Drug Discovery Opinion

Wnt signalling plays an important role in the development and maintenance of many organs and tissues, and appears to be especially important in regulating bone mass. Enhanced Wnt signalling has the potential to speed up healing and mice genetically modified to have prolonged Wnt signalling heal more quickly than control mice. So far it hasn’t been possible to directly test the effect of administering Wnt ligands because of difficulties in purifying and formulating the proteins, but researchers at Stanford University School of Medicine have now solved the problem by packaging the proteins in liposomal vesicles.

When Wnt3a-loaded liposomes were administered to mice with bone injury, within 3 days the animals had 3.5 times more new bone growth than animals that received no treatment or animals that received Wnt protein without the carrier liposomes. After 4 weeks, the bone had completely healed in the animals treated with Wnt-carrying liposomes whereas untreated animals took another 2 weeks. Wnt was shown to act by increasing the proliferation of bone progenitor cells – Wnt-responsive cells are found on the inner surface of the bone and participate in normal bone maintenance and in bone growth in response to injury. A liposomal formulation would also be suitable for use in people and could, after much further evaluation, be used to speed bone healing. Members of the bone morphogenetic protein family are currently used in spinal fusions and to treat some fractures but can cause bone to grow in the wrong place.

In some animals, such as flatworms and zebrafish, the Wnt pathway allows tissue regeneration without scarring and the authors hope that their study might also provide the basis for new treatments for stroke and heart attack where scar tissue formed as part of the normal healing process impairs later function.

The study is published in Science Translational Medicine.

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