Agmaset and AgmaVet TM

Transcription

1 Agmaset and AgmaVet TM Science Leading to Product Agmaset and AgmaVet TM - Nutraceuticals containing the neuroprotective ingredient G-Agmatine. G-Agmatine - Gilad&Gilad s trademarked brand of agmatine. Neuroscientists Donated to Dr. Donald J. Reis s Laboratory of Neurobiology, Cornell University Medical College. (oil pastel on paper)

2 Agmatine* A Novel Neuroprotective Dietary Ingredient** *Discovered in 1910 (Albrecht Kossel) **Neuroprotection Discovery 1995 (Gilad et al.) Chemical Formula H 2 N-C-NH-(CH 2 ) 4 -NH 2 NH Structural Formula

3 Metabolic Pathways -Agmatine is a metabolite of the amino acid arginine- -But agmatine exerts different effects than arginine- Adapted from Halaris and Plietz (CNS Drugs 21, , 2007) Arginine Arginine Decarboxylation NO Synthase Agmatine Ornithine Decarboxylase Agmatine Agmatinase Diamine Oxidase Polyamines

4 Agmatine is a Naturally Occurring Compound with Broad Distribution in the Body Brain: Blood: 300 ng/mg 47 ng/ml Intestine: 55 ng/mg Fecal: 3,290 ng/g

5 Agmatine is a Ubiquitous Compound Present in Many Plant- and Animal-Derived Foodstuff Commonly found in foodstuff derived from plants, fish and animals (usual range: mg/kg). High levels are found in certain fish products (200 and up to 650 mg/kg). Intestinal microbial production is considered a major source of agmatine.

6 Agmatine Exerts Multiple Effects -Animal Model Experiments- Neuroprotection. Healthy pain-free nerve functions. Healthy mood functions. Healthy coping with Stress. Learning and memory enhancement. Healthy blood glucose regulation. Healthy blood flow. Protection of healthy kidney functions. Healthy control of cell growth.

7 A Unique Mechanism of Action The Molecular Shotgun Concept NMDA IR Ion Channels PAs Insulin & Glucose AGEs Agmatine Modulates Multiple Molecular Targets

8 Translating Research into Practice

9 Absorption, Distribution, Metabolism and Elimination Oral agmatine is absorbed by the gastrointestinal tract. Agmatine is distributed throughout the body. It crosses the blood-brain-barrier. Agmatine is mostly converted to putrescine, precursor for polyamine synthesis, and urea. Some may be oxidized. Agmatine is excreted by the kidneys.

10 Agmatine in Urine Following Oral Intake (2 hr apparent blood half-life) Arbitrary Units (AU) Measured by ELISA Adapted from Huisman et al. (Anal. Chem. 82, , 2010)

11 Translation of Research into Treatment -Clinical Studies Focus on Sciatic Nerve- sciatic nerve Adapted from WebMD Slideshow: A Visual Guide to Sciatica

12 Safety Clinical Trial -Open Label, Dose-Escalating Clinical Study Design- Keynan et al., Pain Med., 2010;11(3): Cohort 1 st Cohort 2 nd Cohort 3 rd Cohort 4 th Cohort Participants [Male] [Female] 5 [3] [2] 5 [1] [4] 12 [7] [5] 12 [8] [4] Treatment Regimen 1 capsule 3 times daily (1.335 g agmatine sulfate/day) - 10 day treatment 2 capsules 3 times daily (2.670 g/day) - 10 day treatment 8 daily capsules (2 in the morning, 3 at noontime and 3 in the evening) (3.560 g/day) - 10 day treatment 8 daily capsules (2 in the morning, 3 at noontime and 3 in the evening) (3.560 g/day) - 21 day treatment Adverse Effects During 7 month Follow-up 1 st Cohort 2 nd Cohort 3 rd Cohort 4 th Cohort Mild Diarrhea 1 2 Discontinuations Due to the above Adverse Effects Free Will Discontinuations 1 1

13 Clinical Studies About 1.5% of the population cope everyday with circumstances that challenge healthy sciatic nerve functions. Sciatic nerve functions can be clearly defined and measured. Nerve Root Lumbar Disc

