Title: Small molecule AhR antagonists for the treatment of Duchenne Muscular Dystrophy
Funder: Action Medical Research

Abstract: Background_x000D_ Duchenne muscular dystrophy (DMD) is a genetic disease which causes muscle wasting and weakness. Children with DMD have a faulty gene which means they cannot produce dystrophin, a protein which protects muscles. Affecting around 100 boys born in the UK each year, DMD is usually diagnosed between the ages of three and five years when affected children start to have difficulty walking or running. Progressive muscle wasting and weakness occurs and although life expectancy is increasing, sadly, most people with DMD do not live beyond their forties. _x000D_ Utrophin is a protein related to dystrophin and has the potential to act as a substitute for dystrophin potentially benefitting children with DMD. These researchers have already investigated one possible drug treatment designed to increase the amount of utrophin in muscle cells. They now want to extend their work to study other compounds which could lead to the development of a utrophin replacement therapy._x000D_ _x000D_ The research project_x000D_ Although the first drug treatment investigated showed some initial promise, it was not effective over a longer period. The team therefore decided to look in detail at its mode of action as this could help identify other similar but more effective drugs. They have now found a number of new compounds which act in a similar way to increase utrophin production. This project will focus on further developing and testing these new compounds in the laboratory to identify a potential candidate for clinical drug development. _x000D_ There is currently no curative treatment for DMD and although significant progress is being made with gene therapy, this is not suitable for all children. A big advantage of utrophin replacement therapy as a treatment approach is that it is potentially suitable for all patients with DMD regardless of their specific gene mutation. This project could ultimately result in a new drug to help all children with DMD by slowing disease progression. _x000D_ _x000D_ Action Medical Research and LifeArc are jointly funding this research._x000D_

Lay abstract: Background_x000D_ Duchenne muscular dystrophy (DMD) is a genetic disease which causes muscle wasting and weakness. Children with DMD have a faulty gene which means they cannot produce dystrophin, a protein which protects muscles. Affecting around 100 boys born in the UK each year, DMD is usually diagnosed between the ages of three and five years when affected children start to have difficulty walking or running. Progressive muscle wasting and weakness occurs and although life expectancy is increasing, sadly, most people with DMD do not live beyond their forties. _x000D_ Utrophin is a protein related to dystrophin and has the potential to act as a substitute for dystrophin potentially benefitting children with DMD. These researchers have already investigated one possible drug treatment designed to increase the amount of utrophin in muscle cells. They now want to extend their work to study other compounds which could lead to the development of a utrophin replacement therapy._x000D_ _x000D_ The research project_x000D_ Although the first drug treatment investigated showed some initial promise, it was not effective over a longer period. The team therefore decided to look in detail at its mode of action as this could help identify other similar but more effective drugs. They have now found a number of new compounds which act in a similar way to increase utrophin production. This project will focus on further developing and testing these new compounds in the laboratory to identify a potential candidate for clinical drug development. _x000D_ There is currently no curative treatment for DMD and although significant progress is being made with gene therapy, this is not suitable for all children. A big advantage of utrophin replacement therapy as a treatment approach is that it is potentially suitable for all patients with DMD regardless of their specific gene mutation. This project could ultimately result in a new drug to help all children with DMD by slowing disease progression. _x000D_ _x000D_ Action Medical Research and LifeArc are jointly funding this research._x000D_

Research activity codes: 5.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL