Biotec Pharmacon has since late 1980’s performed basic research on the mode of action of the beta-1,3/1,6-glucan. The early work dating back to the mid-1980’s were focused on characterization of beta-glucans from yeast combined with structure/function relationship studies especially in aquatic animals and was a spin off from research initiated at the University of Tromsø. This early work was followed by a number of studies in warm blooded animals, and later also in man. The company’s own basic research, combined with the intensified interest in the scientific community to understand innate immune mechanisms governed by beta-glucans, has been a solid foundation for the current understanding of its mode of action. Experience over a this 20/30 years period has confirmed that Biotec Pharmacon’s specific yeast beta-1,3/1,6-glucans can enhance overall disease resistance and improves health, and furthermore that their pure beta-1,3/1,6-glucans are non-toxic modulators that can affect a number of immunity related disorders.
Biotec Pharmacon was for two decades (until 2008) the leading producer of immunomodulatory beta-1,3/1,6-glucan products for animal husbandry and veterinary medicine, and was also heavily involved in a number of basic research projects within this area from which a number of scientific papers has been published (1-15). The portfolio of products for this marked segment was divested in 2008 to a Brazilian company. As from 2014 Biotec BetaGlucans has re-entered this segment and is now supplying beta-1,3/1,6-glucan products for aquaculture.
Biotec Pharmacon has also undertaken research related to the use of beta-glucans as consumer products both as dietary supplements and cosmetics, from which a number of papers and patents have been published. The sale within this marked segment was divested from the company in late 2009 and is today marketed by the company NutraQ or Immunocorp, but where Biotec BetaGlucans still is the producer of all the beta-glucan ingredients.
The present research focus is the company’s proprietary soluble yeast beta-glucan for the application within treatment of wounds, especially chronic slow healing wounds like diabetic ulcers. The company is also developing beta-glucan products that can aid in cancer treatment as adjuvant in combination with antibodies or vaccines, and has also performed research on the ability of beta-glucans to assist in enhancing the efficacy of mucosal influenza vaccines. Much of the basic early work on the potential use of beta-glucans in medicine were performed by a handful pioneer groups within innate immunity in Japan, Norway, and USA.
The company has established close collaboration with a number of leading research groups both in Norway, Europe and in USA and a number of research projects have been executed in collaboration with external research groups. These projects have lead to novel insight both for the potential use of beta-glucans as well as mode of action (16-22).
A major complication occurring in people with diabetes is the development of hard to heal ulcers that often become chronic. It is postulated that both the lack of nerve signaling (neuropathy) as well as dysfunctional macrophages are major contributors to the impaired wound healing. Since beta-glucans are known to activate macrophages the company started out early doing research on how their beta-glucans could affect diabetic macrophage functions and thus its possible use in treating diabetic ulcers. The company has performed a number of both in vitro studies as well as animal model studies to better understand the mechanism of action and to find formulations that would be optimal as wound healing products. This is currently the main focus of the company’s research program.
Since 2003 Biotec Pharmacon ASA has collaborated with scientists at Memorial Sloan Kettering Cancer Center on the use of soluble beta-glucan in treatment of cancer in combination with monoclonal antibodies and vaccines. The work has resulted in a series of patents and patent application protecting this combination treatment to which Biotec Pharmacon has co-ownership to or exclusive license from MSKCC. A number of papers have also been published as outcome of the collaboration with Charite Unversitätsmedizin Berlin (20-22).
Inflammatory Bowel Disease
Biotec Pharmacon has since long had research collaboration with the immunology group at Laboratory for Immunohistochemistry and Immunopathology at the National Hospital in Oslo. The collaboration has both lead to novel insight into the mode of action of beta-glucans when administered to mucosal surfaces, as well a new IP on the potential use of Soluble Beta-Glucan in treatment inflammatory bowel disease(23).
Asthma and Allergy
Since beta-glucans are known to be potent immunomodulators where regulation of immune responses is an established outcome of using beta-glucans in model systems, a joint project together with Mount Sinai School of Medicine was established on the potential use of beta-glucans is asthma therapy. In a series of experiments it was demonstrated that the Biotec Pharmacon beta-glucans could protect against development of asthma in an animal model.
- Engstad, R. and Raa, J. Immune-stimulation improving health and performance. Feed Magazine (Kraftfutter) 7-8, 261-266. 1999.
- Engstad RE, Robertsen B. Effect of structurally different b-glucans on immune responses in Atlantic salmon (Salmo salar L.). Journal of Marine Biotechnology 1995;3:203-7.
- Engstad RE. Yeast b-glucan as an immunostimulant in Atlantic salmon (Salmo salar L.): Biological effects, recognition and structural aspects. Tromsø: University of Tromsø, 1994.
- Engstad RE, Robertsen B. Specificity of a b-glucan receptor on macrophages from Atlantic salmon (Salmo salar L.). Developmental and Comparative Immunology 1994;18:397-408.
