Glial cell line-Derived Neurotropic Factor (GDNF) a disease-modifying therapy

Over the past two decades, biotech companies and clinicians have tried to develop a cure for Parkinson’s disease based on Glial cell line-Derived Neurotrophic Factor (GDNF), a naturally occurring factor promoting the growth of dopamine neurons. Some clinical results were stunning, with patients experiencing a spectacular improvement in their symptoms and a return to 'normal' life. However, delivery of GDNF has been a major challenge. As it cannot be absorbed orally, a variety of delivery methods have been tested including direct pumping into the brain, intranasal delivery and gene therapy. Newly formed Mavalon Therapeutics is developing the first orally available small molecule able to induce GDNF production within the brain of Parkinson’s patients, a treatment that will bring benefits to a larger population than the current intra-brain delivery of GDNF.

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The Glial cell line-Derived Neurotropic Factor (GDNF) is a growth factor promoting neuronal survival and growth that focused the attention of the pharma industry as the basis of a disease-modifying therapy. The main challenge remains the delivery of this growth factor. Several ongoing trials use different routes and modes of direct administration of GDNF (either invasive based on surgery or via viral particles) with limited results due to delivery heterogeneity.

mGluR3 receptor has been shown - by Ferdinando Nicoletti’s group in Italy - to promote GDNF production when activated by glutamate release. The glutamate is released by degenerating neurons in the brain of Parkinson’s patients. The mGluR3 PAM drug candidate that Mavalon is developing will further induce a physiological GDNF production at the site of neuron degeneration.

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