14 Efficacy Study Sciatic Nerve Functions Randomized, Double-Blind, Placebo-Controlled Trial (RCT) Keynan et al., Pain Med., 2010;11(3): Study Design g/day G-agmatine Randomization Screening Treatment Follow-up 2-5 days 14 days 61 days Day 1 Clinical Assessment (days) (Screening) (15-20) (45) (75)

15 Baseline Demographics and Clinical Data Keynan et al., Pain Med., 2010;11(3): Copyright 2017, Gilad&Gilad LLC, All rights reserved Category Age (years) * Range Gender * Female Male Group. Placebo (n = 30) GVG-1 (n = 31) 44.8± (46.7 %) 16 (53.3 %) 44.1± (41.9 %) 18 (58.1 %) Body Mass Index () * 25.4± ±5.6 Current Smoking * 7 (25.9 %) 6 (20.7 %) Symptom Duration (weeks) * Range Herniation Level * L3 4 L4 5 L5 S1 L3 4 + L5 S1 L4 5 + L5 S1 Herniation Type * Protrusion Extrusion Protrusion + Extrusion Pain Location * Back Pain Only Back + Leg pain Pain Measures * Visual Analogue Scale McGill Pain Questionnaire Oswestry Disability Index Quality of Life Assessment SF-36 Score * Total Score Physical Health Score Mental Health Score Neurological Functions Deficits Sensory Unilateral Decrease Motor (Force/Reflex) Unilateral Weakness 7.9± (6.7 %) 13 (43.3 %) 14 (46.7 %) 1 (3.3 %) 2 (6.7 %) 27 (90.0 %) 1 (3.3 %) 3 (10.0 %) 27 (90.0 %) 6.5± ± ± ± ± ± (23.3 %) 16 (53.3 %) 11.7± (9.7 %) 10 (32.3 %) 11 (35.5 %) 2 (6.4 %) 5 (16.1 %) 1 (3.2 %) 23 (74.2 %) 7 (22.6 %) 1 (3.2 %) 30 (96.8 %) 6.9± ± ± ± ± ± (64.5 %) 25 (80.6 %)

16 VAS Score SF-36 Total Score * VAS Agmatine VAS Placebo Pain Efficacy of G-Agmatine Quality of Life ** SF-36 Placebo SF-36 Agmatine 0 -Treatment- Baseline Time Interval (Days) 0 -Treatment- Baseline Time Interval (Days)

17 Proof-of-concept The clinical studies serve a Proof-of-concept indicating the beneficial use of G-agmatine in harsh circumstances that challenge healthy nerve functions.

18 Addressed Conditions More than 20 million people in the United States alone cope everyday with circumstances that challenge healthy nerve functions

19 Recommended Effective Regimen 2 to 3 capsules twice a day with or after meals for as-long-as needed (each capsule contains 445mg of G-Agmatine ). Time to effect - - In acute circumstances: 2-4 days in most, but may be as-long-as 2 to 4 weeks. - Chronic conditions: 3-6 weeks. After the effect is established dosage may be gradually reduced for maintenance regimen.

20 AgmaSet First-of-its-Kind Dietary Supplement Containing G-Agmatine For Nervous System Health and Proper Nerve Functions Copyright , Gilad&Gilad LLC, LLC, All All rights rights reserved

21 AgmaVet TM For Your Animal's Daily Diet Containing G-Agmatine For Nerve Health

22 Safety of AgmaSet (Neurofencine TM ) Ongoing surveillance of people who take AgmaSet -No adverse effects were reported since surveillance began in May rarely cause soft stool or mild diarrhea.

23 Agmatine Sulfate Alternative Products All alternative products containing agmatine sulfate are based on borrowed science. All clinical studies are borrowed from Gilad&Gilad. Products targeting the bodybuilding field are all touted based on scientifically unsubstantiated claims and often on downright erroneous scientific information. No evidence for enhanced Growth Hormone functions. Agmatine may modulate Nitric Oxide (NO) synthesis, but does not enhance NO content. No evidence for enhanced muscle protein synthesis.

24 THANK YOU! PLEASE SPREAD THE GOOD NEWS Any Questions? Call us: (toll-free) , or Contact us via