Cultured Autologous Oral Mucosa Epithelial Sheet for the Treatment of Bilateral Limbal Stem Cell Deficiency

Condition(s) studied

Investigational drug(s) / intervention(s)

FEMJA transplatation: The cultivated oral mucosal epithelium will be directly grafted onto the corneal stroma. The sheet is grafted without suture onto the exposed stromal bed after removal of the conjunctiva and fibrosis from the cornea. The grafted corneal surface is then covered with a soft permanent contact lens for protection during healing (between 3 to 15 days, according to tolerance) If the stroma appears opaque because of deep stromal scars a corneal allograft will be performed 12 months after FEMJA transplantation.

Study summary

Some severe ocular burns or other rare ocular pathologies can be associated with a total loss of corneal epithelial stem cells (i.e. Limbal Stem Cell Deficiency - LSCD), which leads to cornea invasion by the conjunctiva and a subsequent opacification. When LSCD is total and bilateral, both eyes are affected leading to full blindness and a poor quality of life, with a paradoxical photophobia that may be painful. Fewer than 100 patients bear this rare condition in France.

When patients suffer from total and bilateral LSCD, no treatment has been proven to provide clinical benefits: contralateral limbus is unavailable for autologous limbus graft or autologous limbal stem cells culture; allogeneic limbus graft requires immunosuppressive treatment leading to too important serious adverse effects compared to the expected benefit, and does not last long (\< 2 years); and allogenic cornea transplantation is impossible since always rejected due to neovascularization.

A new way to treat these patients is to cultivate autologous corneal-like epithelium, and to graft it in order to restore transparency and to allow, if needed, a complementary corneal graft. Such an epithelium can be produced from autologous jugal mucosa cells. Epithelial jugal mucosa sheets transplantation has been assessed in a phase I/II clinical trial on 26 patients which showed that it is well-tolerated and effective but the culture technology used in this clinical trial is no longer available. A new enzymatic detachment process has been developed by the Hospices Civils de Lyon. Proof of concept was obtained from both in vitro and ex vivo studies: detachment with Collagenase at 0.5 mg/mL doesn't damage basement membrane proteins, so collagenase 0.5mg/mL-detached FEMJA were found to adhere, continue to ensure renewal of the differentiated epithelium 15 days after grafting onto an ex vivo porcine de-epitheliazed stroma model.

Considering these results, we aim to perform a clinical trial in order to evaluate tolerance and efficacy of the autologous jugal mucosa cell sheet (Feuillets Epithéliaux de Muqueuse Jugale Autologue - FEMJA) cultured with this innovative process.

Eligibility

Primary outcome measure(s)

• Number of patients with any improvement in visual acuity — 24 months after FEMJA transplantation
  Visual acuity measured at baseline (preoperative status) and 24 months after a jugal mucosa epithelial cell sheet transplantation (FEMJA transplantation), according to the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. ETDRS LogMAR tests allow measurement of very low visual acuity.

Trial sites (1)

More Hospices Civils de Lyon trials in France