The Biology of GDF Proteins

Growth and Differentiation Factors (GDFs) are potent, naturally occurring molecules that play a key role in the growth and repair of various tissues. These protein families regulate the cellular proliferation, differentiation, and survival of several major tissue types. Acceleron is developing therapies based on GDF biology to target diseases that affect bone, muscle, vasculature, and fat.

Powerful and Precise Control Over Tissue Growth and Repair

Normal tissue growth and repair depends on an intricate network of checks and balance which governs the timing and amount of tissue production. At the center of this network is the GDF family of proteins, whose rich biology enables them to exert fine control over these processes:

Over 30 different protein ligands have been characterized, and an even greater number of subtypes
GDF ligands have diverse functions, including both positive and negative regulators which promote and inhibit growth of specific types of cells or tissue.
A diverse array of receptors specific to GDF proteins, elicits a variety of cellular responses upon binding
Ligands are themselves subject to control by their own antagonists, activators, feedback mechanisms, and other protein families
Influence and control over a wide variety of tissue types: bone, muscle, vasculature, fat

The result is a highly sophisticated and powerful system for regulating tissue growth throughout the body.

Immense Therapeutic Promise of the GDF Family

The GDF proteins are attractive targets for drug development and have enormous clinical potential. Successfully tapping into the GDF tissue control mechanisms would create an entirely new class of therapies that treat disease by modulating tissue growth. This paradigm shift from current therapeutic approaches to therapies that affect entire tissues or organ systems have already proven to be a highly effective strategy in cancer.

For example, angiogenesis inhibitors, which control the growth and proliferation of the vasculature, are now a critical part of treatment regimens for solid tumors and have increased response rates and extended survival for cancer patients. Instead of directly targeting tumor cells, these products work by inhibiting vessel growth, thereby cutting off the supporting blood supply to tumors. Successfully harnessing the power of GDF-mediated mechanisms, however, could open treatment possibilities to the broad spectrum of diseases that involve bone, muscle, and fat, as well as vascular tissue.

While several highly effective, locally-acting agents have been developed which demonstrate the potential of GDF biology, technical constraints have prevented the successful development of therapies that can treat the much larger group of systemic diseases. By taking an entirely novel approach, however, Acceleron has developed technology that has unlocked the immense therapeutic potential of GDF biology.

How Acceleron is Harnessing the Power of GDF Biology