Hedgehog for Parkinson's disease
therapeutic benefit in patients suffering from Parkinson's disease,
says study.
Stimulation of the Hedgehog signalling pathway could have a therapeutic benefit in patients suffering from Parkinson's disease, according to a report in the online version of The FASEB Journal.
The preclinical study shows that the Sonic Hedgehog protein acts as a neuromodulator, reducing the activity of nerve cells in the subthalamic nucleus of the brain. This region is known to be abnormally stimulated in Parkinson's disease, and increased levels of nerve activity there contribute to the movement disorders characteristic of the condition.
The hope is that the development of drugs that can stimulate the Hedgehog pathway could provide an alternative treatment to surgery in Parkinson's patients.
The research is based on preclinical research performed at several laboratories, including the Universite Victor Segalen in France, the University of Manchester in the UK, and the Toronto Western Research Institute in Canada. Consistent with the finding that Hedgehog signalling can modulate nerve cell activity, the authors also observed that Hedgehog signalling is abnormally reduced in a model of Parkinson's disease. This finding suggests that reduced levels of Hedgehog signaling may play a role in the pathology of Parkinson's disease.
A US biotechnology company, Curis, is developing drug candidates that activate the Hedgehog signalling pathway for the treatment of Parkinson's disease and other neurological disorders. These small-molecule drug candidates can be given orally and readily reach the brain to stimulate the Hedgehog signalling pathway in preclinical animal models.
Dr Lee Rubin, Curis' chief scientific officer, said: "We have already demonstrated that administration of Hedgehog protein or small molecule Hedgehog agonist drugs can promote recovery in animal models of Parkinson's disease. This report increases our understanding of the potential mechanisms of action by which our drug candidates exert these positive effects."
Last month, two reports in Nature provided evidence that Hedgehog signalling may also be involved in the development of certain cancers, including pancreatic cancer. Curis entered into an agreement with Genentech in June to develop Hedgehog-based drugs as cancer therapeutics.
