Congenital Erythropoietic Porphyria (CEP): Our lead project targets the autosomal recessive deficiency in the uroporphyrinogen III synthase (UROIIIS) enzyme in the haeme group biosynthetic pathway. To date, 28 mis-sense mutations producing CEP have been reported in the literature, a vast majority of which result in an increase in the kinetic aggregation rate of UROIIIS. Deficiency in UROIIIS leads to a build-up in the body of porphyrins in high concentration (e.g., in bone, the bone marrow, red blood cells, plasma, urine, faeces, teeth and skin) which are damaging to tissues resulting in a range of significant symptoms for patients. This project is currently at the lead identification/optimisation phase.

Prion Disease: Prion disease (e.g., Creutzfeldt-Jakob disease) results from the progressive accumulation of an abnormal form of the naturally occurring cellular prion protein leading to subsequent adverse effects on brain function and ultimately death. This project is at the hit identification phase of discovery.

Tyrosianemia: Mutations in the fumarylacetoacetate hydrolase FAH gene cause human tyrosianemia, an inborn error of metabolism characterized by accumulation of multiple abnormal compounds in both the blood and urine: tyrosine, methionine, tyrosine metabolites and succinylacetone. This project is at the hit validation of therapeutic chaperones.

Other diseases: We are currently assessing a range of other diseases to initiate further projects which will benefit from a pharmacological chaperone therapeutic.