Palisades Therapeutics announces possible breakthrough treatment for Parkinson's disease

Neuroprotective Efficacy of the Glucocorticoid Receptor Modulator PT150 in the Rotenone Mouse Model of Parkinson's Disease
CLIFFSIDE PARK, N.J. - April 30, 2024 - PRLog -- Pop Test Oncology/Palisades Therapeutics' collaborators at Colorado State University led by Ronald Tjalkens, PhD and Richard Slayden, PhD, post pre-print of latest study results on BioRxIV.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder worldwide. Current treatments for PD largely center around dopamine replacement therapies and fail to prevent the progression of pathology, underscoring the need for neuroprotective interventions.

Approaches that target neuroinflammation, which occurs prior to dopaminergic neuron (DAn) loss in the substantia nigra (SN), represent a promising therapeutic strategy. The glucocorticoid receptor (GR) has been implicated in the neuropathology of PD and modulates numerous neuroinflammatory signaling pathways in the brain.

Results indicate that treatment with the clinical stage GR-antagonist PT150 reduced both loss of DAn and microgliosis in the nigrostriatal pathway in one of the most important animal models for the human disease. Although morphologic features of astrogliosis were not attenuated, PT150 treatment promoted potentially neuroprotective activity in these cells, including increased phagocytosis of hyperphosphorylated α-syn.

Ultimately, PT150 treatment reduced the loss of DAn cell bodies in the SN, but not the striatum, and prohibited intra-neuronal accumulation of α-syn. Together, these data indicate that PT150 effectively reduced SN pathology in the rotenone mouse model of PD.

The data suggest that pharmacologic antagonism of GR is neuroprotective in the rotenone model of PD by altering pro-inflammatory glial responses.

Altogether, these findings effectively illuminate neuroprotective mechanisms of targeting the GR to impede PD neuropathology.

According to lead scientist Ronald Tjalkens, PhD, "In this study, we used a common model of mitochondrial dysfunction in Parkinson's disease (PD) in which most neuronal loss occurs after the initial stress-induced cellular damage. The inflammatory response to this neuronal injury is responsible for most of the loss of dopamine neurons in this model. In animals given PT150 orally after the initial lesioning period, we saw a marked reduction in measures of cellular inflammation that correlated with preservation of the number of dopamine neurons. This is a very promising finding and suggests that this orally bioavailable drug could be neuroprotective as a disease-modifying therapeutic for PD."

Pop Test Oncology/Palisades Therapeutics' lead scientist Neil Theise, MD and his team are excited to see that PT150 showed neuroprotective properties in a pre-clinical model of Parkinson's disease. "The findings of this study suggest that this drug could be a promising therapeutic for neurodegenerative disease."

Pop Test Oncology/Palisades Therapeutics invites industry leaders in the field of neuroscience such as Biogen Inc. BIIB; Johnson & Johnson JNJ; and Astra Zeneca PLC AZN to review our data.

Randi Altschul
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