On February 6, the NIH announced the Accelerating Medicines Partnership (AMP), a collaboration among the agency, 10 pharmaceutical companies, seven nonprofit organizations and one trade group, the Pharmaceutical Research and Manufacturers of America (PhRMA). The program will be funded with more than $230 million over five years and will focus on three main areas: Alzheimer’s disease (AD), type II diabetes (T2D), and autoimmune diseases rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). These are pilot projects that are hoped to set the path to expand the partnership to other diseases. Data and analyses will be shared publicly.

The advent and advancement of techniques in areas such as next generation sequencing, informatics and single-cell analysis have furthered understanding of the factors involved in disease development and progression. “Recent research, including the use of state-of-the art technologies, has indeed increased the identification of potential drug targets and biomarkers. However, it is the translation of these observations into validated entities that has been limited. Hence, the importance of AMP, which emphasizes the roles of patients and patient-derived biological samples in this process,” explained William Chin, MD, executive vice president, Scientific and Regulatory Affairs of PhRMA. AMP presents an opportunity to incorporate these technologies into new approaches to disease research. AMP’s members will share in planning, costs and resources, and will take advantage of the ongoing development of new technologies to increase the numbers of biomarkers for these diseases and more efficiently identify and validate drug targets. The approaches to achieving this for each disease area differ, given the current state of research and data available for each. Consequently, techniques to be used vary as well. As Dr. Chin specified, “The new technologies include novel imaging approaches in Alzheimer’s and single-cell white blood cell analyses in autoimmune diseases.”

AMP’s approach to AD research will address the lack of data from clinical trials. According to Suzana Petanceska, PhD, program director of the National Institute on Aging Division of Neuroscience, AMP will use network and systems biology to develop targets. “Three multi-institutional academic groups funded by the NIH will apply innovative analytical methods to large-scale molecular, cellular and clinical data from Alzheimer’s patients to gain new insights into the complex biology of the disease, identify potential therapeutic targets for all stages of AD and characterize the molecular networks in which they operate,“ she stated. Brains of over 2,500 patients at all stages of AD or with other neurodegenerative diseases will be analyzed, and new proteomic, whole genome sequencing and RNA-seq data, and analyses of DNA methylation and miRNA will be combined with existing data. Network models developed to pinpoint important factors in development of AD will be validated in multiple model systems. “This phase of the projects will include actual or in silico high-throughput screening for novel compounds or drugs already in use for other conditions that possess the ability to therapeutically modulate the putative targets,” stated Dr. Petanceska.

By contrast, a wealth of data has been collected from a wide range of T2D patients and those at risk of developing the disease, and AMP will prioritize building a knowledge portal of these data. According to Phillip Smith, PhD, deputy director of the National Institute of Diabetes and Digestive and Kidney (NIDDK) Diseases Division of Diabetes, Endocrinology and Metabolic Diseases, and codirector of the NIDDK Office of Obesity Research, the individual datasets from the different AMP partners have been too small to support thorough analysis of the data but now will be publicly available to be combined. During the course of the project, investigators will develop the tools to allow them to identify meaningful associations across the different types of available data (e.g., genetic, clinical and experimental). They plan to deep sequence areas identified through these associations as potentially useful in revealing important disease-related pathways.

Data from the Illuminating Druggable Genome project, which works to increase the number of known proteins in the genome to bind drugs, will assist in selecting targets for drug development. Information from the NIH Encyclopedia of DNA Elements, which works to understand the functional elements of the human genome, and the Common Fund Epigenomics Programs, which studies the regulation of gene activity that does not involve DNA sequence, will be used to link noncoding genetic variation with regulation of gene networks. As Dr. Smith stated, “The main innovations are in the free access to the public of the first database with sufficient numbers of individuals with both genetic and phenotypic data to identify novel pathways involved in the development of diabetes in humans, and the partnership between academia and industry to develop analytical tools to validate promising drug targets in humans prior to launching extensive and expensive drug development programs.”

Employing yet another approach, AMP plans for both SLE and RA research to emphasizes single- and group-cell analyses to develop targeted therapies for patients of the two diseases. According to Gary Gilkeson, MD, chair of the Lupus Foundation of America Medical—Scientific Advisory Council and associate dean of the Medical University of South Carolina, some of the most valuable technologies for lupus research thus far include microarray analysis, metabolomic and advanced flow cytometry techniques, and analysis techniques that have identified genetic links to SLE. Resource-sharing approaches planned by AMP include proteomics, metabolomics, lipidomics and single-cell RNA-seq. “One emphasis is doing this on tissue in addition to peripheral blood,” he explained.

Robert Carter, MD, deputy director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, indicated that mRNA analysis and flow cytometry are among the single-cell analysis techniques to be applied to disease-affected tissue of RA and SLE patients as part of AMP. Epigenetic analysis in particular may be valuable in developing targeted drug therapies for the autoimmune diseases. Currently, a few hundred cells are required to measure all of a given type of epigenetic change across the entire genome, but Dr. Carter expects new techniques in this area to develop during the course of AMP that will allow such analysis of individual cells. Regarding new capabilities from these techniques, “a wish list would include analyses of all the metabolites within a cell, or all of the activated proteins,” he stated.