Company Overview. How Powering the Immune System Can Benefit Athletic Performance. March 2013

Transcription

1 How Powering the Immune System Can Benefit Athletic Performance March 2013 Company Overview Privately held Minnesota biotechnology company founded in Technology platform focused on the innate immune system. 40+ U.S. patents and patents pending, plus filings in more than 20 countries. Two business units: Healthcare Group is focused on protection, providing branded foodgrade immune enhancing ingredients to the food, beverage, supplement, animal nutrition and cosmetic markets. Pharmaceutical Group is developing injectable immunotherapy drugs with a primary focus in cancer. 1

2 Acute effects of exercise on immunity Circulating immune cell numbers and functions are temporarily altered following a prolonged bout of heavy exercise Increased numbers of leukocytes (neutrophils & monocytes but fewer lymphocytes & NK cells) Increased plasma concentrations of inflammatory cytokines (TNF, IL-1, IL-6), anti-inflammatory cytokines (IL-1ra, IL-10) and positive acute phase proteins Decreased functional responses of neutrophils, NK cells, APCs, T cells, B cells etc. Acute exercise: Circulating leukocytes 2.5 to 3 hours of intensive running (n = 62 marathon runners) Nieman (1997) J. Appl. Physiol. 82,

3 Acute exercise: Phagocytosis and oxidative burst 2.5 hours of intensive running (n = 30 marathon runners) Nieman (1997) J. Appl. Physiol. 82, Acute exercise: NK cell activity Impairment may last for days 2.5 hours of intensive running (n = 62 marathon runners & n = 10 resting controls) Nieman (1997) J. Appl. Physiol. 82,

4 # of NK cells drops => decreased activity mirrors the fall in number (activity per NK cell not altered?) Impairment may last for days 2.5 hours of intensive running (n = 62 marathon runners & n = 10 resting controls) Nieman (1997) J. Appl. Physiol. 82, Acute exercise: T cell proliferation May reflect decreased circulating # of T cells 2.5 hours of intensive running (n = 22 marathon runners vs. n = 10 resting controls) Nieman (1997) J. Appl. Physiol. 82,

5 Acute exercise: Secretory IgA Nasal IgA decreased by up to 70% for up to 18 hr after a 31 km run Salivary IgA declined following 2 to 3 hr of exhaustive ski competition in elite crosscountry skiers Salivary IgA declined after 2 hr of hard exercise in cyclists Low salivary IgA preceded URTI in elite squash and hockey players Exercise Stress/Biomarker Study Many immune biomarkers show a quick drop that lasts for 2-6 hours following exercise ( open window effect ). Study model developed at University of Houston Department of Health and Human Performance. 60 recreationally fit subjects/29 male, 31 female (23± 5 yr.) Cross over design, double blind, randomized Cycling at 100F for approximately one hour (two sessions) Blood and saliva samples at day zero (baseline), day 10 (pre-exercise) and post-exercise and 2 hours post-exercise Br J Nutr May 10:1-9. 5

6 Exercise Stress/Biomarker Study Healthy Zone Wellmune WGP Challenge zone Placebo Exercise Stress/Biomarker Study Biomarker data supports athletic performance benefits 1. Maintains White Blood Cell Levels. Wellmune prevented the drop in protective white blood cells that can occur following intense exercise. 2. Improved Mucosal Immunity. Higher salivary IgA, a protective protein, is associated with improved immune protection of the mucosal. Wellmune helped salivary IgA levels rebound more quickly after exercise. 3. Enhanced Immune Responses to a Simulated Challenge. The Wellmune group had higher levels of key cytokines following Lipopolysaccharide (LPS) stimulation. Br J Nutr May 10:1-9. 6

7 Key Immune Cells: Monocytes Total Monocyte Concentration Total Monocytes X 10 3 / ml * *Significantly p< 0.05 Placebo Wellmune WGP Baseline Pre Post 2h Wellmune significantly reduced the effect of exercise on circulating monocytes. Mucosal Immunity Salivary IgA Salivary IgA (pg/ml) Baseline Pre Post 2h *Significantly p< 0.05 * Placebo WGP Wellmune improved salivary IgA recovery at two hours post-exercise. 7

