In heart failure, companies with expertise in gene or cell biology, or percutaneous delivery devices, see the first application where regenerative medicine could finally realize its promise. The enormous patient population, the high mortality of the disease, and the economics of treating it today provide a multi-billion dollar opportunity for which it's worth braving the complexity of cell therapy for tissue repair. Indeed, first-generation autologous heart cell therapies involve many different types of expertise resident in companies with different mindsets. Unknowns dog every component of the therapies on the level of basic biology. Still to be worked out: the right cell types; the optimal delivery route and device; when and at what dose cells should be administered, and in combination with which genes or drugs. Nevertheless, the great need in heart failure keeps companies dedicated to cardiac regeneration therapies. And as the cell therapy developers reveal new discoveries about the innate regenerative powers of the heart, drug developers are starting to move in, promising a much simpler approach than the combination products presently in the works.

As regulators increase their scrutiny of viral vectors for gene therapy and set the bars for safety ever higher, some industry observers have begun questioning whether gene therapy will ever become a commercial reality. The difficulties in the field may turn out to be a life-saver for MaxCyte Inc. Its managers think their flow electroporation technology could be a platform for transforming patients' cells and getting them to produce a desired protein--without viruses, and the risks they bring.

Innovative device companies have always had to contend with the Sword of Damocles of unexpected technological obsolescence, but for would-be developers of interventional devices for the prevention of restenosis, the sword is dangling perilously close. In the RAVEL trial, a 238-patient clinical trial on a drug eluting stent, treated patients experienced 0% restenosis compared to 26% in the control group. Now, device developers with alternatives to stents reposition themselves to sustain businesses in the face of potentially shrinking target markets. Many argue that they will serve certain applications better than stents; others hope to work with drug-coated stents to enhance performance, many believe that economics will leave room for alternative approaches, and still others are getting out of the coronary business entirely.

Montreal-based Angiogene Inc. is developing Radiolabelled DNA for proliferative disorders, initially restenosis.