Small Molecules: Offering hope for people with FSHD

A treatment or cure for FSHD could come from many avenues, gene therapy, stem cell therapy, the development of physical therapies. One potential that many researchers across the globe are exploring is small molecules. These are molecules that are small in size and are biologically active, that is, they influence processes that happen in the body. Most medicines that are available are small molecules.

The creation of large molecule libraries, and the development of high throughput screening methods means that researchers can screen thousands of molecules looking for the ones that produce the effect they want. Small molecule screens offer a powerful tool for researchers to discover not only new medicines, but also uncover new processes that might explain the biology of conditions. Which, completes the circle, by providing new targets for drug-discovery. The screening of small molecule libraries is used routinely in the pharmaceutical industry to find new medicines to treat a diverse range of conditions.

Small molecule screens usually come in two forms. The first is taking a library of biologically active molecules, adding them to cells and seeing if they produce changes in particular proteins or cellular processes. The second is to take your library, add it to a cell system and see whether any cause desired changes in the way the cells behave.⁽¹⁾

FSHD Global have funded research that uses both these types of approaches. These research projects have the potential to discover new medicines for the treatment of FSHD. The approaches are diverse, one project lead by Australian researchers Stephen Palmer and Leslie Caron is screening a set of molecules to see how they affect the development of muscle cells. Professor Michael Kyba from the USA has screened over 35,000 compounds to see if any alter the activity of DUX4 – one of the main genes thought to be responsible for the development of FSHD. Davide Gabellini from Italy has discovered an entirely new mechanism for controlling the genetic area where the mutations involved in FSHD are located. The team are screening molecules that will keep this genetic switch turned off, the effect of this could be to switch off the mutations that cause FSHD.

FSHD Global will continue to work with researchers from around the world and, through the continued support from our community, we will be able to offer funding to help them develop actual treatments for FSHD from promising small molecules.

If you have any questions about this article, or the medical research that FSHD Global is currently supporting please contact the Foundation admin@fshdglobal.org
1. Eggert US. The why and how of phenotypic small-molecule screens. Nature chemical biology. 2013;9(4):206-9.