8 LPS-Stimulated Cytokines LPS Stimulated Cytokines : IL * IL-4 (pg / ml) * * Baseline Pre Post 2h *Significantly p< 0.05 The change demonstrates Wellmune s ability to enhance immune responses to a perceived challenge. Summary of exercise & the immune system Neutrophilia and lymphopenia Increased (blood) neutrophil and monocyte phagocytosis Decreased NK cell activity Decreased T cell response Decreased secretory IgA Maintained humoral responses (B cell driven) Increased circulating pro- and anti-inflammatory cytokines 8

9 Why is nutrition important? Resting immune system Activated immune system Increased demand for energy and for building blocks (cells, proteins etc.) Nutrients can also be: Precursors of mediators involved in the immune response - Arginine & NO - Arachidonic acid and eicosanoids Regulators of mediator production Regulators of signal transduction & gene expression in immune cells (& so of cellular responses) - Many micronutrients Components of protection system against immune damage to the host - Antioxidants 9

10 Nutritional/non-nutritional approaches Carbohydrate Glutamine Antioxidant vitamins Trace elements (zinc) Omega-3 fatty acids Yeast beta-glucan Probiotics & prebiotics Others Glutamine Rationale: fuel for immune cells; maintains optimal immune function in vitro; beneficial in post-surgery, burns and critical illness; blood concentration declines with exercise Limited effect on exercise-induced alterations in immune function when consumed during or after exercise One study reported lower URTI in marathon runners who consumed glutamine 10

11 Zinc Rationale: Essential for immune function; component of antioxidant defence system (SOD); lost in sweat Limited evaluation in the context of exercise High doses impair immune function: exerciseinduced reduction in T cell function exaggerated by 50 mg Zn + 3 mg Cu/day for 6 days Probiotics Rationale: live bacteria that interact with host gut epithelia and immune system In elite distance runners L. fermentum for 28 days decreased risk and severity of respiratory illness and enhanced some immune parameters L. acidophilus for one month prevented exerciseinduced impairment of T cell function L. casei for one month partly prevented exerciseinduced decline in NK cell activity L. rhamnosus GG for 3 months reduced the duration of GI-symptoms during marathon training and in the 2 weeks following a marathon L. casei maintained salivary IgA and lowered incidence of URTI over 4 months in university athletes 11

12 Yeast Beta-glucan as a dietary intervention: Wellmune Science & Technology Wellmune WGP Source Proprietary Strain of Yeast (Saccharomyces Cerevisiae) Yeast Cell Mannoprotein Beta 1,3/1,6 Glucan Beta 1,3/1,6 Glucan Lipids, Proteins, Nucleic Acids and cellular contents Yeast Cell Cross Section Fibrillar Layer Mannoprotein Beta 1,3/1,6 Glucan Mannoprotein Plasma Membrane Cytoplasm. Lipids 12

13 Technology Background Immunology Discoveries Dr. Gordon Ross, Brown Cancer Center Deputy Editor-Journal of Immunology Dr. Ross s research in the 1980s: How does the body clear a yeast or fungal infection? Neutrophil responsible for killing yeast and fungal challenges. Specific receptor (Complement Receptor 3 or CR3) on the surface of neutrophils that triggered killing. CR3 requires a specific carbohydrate and complement to initiate killing. Immune Response to Yeast / Fungus Yeast or Fungus ic3b 1. Natural antibody binds to yeast and activates complement 2. Complement (ic3b) binds (fixes) to target yeast and attracts immune cells Complement Receptor 3 ic3b ic3b β1,3/1,6 Glucan 3. Neutrophil binds to the complement (via CR3) and to the β1,3/1,6 Glucan on the surface of the yeast at the same time which triggers a CR3-mediated killing mechanism. Neutrophil 13

14 Wellmune WGP Priming of Neutrophils Wellmune WGP binds to CR3 on neutrophil priming the immune cell for activity Neutrophil Wellmune WGP Priming of Neutrophils Target: Foreign Challenge ic3b ic3b ic3b 4. Primed neutrophil binds to complement on target via CR3 which activates CR3-mediated killing mechanism. Primed Neutrophil 14

15 How Wellmune WGP Works 1) Taken orally, Wellmune WGP is taken up into the body via the Peyer s Patches in the intestines. 2) Immune cells called macrophages containing Wellmune WGP travel to the immune organs throughout the body. 3) Macrophages break down Wellmune WGP into smaller fragments that bind to neutrophils, the most abundant immune cell in the body. 4) Neutrophils more quickly recognize and kill foreign challenges. Hong et al. (2004) J. Immunol. 173, Clinical Research 15

16 Biothera Healthcare Clinical Research Study Name Presented Published 1) Texas Marathon** 2012 American Soc. of Sports Medicine Accepted J. of Dietary Supplements 2) Exercise Stress* 3) Medical Students* 4) Lifestyle Stress 90-day* 5) Lifestyle Stress 28-day* 2011 Int l Society of Exercise Immunology British Journal of Nutrition, British Society of Immunology Nutrition, Experimental Biology J. of American College of Nutrition, American College of Nutrition Agro Foods Industry Hi Tech, ) Allergy* 2011 Experimental Biology Food Science & Nutrition, ) California Marathon* 8) Cold/Flu* 9) Firefighters 2007 American College of Nutrition J. of Sports Science & Medicine, Experimental Biology Journal of Applied Research, American Soc. of Sports Medicine Manuscript in preparation *Published **Accepted for publication Wellmune WGP Human Study Dosage Study 1) Texas Marathon 2) Exercise Stress 3) Medical Students 4) Lifestyle Stress 90-day 5) Lifestyle Stress 28-day Wellmune Serving (dose) 250 mg 250 mg 250 mg 250 mg 250 mg, 500 mg 6) Allergy 250 mg 7) California Marathon 8) Cold/Flu 9) Firefighters 250 mg, 500 mg 500 mg 250 mg 16

17 Texas Marathon Stress Study Study Protocol Research conducted by the Health and Human Performance Lab, University of Houston 182 subjects completed the 2011 Austin TX Marathon Double-blinded, placebo-controlled 250 mg for four weeks post-race ü Wellmune Soluble and Wellmune Dispersible groups Health questionnaire focusing on (1) upper respiratory tract infection (URTI) symptoms & (2) daily health log of overall physical health Baker s Yeast Beta Glucan Supplementation Reduces the Number of Cold/Flu Symptomatic Days After Completing a Marathon. Presented to the American College of Sports Medicine, San Francisco, CA. #1: 2011 Texas Marathon Stress Study 10.0# Average'Symptom'Days'per'Subject' Average'Days'with'Symptoms' 9.0# 8.0# 7.0# 6.0# 5.0# 4.0# 3.0# 2.0# 1.0# 0.0# * Wellmune'Dispersible' Placebo' Wellmune'Soluble' Overall: >34% Reduction in URTI Symptoms vs Control * p<0.05% Data presented to the 2012 Am College of Sports Med, San Francisco, CA. Dr. Brian McFarlin, U of North Texas, Department of Exercise Physiology & Nutrition. 17

18 Stress Study - Firefighters Firefighters Study Protocol Study design - impact of Wellmune WGP on URTI in fire crews fighting wildfires. 54 subjects. Crossover design, single blind, one crew on Wellmune WGP for 2 weeks, other on placebo; switch groups during rest period (3-5 day rest). Primary endpoint URTI incidence. Secondary endpoint overall health. Study co-funded by US Air Force and conducted by University of Montana. Presented: American College of Sports Medicine, May Publication pending. Stress Study - Firefighters Study Results Wellmune WGP reduced by 23% the incidence of URTI (p=0.06) Wellmune WGP dramatically improved overall physical health (p=0.006) Subjects reported supplement increased feeling of overall wellness Trend toward increased work output Presented at 2008 American College of Sports Medicine Conference, May 28-31,

19 Summary ü Intensive exercise affects blood immune cells, plasma cytokines, APC, T and NK cell function, secretory IgA. ü Allows us to study effects of physical stress on immune system and health. ü Maintaining immune health is an unmet need of many well-designed training programs. ü Wellmune WGP is natural and clinically proven to help athletes maintain immunity despite rigorous training. Discussion 19