- Engstad RE, Robertsen B. Recognition of yeast cell wall glucan by Atlantic salmon (Salmo salar L.) macrophages. Developmental and Comparative Immunology 1993;17:319-30.
- Engstad RE, Robertsen B, Frivold E. Yeast glucan induces increase in lysozyme and complement-mediated haemolytic activity in Atlantic salmon blood. Fish and Shellfish Immunology 1992;2:287-97.
- Engstad RE, Tveite S, Riesen G. Differentiation of yeast cell wall components related to their immune-stimulation properties. Tierernärung – Ressourcen und neue Aufgaben;Hannover: Landbauforschung Völkenrode, 2001:407-13.
- Engstad RE, Riesen G. Beta-glucan as immunostimulant: Biological effects, recognition and structural aspects. In: Schubert R, Flachowsky G, Jahreis G, Bitsch R, editors. Vitaminen und Zusatzstoffe in der Ernährung von Mensch und Tier; 2001 Sep 26; Jena, Germany: Friedrich-Schiller-University, 2001:443-6.
- Engstad RE, Lunde H, Robertsen B. Effect of soluble versus particulate yeast beta-glucan (MacroGard) on immune responses in Atlantic salmon. In: Gudding R, Lillehaug A, Midtlyng PJ, Brown F, editors. Development in Biological Standardization; Karger, 1997:463.
- Paulsen SM, Engstad RE, Robertsen B. Enhanced lysozyme production in Atlantic salmon (Salmo salar L.) macrophages treated with yeast beta-glucan and bacterial lipopolysaccharide. Fish Shellfish Immunol 2001;11(1):23-37.
- Paulsen SM, Lunde H, Engstad RE, Robertsen B. In vivo effects of b-glucan and LPS on regulation of lysozyme activity and mRNA expression in Atlantic salmon (Salmo salar L.). Fish & Shellfish Immunology 2003;14:39-54.
- Raa J, Roerstad G, Engstad R, Robertsen B. The use of immunostimulants to increase the resistance of aquatic organisms to microbial infections. In: Shariff IM, Subasinghe RP, Arthur JR, editors. Diseases in Asian Aquaculture II. Manila, Philipines: Fish Health Section, Asian Fisheries Society, 1992:39-50.
- Raa, J., Engstad, R. E., and Tveite, S. Beta-1,3/1,6-glucans. Modern science and ancient wisdom combined for the benefit of aquaculture. I Dybden . 2001.
- Robertsen B, Engstad RE, Jørgensen JB. b-glucans as immunostimulants in fish. In: Stolen JS, Fletcher TC, editors. Modulators of Fish Immune Responses. Fair Haven, NJ: SOS Publications, 1994:83-99.
- Robertsen B, Rørstad G, Engstad R, Raa J. Enhancement of non-specific disease resistance in Atlantic salmon, Salmo salar L., by a glucan from Saccharomyces cerevisiae cell walls. Journal of Fish Diseases 1990;13:391-400.
- Preus HR, Aass AM, Hansen BF, Moe B, Gjermo P. A randomized, single-blind, parallel-group clinical study to evaluate the effect of soluble beta-1,3/1,6-glucan on experimental gingivitis in man. J Clin Periodontol 2008;35(3):236-41.
- Lehne G, Haneberg B, Gaustad P, Johansen PW, Preus H, Abrahamsen TG. Oral administration of a new soluble branched beta-1,3-D-glucan is well tolerated and can lead to increased salivary concentrations of immunoglobulin A in healthy volunteers. Clin Exp Immunol 2006;143(1):65-9.
- Breivik T, Opstad PK, Engstad R, Gundersen G, Gjermo P, Preus H. Soluble beta-1,3/1,6-glucan from yeast inhibits experimental periodontal disease in Wistar rats. J Clinical Periodontology 2005;32:347-3.
- Ragupathi G, Yeung KS, Leung PC, Lee M, Lau CB, Vickers A, Hood C, Deng G, Cheung NK, Cassileth B, Livingston P. Evaluation of widely consumed botanicals as immunological adjuvants. Vaccine 2008;26(37):4860-5.
- Harnack U, Eckert K, Fichtner I, Pecher G. Oral administration of a soluble 1-3, 1-6 beta-glucan during prophylactic survivin peptide vaccination diminishes growth of a B cell lymphoma in mice. Int Immunopharmacol 2009;9(11):1298-303.
- Harnack U, Eckert K, Fichtner I, Pecher G. Comparison of the effect of orally administered soluble beta-(1-3),(1-6)-D-glucan and of G-CSF on the recovery of murine hematopoiesis. In Vivo 2010;24(1):59-63.
- Harnack U, Johnen H, Pecher G. IL-1 receptor antagonist anakinra enhances tumour growth inhibition in mice receiving peptide vaccination and beta-(1-3),(1-6)-D-glucan. Anticancer Res 2010;30(10):3959-65.
- Sandvik, A. A study on immunomodulating beta-glucan: Effects of oral application on inflammation, tissue injury, and the mucosal immune system in experimental animals. 1-78. 15-4-2009. University of Oslo.