Parkinson’s and NRG5051 disease-modifying MOA

Parkinson’s is among the fastest-growing neurodegenerative conditions, with global prevalence predicted to double by 2050. No current treatments slow or halt disease progression; existing medicines provide only temporary symptomatic relief.

Inherited mutations and toxic α-synuclein oligomers

In Parkinson’s, inherited mutations and toxic ⍺-synuclein disrupt Ca2+ homeostasis, leading to mitochondrial dysfunction and mPTP opening in dopaminergic substantia nigra neurons. This drives bioenergetic deficits, oxidative stress and neuroinflammation, ultimately contributing to neuronal death and disease progression. 2,3,4

NRG5051 Parkinson’s preclinical studies

In preclinical Parkinson’s models NRG5051 inhibits ⍺-synuclein oligomer-induced mPTP opening, reduces neuroinflammation, protects neurons and improves motor function.

Compelling preclinical data support NRG5051’s advancement into human clinical trials as a potential treatment for Parkinson’s.

References

  1. α-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson’s disease: Ludtmann et al., 2018, Nature Communications, 9, 1-16
  2. The Origins of Oxidant Stress in Parkinson’s Disease and Therapeutic Strategies. Surmeier et al., 2011, Antioxidants & Redox Signaling 14, 289-1301.
  3. Mitochondrial permeability transition pore regulates Parkinson’s disease development in mutant α-synuclein transgenic mice. Martin et al., 2014, Neurobiology of Aging 35,1132-52