Affordable Access

Strategies for skeletal muscle targeting in drug discovery.

Authors
  • Ebner, David C
  • Bialek, Peter
  • El-Kattan, Ayman F
  • Ambler, Catherine M
  • Tu, Meihua1
  • 1 Pfizer Worldwide Research and Development, 610 Main St, Cambridge, MA 02139, USA. [email protected]
Type
Published Article
Journal
Current pharmaceutical design
Publication Date
Jan 01, 2015
Volume
21
Issue
10
Pages
1327–1336
Identifiers
PMID: 25269560
Source
Medline
License
Unknown

Abstract

The targeting of drugs to skeletal muscle is an emerging area of research. Driven by the need for new therapies to treat a range of muscle-associated diseases, these strategies aim to provide improved drug exposure at the site of action in skeletal muscle with reduced concentration in other tissues where unwanted side effects could occur. By interacting with muscle-specific cell surface recognition elements, both tissue localization and selective uptake into skeletal muscle cells can be achieved. The design of molecules that are substrates for muscle uptake transporters can provide concentration in m uscle tissue. For example, drug conjugates with carnitine can provide improved muscle uptake via OCTN2 transport. Binding to muscle surface recognition elements followed by endocytosis can allow even large molecules such as antibodies to enter muscle cells. Monoclonal antibody 3E10 demonstrated selective uptake into skeletal muscle in vivo. Hybrid adeno-associated viral vectors have recently shown promise for high skeletal muscle selectivity in gene transfer applications. Delivery technology methods, including electroporation of DNA plasmids, have also been investigated for selective muscle uptake. This review discusses challenges and opportunities for skeletal muscle targeting, highlighting specific examples and areas in need of additional research.

Report this publication

Statistics

Seen <100 times