Accelerating Medicines Partnership® Program – Type 2 Diabetes

Identifying prioritized targets for type 2 diabetes and its complications

The Problem
Researchers studying and attempting to treat type 2 diabetes have long lacked the tools needed to identify the genes responsible for the disease and to identify and validate drug targets to treat it.
The Solution
AMP T2D established a publicly available portal to house data from millions of type 2 diabetes patients and provide analytical tools for researchers to identify genes of interest and validate drug targets.

Overview

The Accelerating Medicines Partnership® (AMP®) Program Type 2 Diabetes (AMP T2D) was a precompetitive partnership among government, industry, and nonprofit organizations that harnessed the collective capabilities, scale, and resources to improve current efforts to develop new therapies for complex heterogeneous diseases, such as diabetes and diabetic complications. 

At the time that the project launched, type 2 diabetes affected approximately 26 million people in the US and over 170 million worldwide, with the prevalence increasing rapidly.  While there were a number of approved type 2 diabetes therapies on the market, it remained a major unmet medical need, as no therapy had shown to achieve long-term reversal of the progression of hyperglycemia, or to prevent complications. Given the complex and intersecting pathways that control glucose homeostasis and energy balance, and the lack of clinical validity of existing cell and animal models, validation of drug targets for type 2 diabetes had remained challenging. 

A promising approach was to take advantage of human genetics to validate drug targets. Literature had shown that by examining variants that affect type 2 diabetes and related phenotypes, researchers could unveil relevant mechanisms and pathways to validate drug targets. Therefore, the AMP T2D project explored human genetics as an approach to validate targets by exploiting experiments in nature that perturb protein functions. 

One of the first three projects in the AMP portfolio, AMP T2D was managed by the FNIH from 2014-2021. Building on the success of AMP T2D, the initiative was expanded to investigate other common metabolic diseases through the AMP CMD project in May 2021.

Results and Accomplishments

AMP T2D exceeded the original goals of identifying prioritized targets for type 2 diabetes and its complications. It created federated nodes that enabled data from across the globe to be queried and analyzed, and developed advanced analytical tools and methods that enabled researchers to identify target genes from noncoding genetic risk variants. Additionally, the AMP T2D Knowledge Portal has become the go-to-source for researchers to deposit large amounts of diabetes and complications data for published studies (newly deposited data are curated and harmonized for querying alongside preexisting data). 

Partners

Public-Sector Partner

Private-Sector Partners

*Provided financial and/or in-kind support for this project.

FNIH Contacts

Specific project accomplishments include:

  • Amassing, integrating and harmonizing genetic and genomic data from over 1.5 million individuals and making the data publicly accessible for querying.
  • Connecting data from over 230 phenotypes related to type 2 diabetes and metabolic complications and generating new genomic and target annotation data.
  • Compiling 271 unique datasets into a single resource, which included data on 330 different traits relevant to type 2 diabetes by the close of the AMP T2D project.

Scientific Publications

Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controlsNature

Media

NIH News Release (June 10, 2016): Diabetes Portal adds data, more powerful search tools

NIH News Release (October 7, 2015): International diabetes research knowledge portal opens to public, scientists

FNIH Press Release (February 26, 2015): Accelerating Medicines Partnership Announces Awards to Advance Research in Type 2 Diabetes

ACCELERATING MEDICINES PARTNERSHIP and AMP are registered service marks of the U.S. Department of Health and Human Services.