Novel Target Identification Technologies for the Personalised Therapy of Type II Diabetes and Obesity

Author(s): Gunter Muller.

Journal Name: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization)

Volume 12 , Issue 3 , 2012

Submit Manuscript
Submit Proposal

Abstract:

It is well-known that the drug discovery and development process is lengthy, expensive and prone to failure. This high failure rate is a significant factor in the pharma industry’s productivity problems, subsequent mergers and downsizing. Starting from the selection of a novel target in the discovery stage, through the multiple stages of development to regulatory approval, the overall probability of success is less than 1%. Given the time and resources needed to investigate a novel biological mechanism, i.e. one that has not been tested in humans before, success rates as low as these yield an unsustainable business model. In the face of a negative return-on-investment for new chemical entity drug discovery and development and constricted healthcare budgets that demand improved drugs to warrant reimbursement, an alternative approach must be identified to provide patients with new and better therapies as well as sustain the industry. The therapy of type II diabetes and obesity is currently based on seven approved drug classes encompassing both small molecule chemicals (metformin, sulfonylureas, glitazones, DPP-IV inhibitors, pancreatic lipase inhibitors) and (unmodified or modified) proteins (insulin and analogues, glucagon-like polypeptide-I and analogues). Clearly, this repertoire does not meet the requirements for the individualized treatment of metabolic diseases with estimated 2000 to 3000 susceptibility and protective genes and even higher numbers of underlying polymorphisms and combinations thereof, that is thought to form the basis for personalised therapy in the future. As a consequence, novel strategies for the identification of targets that can be addressed by the oral delivery as well as tissue and intracellular targeting of therapeutic proteins and nucleic acids are required. The identified and validated targets emerging will hopefully enable the future development of personalised polypharmacy based on multiple and individual combinations of susceptibility gene products that contribute to the common complex metabolic diseases.

Keywords: Antidiabetic drugs, biologicals, cell reprogramming, complex diseases, exosomes, gene therapy, genetic prediction, glycosylphosphatidylinositol-anchored proteins, metabolic diseases, microvesicles, oral therapy, nanoparticles, regenerative medicine, tissue engineering, tissue targeting

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 12
ISSUE: 3
Year: 2012
Page: [183 - 207]
Pages: 25
DOI: 10.2174/187152212802001866
Price: $58

Article Metrics

PDF: 13