Neurotrophic factors are small proteins that support the growth and survival of neurons. Neurotrophic factors function by binding specifically to the cell surface receptors that signal the neuron to survive. In addition to promoting neuron survival and suppressing new lesion formation, neurotrophic factors are capable of regenerating and regrowing damaged neurons.
The neurotrophic employed in this process - Glial cell-Derived Neurotrophic Factor (GDNF) - is well known for its effectiveness in halting and potential reversal Parkinson's Disease progression. GDNF’s most prominent feature is its ability to increase the survivability of dopaminergic neurons and has been repeatedly proven to be highly effective in ameliorating Parkinson's-like symptoms in both small and large animal models. GDNF protects neuron degeneration irrespective of the underlying pathology. This means that regardless of the reason for neuron degeneration, GDNF will halt Parkinson’s Disease progression with some evidence of neuro-restoration.
Several clinical trials in humans failed to indicate clinical benefit to patients. However, an ever-growing body of evidence from follow-up biopsies and analyses indicate that the primary reason for failure to achieve efficacy lies with inadequate delivery methods used to transport GDNF to the specific areas of the brain where it is needed most.
Macrophage-mediated drug delivery of GDNF for Parkinson’s Disease is a novel approach to leverage the natural attraction of macrophages to inflammation caused by neuron degeneration to effectively deliver neurotrophic factors to the areas of the brain needed most. The strength of macrophage attraction is relative to the amount of inflammation, resulting in macrophage drug delivery only when needed. Engineering of CD34+ cells is accomplished using a macrophage-specific promoter, limiting drug production to macrophages as opposed to all CD34+ cell lineages.
Proof of Concept pre-clinical studies with this technology were completed in two distinct and widely used mouse models of Parkinson's Disease 1) the acute toxin MPTP mouse model and 2) the progressive genetic MitoPark mouse model. Results from these studies were peer reviewed and published in multiple scientific journals.