Oct. 7, 2008

Utrophin Gene Transfer Aids Mice With Severe MD

A research team coordinated by MDA grantee Jeffrey Chamberlain at the University of Washington-Seattle found intravascular gene transfer with a miniaturized utrophin gene had roughly the same benefits as intravascular gene transfer with a miniaturized dystrophin gene in mice missing both utrophin and dystrophin and showing a severe disease resembling Duchenne muscular dystrophy (DMD).

Like dystrophin, the protein missing in boys with DMD, utrophin is a muscle protein. However, boys with DMD make this protein, and its similarity to dystrophin has prompted researchers to experiment with its ability to compensate for dystrophin's loss. The advantage of using utrophin instead of dystrophin for gene transfer in DMD is that patients' immune systems are used to "seeing" it and are unlikely to reject it as foreign protein.

The muscles of mice that received intravenous utrophin genes in a viral delivery vehicle showed improvements in structure and function.

"In moving toward clinical applications of ... gene transfer, the potential immune responses of the host ... will need to be carefully considered," the authors note in their paper, published in the September issue of Molecular Therapy. "Given that utrophin is normally expressed in nearly all tissues, including muscle, the results reported here suggest that gene therapy protocols for DMD could potentially benefit from the use of utrophin-based transgenes."