About PB01

PB01 is recombinant human follistatin-288, the most potent form of follistatin. It is a novel biological molecule with strong anti-inflammatory and anti-fibrotic actions. PB01 binds to and neutralises the activity of the TGFß superfamily of growth and differentiation cytokines, most notably the activin family, thereby inhibiting the production of proinflammatory cytokines.

About Follistatin

The follistatin gene is found on the long arm of human chromosome 5 (5q11.2). It is a highly conserved molecule with 98% identity between human follistatin and mouse follistatin, indicating its fundamental importance in biology.

The follistatin gene consists of six exons (from which mature proteins are built), resulting in a protein that has the following elements as shown diagrammatically below:

About Follistatin

Each follistatin molecule has three similar domains, known as follistatin domains (FSD), varying individually at the amino acid level but having the same structural features. The two major forms of follistatins are FS315 and FS288.

Follistatin’s primary function results from its ability to bind and block the effects of activins. Activins are key members of the transforming growth factor beta (TGFß) superfamily of growth and differentiation cytokines.

When a molecule of follistatin meets a molecule of activin, this results in an almost irreversible binding event that prevents activin from binding to its specific receptors and causing gene activation. The activin molecule is a dimer comprising two identical or similar ß subunits. Two molecules of follistatin are required to fully neutralize an activin molecule, as shown in the schematic below:

follistatin

In addition to activin, follistatin also binds with lower affinity to other members of the TGFß superfamily, including bone morphogenetic proteins (BMP’s) 2, 4, 5, 6, 7, 11 and 15 and myostatin growth development factors GDF8 and GDF9. Follistatin does not bind to TGFß1 or TGFß2, but can bind to TGFß3.

Follistatin is a glycoprotein. This glycoslyated nature of follistatin affords increased stability of follistatin in vivo. In addition, follistatin contains a heparin binding sequence (HBS) that enables follistatin to bind to proteoglycans on cell surfaces and in the extracellular matrix.