Faecal Incontinence: About The Condition

FI is a substantial public health problem. It has a major impact on quality of life causing stigmatization and social isolation. AMELIE is primarily concerned with the effect of injury to the anal sphincter by either childbirth, surgery or trauma. Women who have given birth form the majority of patients who present with FI. A significant proportion of women (reported incidence of 5.5%) suffer a direct injury during childbirth due to tearing of the perineum. 

The current management of patients with FI is unsatisfactory. Patients with anal sphincter injury are commonly treated by surgery, however many with severe symptoms are either unsuitable for, or do not wish to undergo, current available surgical options. For these patients, an option that does not have the risks of sphincter repair or the long-term maintenance of an active metal implant is attractive. This is the place of regenerative medicine.

Faecal Incontinence and Regenerative Medicine

Regenerative medicine aims to restore functional tissue that is impaired due to aging, disease or injury. It offers new opportunities to restore incontinence caused by anal sphincter injury. To date, cell therapy using ASMDC to regenerate the damaged external anal sphincter muscle has been the most extensively investigated approach.

Europe has established a predominant position in the clinical translation of cell therapy in FI patients. Among the five published cell therapy clinical studies performed to date, three have used ASMDC and originated from European units. These studies have comprised of delivering cells in a suspension. Only 58% of the patients treated with ASMDC showed a response at 12 months in the Phase II randomised placebo-controlled study. Open pilot studies have reported a similar level of subjective improvement. The overall outcomes of these studies have, so far, reported only limited benefit to the patients treated suggesting an inconsistent mechanism of action with the current approach to cell-based treatment for FI.

Why Are Conventional Methods Not Working?

Anchorage-dependent cells must be cultured while attached to a substrate. Conventional manufacture of anchorage-dependent cells for regenerative medicine cell-based therapies involves the isolation of cells from a host tissue and their subsequent growth in a favourable in vitro environment. All of the published cell therapy clinical investigations for FI to date have used conventional bioprocessing techniques. However, the process of detaching the ASMDC from their culture substrate in readiness for clinical delivery risks viability and potency, initiating anoikis (cell death).

Reduced cell viability due to anoikis is a major challenge to regenerative medicine. None of the approaches are currently suitable for ASMDC treatment of FI where engraftment into host muscle is required. The impact of anoikis on regenerative medicine products consisting of anchorage-dependent cells hinders clinical efficacy due to the inconsistency caused by the low survival rate of transplanted cells.

This is the challenge AMELIE is facing. Find out about latest developments here.