My aching heart

Locked away behind the rib-cage our hearts beat 100,000 times each day, delivering the essential components of life to every cell in the body. Equally exalted and lamented by lovers, the heart is rightly identified as a vulnerable organ.

For many years, the excesses associated with the Western lifestyle have been known to play a role in the epidemic of cardiovascular disease (CVD) affecting the populations. Thanks to an increasing understanding of disease pathology, lifestyle intervention and ongoing therapeutic development disease incidence is reducing. For example, fewer people in the UK today will be expected to die of a failing heart before the age of 75 than at any time in the last 50 years. However, the epidemic continues.

Strategies for treating CVD have focused on physical and therapeutic mechanisms that can improve the supply of blood to the heart tissues. Under stress, the heart has the inherent ability to achieve this through a process of new blood vessel growth, called angiogenesis. However, the process is slow and easily outpaced by disease. To stimulate collateral vessel growth and boost the heart's natural ability to heal itself, Cardium Therapeutics have developed a novel therapy consisting of an adenovirus containing the recombinant FGF-4 gene, called Generx. This new product is being specifically developed for patients with a CVD condition termed cardiac microvascular insufficiency (CMI). Researchers at Cardium found that a growth factor gene carried by an adenovector can trigger a stunning revascularisation of a heart with coronary artery blockages. Patients with CMI have an insufficient angiogenic response and may benefit from this new therapy where cardiac perfusion is biologically enhanced via the formation of collateral blood vessels. Over 450 patients with coronary artery disease have received the drug in clinical testing. As yet, overall therapeutic efficacy has not been overwhelming. However, it is apparent from preclinical and clinical data that success is better in patients with more severe disease and acute cardiac insult.

The findings of the ongoing ASPIRE study, which uses short-term standardised angioplasty balloon occlusion to induce transient ischemia during delivery of the gene therapy, are eagerly awaited. Recently published findings demonstrate that this innovative technique dramatically enhances gene delivery and transfection. Has transfection technology finally matured? Concerns that are frequently voiced include: will the vector be able to find and enter its designated target?; Will the transgene insert randomly into the genome or be diluted on host cell replication; Is the vector immunogenic?; Can sufficient quality vector be produced for clinical use? The ASPIRE study attempts to overcome these potential previously reported sources of high inter-individual variability.

There is no doubt of the need for new treatment options for CVD. Long term studies have demonstrated that well-developed microvascular collateral networks in the heart save lives. However, in the face of increasing development costs and regulatory requirements, the focus of industry pipelines has shifted toward orphan indications and oncology targets that currently offer shorter development pathways and more lucrative opportunities for reimbursement. Nevertheless, the small team of passionate scientists and clinicians at Cardium may be on the threshold of a new treatment paradigm for cardiovascular disease. It is estimated that more than 17 million people worldwide died from CVDs in 2008; 3 million of these were people under 60 years of age. (Read Global Atlas on cardiovascular disease prevention and control 10mb pdf).

Surely this opportunity will not be overlooked by the pharmaceutical industry.