Impact of oral disulfiram on ALDH-mediated fibrosis in ocular pemphigoid (MMP-Oral-DSF)

• Research type

  Research Study

• Full title

  Impact of Oral Disulfiram on Aldehyde Dehydrogenase (ALDH) Mediated Ocular Fibrosis in Mucous Membrane Pemphigoid (OcMMP). An experimental medicine study evaluating oral disulfiram repurposed to probe the ALDH mediated profibrotic mechanism in ocular disease (MMP-Oral-DSF)

• IRAS ID

  1009671

• Contact name

  Saaeha Rauz

• Contact email

  s.rauz@bham.ac.uk

• Sponsor organisation

  University of Birmingham

• ISRCTN Number

  ISRCTN99747720

• Research summary

  Conjunctival scarring results from many diseases. These include trachoma, an infection that is known to be the largest cause of preventable blindness worldwide. It causes irreversible sight-loss in both eyes in 1.9 million people worldwide. In the UK, the most common cause is a rare autoimmune driven disorder called Ocular Mucous Membrane Pemphigoid (OcMMP) that occurs in 0.8 people per one million of the population each year. OcMMP creates chronic inflammation and scarring of the conjunctiva which lines the inside of the eyelids and covers the white of the eye. Scarring of the inside lining of the eyelid can cause the lashes to turn inwards and scratch the cornea (trichiasis). This and inflammation, lead to debilitating symptoms of constant irritation, pain, and dryness. Treatments involve immunosuppression but this has little effect on scarring. For half of patients, scar formation continues; 20% become irreversibly blind. Aldehyde Dehydrogenase (ALDH) is thought to drive this scarring process.
  Disulfiram is a drug given by mouth as an alcohol deterrent treatment which permanently blocks ALDH action. We would like to understand whether disulfiram has the same impact if given to patients with OcMMP. As there is no licensed disulfiram eyedrop formulation, we would like to give tablets by mouth at the UK licensed safe dose, to patients with OcMMP for two weeks and examine how it effects the scarring signals in the conjunctiva. We will do this by taking swabs, tear, blood and faecal samples from patients before starting treatment, one week into treatment, at the end of treatment and during the two-week period after coming off treatment.

• REC name

  London - Chelsea Research Ethics Committee

• REC reference

  24/LO/0588

• Date of REC Opinion

  30 Aug 2024

• REC opinion

  Further Information Favourable Opinion