Recipient Organization
AMPLE AGRICULTURE, INC.
255 RIVER ST
CAMBRIDGE,MA 02139
Performing Department
(N/A)
Non Technical Summary
This project aims to test a new class of feed additives designed to improve productivity by redirecting energy away from methane waste towards greater meat and milk production in cattle. We will evaluate AMP-202, a feed additive that employs a novel mechanism that reduces the bioavailability of nickel. Nickel is required by the rumen microbes to produce waste methane, yet there is no known nutritional requirement for nickel in ruminants themselves. Reducing the rumen concentration of nickel will inhibit methane production, allowing the animals to capture energy from feed that would otherwise be lost to methane.This project will specifically test the safety and tolerability of AMP-202 in beef cattle, and inform an understanding of its impact on methane production and average daily gain. Building on promising in vitro data that demonstrate nickel-dependent and dose-dependent inhibition ofmethanogenesis by AMP-202, this project includes three tasks:1. Proof-of-concept test for safety and efficacy in cattle2. Dose-finding to identify lowest effective dose3. Necropsy to evaluate toxicologyThe primary objective of this study is to assess safety and tolerability of AMP-202, with secondary outcomesrelated to efficacy. Promising results from this study will support a Phase 2 application to conduct a larger efficacy study.
Animal Health Component
80%
Research Effort Categories
Basic
20%
Applied
80%
Developmental
0%
Goals / Objectives
Meeting growing demand for meat and milk while ensuring continued affordability for consumers and profitability for producers will require continued improvements in productivity, including from novel mechanisms. Approximately 6% of all energy in feed is lost to animals as waste methane, energy that can potentially be redirected towards enhanced production. Because feed is the largest single cost that producers carry, reducing energy loss to methane production opens a significant economic opportunity. Ample Agriculture has developed a novel mechanism of action for improving ruminant productivity - the sequestration of nickel in the rumen. All biogenic methane is produced by a single nickel-dependent enzyme, MCR, and nickel bioavailability is nearly rate-limiting for methane production in the rumen. Ample Agriculture is developing compounds that bind and reduce the bioavailability of nickel, preventing formation of the methane producing enzyme and allowing energy that might otherwise flow to methane to be redirected towards the host. In a previous test of this nickel sequestration approach, calves treated with Ni-binding AMP-101 demonstrated improvements in average daily gain and reductions in methane production. Building on this early success with AMP-101, the present project aims to evaluate AMP-202, a second generation nickel-sequestering product designed to inhibit waste methane and improve productivity in ruminants. Major Goal:To demonstrate the feasibility and safety of AMP-202 as a strategy for shifting energy from methane production to animal productivity in beef cattle, while identifying appropriate dose levels and delivery methods for future efficacy studies.Objectives:Demonstrate the safety of AMP-202 in beef cattleCharacterize the pharmacokinetics and pharmacodynamics (PK/PD) of AMP-202Determine required washout periodAssess systemic absorption and excretion, if anyDetermine effects of AMP-202 on mineral bioavailabilityQuantify the impact of AMP-202 on enteric methane production in beef cattleEvaluate the effects of AMP-202 on average daily gain (ADG) and feed efficiencyDetermine lowest AMP-202 dose that results in 1) improved productivity, 2) reduced energy loss to methane or 3) improvement in or other measures related to energy conservation (e.g. VFA production)Confirm stability and storage properties of AMP-202 under real-world conditions
Project Methods
This project is a proof-of-concept study to evaluate the impact of AMP-202 on methane production and animal productivity in Aberdeen Angus cattle. Cattle will be randomized 1:1 between treatment and control conditions. During the first task of this study, animals in the treatment arm will receive a daily dose administered via cannula of AMP-202 to inform proof-of-concept and a safety envelope for future studies. Following a washout period, we will proceed to the second task and administer an ascending course of doses in animal feed, with a washout period between each dose. After a final washout period, in the third task, animals will be sacrificed and a necropsy will be performed.Evaluation:Animal health and safety outcomes will be assessed through a treatment-blinded, independent consulting veterinarian. Animals will be evaluated for mobility, general health and appearance, and rate of weight gain. In addition to veterinary assessment, measurements of cattle half weight and DMI will be used to assess the effects of AMP-202 on intake, gain and efficiency. Upon presentation for slaughter, cattle will be evaluated by the USDA-FSIS inspector to ensure no signs of disease or illness are present. Following processing in the UGA Meat Science and Technology Center, carcasses will be hung and broken between the 12th/13th rib, so that yield grade and quality grade can be estimated by the UGA Meats Judging Team and Faculty.AMP-202 treatment vs. control groups will be evaluated for changes in one or more of the following parameters:Average Daily GainFeed EfficiencyTrace mineral concentrationsEnteric methane production by in vivo or in vitro methodsVFA levels in vivo and production potential in vitroSigns of disease in necroscopyPower calculations: If the true effect size (δ) for any of our key outcome measures is double the standard deviation (σ), then this study will achieve a power (1-β) of >0.8 at an α level of 0.05. This study is designed to demonstrate proof-of-concept and, given the resource limitations of a Phase 1 STTR, is statistically powered to detect only large effect sizes (δ>2σ). Our expectation is that the results from this study can be used to inform the design of a more conservatively powered follow-on study.?