Glial cell line-Derived Neurotropic F... - Parkinson's Movement

Parkinson's Movement
17,408 members17,275 posts

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.

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.

2 Replies

Puerarin Protects Dopaminergic Neurons against 6-Hydroxydopamine Neurotoxicity via Inhibiting Apoptosis and Upregulating Glial Cell Line-Derived Neurotrophic Factor in a Rat Model of Parkinson's Disease (Puerarin is Kudzu.)

Reversal of dopamine neurons and locomotor ability degeneration in aged rats with smilagenin.

"Furthermore, smilagenin enhances glial cell-derived neurotrophic factor (GDNF) release both in the striatum and midbrain. These results indicate a possible role of smilagenin in the treatment of age-related extrapyramidal disorders."

Plants that have smilagenin as an active component:

A Chinese herbal decoction, reformulated from Kai-Xin-San, relieves the depression-like symptoms in stressed rats and induces neurogenesis in cultured neurons

"The protein levels of NGF, BDNF and GDNF in cortex were markedly decreased in CMS-induced depressive rat cortex; however, this reduction was alleviated after KXS2012 treatment (Fig. 3A)."

Protective effect of the green tea component, L-theanine on environmental toxins-induced neuronal cell death.

"Furthermore, pretreatment with L-theanine significantly attenuated the down-regulation of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) production in SH-SY5Y cells."

Vitamin D3 promotes dopamine neuron survival through up-regulation of GDNF

The Role of Vitamin D3 in the Development and Neuroprotection of Midbrain Dopamine Neurons

You may also like...