Assessing gene and cell therapies applied in striated skeletal and cardiac muscle: Is there a role for nuclear magnetic resonance? A. Leroy-Willig a, * , Y. Fromes b , M. Paturneau-Jouas b , P. Carlier a a NMR Laboratory (AFM – CEA), Institute of Myology, Pitie ´-Salpe ˆtrie `re University Hospital, 47 Boulevard de l’Ho ˆpital, Cedex 13, 75651 Paris, France b INSERM U523, Institute of Myology, Pitie ´-Salpe ˆtrie `re University Hospital, Paris, France Received 9 September 2002; received in revised form 6 January 2003; accepted 16 January 2003 Abstract Gene and cell therapies convey high hopes for treatment of skeletal and heart muscle diseases. In the experimental protocols under development as well as in the first clinical trials, longitudinal control by an atraumatic procedure is needed. Nuclear magnetic resonance (NMR), via its two modalities, imaging or spectroscopy, should play a major role both for in vivo animal and human studies, because of the great number of parameters that can be measured, sequentially or simultaneously, and because of its aptitude to monitor several steps of protocols, in particular to detect physiological modifications induced by therapies. We review here the many possible applications of nuclear magnetic resonance in gene/cell therapies where muscle is the target organ, with emphasis on the application of nuclear magnetic resonance to functional studies. q 2003 Elsevier Science B.V. All rights reserved. Keywords: Gene; Gene therapy; Cell transplantation; Nuclear magnetic resonance; Skeletal muscle; Heart 1. Introduction Since the pioneer clinical trial of Rosenberg et al. [1], gene therapy (GTh) may be considered as the next frontier in the medical field, although for many potential appli- cations, there is still a long way to go and many steps from small animal studies to human applications. Aims of GTh are to correct a genetic defect (e.g. inducing the production of a missing enzyme or protein), to restore a function (e.g. production of a therapeutic factor) or to introduce a new function (e.g. apoptosis), via the incorporation of the therapeutic DNA and its expression inside cells. Cell therapy (CTh) also conveys high hopes of repair to damaged tissue, in central nervous system (CNS), and in striated skeletal and heart muscle. For instance, myoblast transplantation, recently attempted in human myocardium [2], may contribute to cardiac function improvement in patients with severe ischaemic cardiac deficiency. The combination of these two modalities, GTh and CTh recently led to the first success of a GTh applied to a severe human disease [3], where gene engineering was applied ex vivo to the cells, and later reinjected into bone marrow. Major impacts of these technologies are expected in the therapy of malignant tumours and of neurodegenerative and cardiovascular diseases. Inherited enzymatic deficiencies also are an important target. In the domain of neuromuscular disorders, many diseases are directly related to a monogenic defect, making GTh a particularly attractive approach. However, major difficulties arise from the large volume of diseased muscle tissue. In most small animal studies, evaluation of gene expres- sion is performed through tissue examination after animal sacrifice, and repeated studies on different animals are necessary for longitudinal follow-up. As an alternative, repeated examinations of the same animal decrease scattering associated with interindividual variance and diminish experimental work and cost. On the human side, gene expression in muscle subjected to GTh will most likely be evaluated by studies of muscle biopsies. However, biopsies probe a small, often blindly chosen, part of the muscle and cannot be repeatedly performed. Thus atrau- matic tools are greatly needed either to choose optimal biopsy site, or to locally control the efficiency of gene or cell 0960-8966/03/$ - see front matter q 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S0960-8966(03)00035-X Neuromuscular Disorders 13 (2003) 397–407 www.elsevier.com/locate/nmd * Corresponding author. Tel.: þ 33-1-42165892; fax: þ 33-1-42165887. E-mail address: a.leroywillig@myologie.chups.jussieu.fr (A. Leroy-Willig).