Taelman H, Plotnikoff NP.

PMID: 3496822

Am Fam Physician. 1989 Sep;40(3):234.

Methionine-enkephalin shows promise in reducing HIV in blood.

Plotnikoff N, Wybran J.

PMID: 2773759

Stress and Immunity

Wybran J, Plotnikoff NP

Plotnikoff, N.J., Murgo, A.J., Faith, R., Wybran, J. (Eds.)

Methionine-Enkephalin, A New Lymphokine for the Treatment of ARC Patients

Boca Raton: CRC Press, 1991

Cytokines Stress & Immunity

Bihari B, Plotnikoff NP.

Plotnikoff NP, Murgo A, Faith RE, Good RA (Editors)

Methionine Enkephalin in the Treatment of AIDS-Related Complex

CRC Press, Inc. Boca Raton, FL, 1999

Acta Neurol (Napoli). 1991 Oct;13(5):433-41.

Enkephalins and immune inflammatory reactions.

Jankovic BD.

Immunology Research Center, Belgrade, Yugoslavia.

Methionine-enkephalin (Met-Enk) and leucine-enkephalin (Leu-Enk) belong to family of opioid peptides. In vivo studies on immunomodulating activity of enkephalins performed in the rat revealed the following: (a) both neuropentapeptides showed a dual, dose-dependent effect, i.e., high doses suppressed while low doses potentiated immune responses; (b) Met-Enk is more potent immunomodulator than Leu-Enk; (c) high doses of Met-Enk suppressed immune inflammatory reactions, such as systemic anaphylactic shock, Arthus and delayed hypersensitivity skin reactions to protein antigen, allograft rejection, adjuvant arthritis, and experimental allergic encephalomyelitis. Met-Enk is more efficient when applied intracerebroventricularly. A preliminary clinical trial showed that intrathecally given Met-Enk exerted a beneficial effect on 13 patients with chronic severe progressive multiple sclerosis.

PMID: 1663693

Clin Immunol Immunopathol. 1997 Feb;82(2):93-101.

Methionine enkephalin: a new cytokine--human studies.

Plotnikoff NP, Faith RE, Murgo AJ, Herberman RB, Good RA.

College of Medicine and College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, 60612, USA.

The effects of methionine enkephalin (met-enkephalin) on human immune function are reviewed. This pentapeptide functions to upregulate, or enhance, immune function in the majority of donor samples at low doses and suppresses at high doses. The influence of this molecule is shared by the central nervous, neuroendocrine, and immune systems. Cells from each of these systems possess receptors for met-enkephalin and have the ability to process met-enkephalin from its prohormone, proenkephalin A. Studies have shown that this molecule is capable of enhancing immune function in patients with cancer or AIDS. It is proposed that this molecule be classified as a cytokine.

PMID: 9000477

International Journal of Thymology, 1997;Vol 5 No. 9-9; pp448-464

Peptid-M (LUPEX)Immunotherapy in Multiple Sclerosis, Optic Neuritis and Uveitis

Stambuk N et al

Anticancer Drugs. 2004 Mar;15(3):203-9.

Treatment of advanced pancreatic cancer with opioid growth factor: phase I.

Smith JP, Conter RL, Bingaman SI, Harvey HA, Mauger DT, Ahmad M, Demers LM, Stanley WB, McLaughlin PJ, Zagon IS.

Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.

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Opioid growth factor (OGF) is an endogenous pentapeptide that inhibits growth of human pancreatic cancer cells in culture, as well as xenografts in nude mice. To establish the maximum tolerated dose (MTD), and determine safety and toxicity of OGF, a phase I trial was performed in patients with advanced unresectable pancreatic cancer. Patients with unresectable pancreatic adenocarcinoma were treated with escalating doses of OGF for 30 min i.v. to determine the MTD. The s.c. route of administration also was evaluated. Once the MTD was established, a group of patients was treated chronically, and monitored for safety and toxicity. Hypotension was the dose-limiting toxicity, resulting in a MTD of 250 microg/kg i.v. Due to limited solubility of OGF in small volumes, a maximum dose of 50 microg/kg twice daily was determined by the s.c. route of administration. No adverse events were reported for oxygen saturation, cardiac rhythm, laboratory values or neurological status in either the acute or chronic parts of the study with the i.v. or s.c. routes. During the chronic i.v. phase, two subjects had resolution of liver metastases and one showed regression of the pancreatic tumor. Mean survival from the time of diagnosis was 8.7 months (range 2-23 months) in the i.v. group and 9.5 months (range 1-18 months) in the s.c. group. We conclude that OGF can be safely administered to patients with advanced pancreatic cancer. Further studies are needed to determine the efficacy of OGF alone or in combination with present modes of therapy for the treatment of pancreatic cancer.

PMID: 15014352

Opioid Growth Factor Improves Clinical Benefit and Survival in Patients with Advanced Pancreatic Cancer

Jill P Smith, Sandra I Bingaman, David T Mauger, Harold H Harvey, Laurence M Demers, Ian S Zagon

Departments of Medicine, Public Health Sciences, Pathology, and Neurosciences and Anatomy, Pennsylvania State University, College of Medicine, Hershey Medical Center, Hershey, PA, USA

Background: Advanced pancreatic cancer carries the poorest prognosis of all gastrointestinal malignancies. Once the tumor has spread beyond the margins of the pancreas, chemotherapy is the major treatment modality offered to patients; however, chemotherapy does not significantly improve survival.

Objective: Opioid growth factor (OGF; [Met5]-enkephalin) is a natural peptide that has been shown to inhibit growth of pancreatic cancer in cell culture and in nude mice. The purpose of this study was to evaluate the effects of OGF biotherapy on subjects with advanced pancreatic cancer who failed chemotherapy.

Methods: In a prospective phase II open-labeled clinical trial, 24 subjects who failed standard chemotherapy for advanced pancreatic cancer were treated weekly with OGF 250 μg/kg intravenously. Outcomes measured included clinical benefit, tumor response by radiographic imaging, quality of life, and survival.

Results: Clinical benefit response was experienced by 53% of OGF-treated patients compared to historical controls of 23.8% and 4.8% for gemcitabine and 5-fluorouracil (5-FU), respectively. Of the subjects surviving more than eight weeks, 62% showed either a decrease or stabilization in tumor size by computed tomography. The median survival time for OGF-treated patients was three times that of untreated patients (65.5 versus 21 days, p < 0.001). No adverse effects on hematologic or chemistry parameters were noted, and quality of life surveys suggested improvement with OGF. Limitations: Measurements other than survival were not allowed in control patients, and clinical benefit comparisons were made to historical controls.

Conclusion: OGF biotherapy improves the clinical benefit and prolongs survival in patients with pancreatic cancer by stabilizing disease or slowing progression. The effects of OGF did not adversely alter patient quality of life. The use of OGF biotherapy at earlier stages of disease or in combination with other chemotherapeutic agents may further improve the outcome of this malignancy.

Dovepress Journal, March 2010 , Volume 2010:2

Clinical Trials

In-Vitro And Preclinical Trials