Parkinson’s is among the fastest-growing neurodegenerative conditions

Global prevalence is predicted to double by 2050. Currently, there are no treatments available that slow or halt disease progression; existing medicines provide only temporary symptomatic relief.

Disease pathology: inherited mutations and toxic α-synuclein oligomers

In Parkinson’s, inherited mutations and toxic α-synuclein disrupt mitochondrial calcium 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. 1,2,3

The mPTP opening is linked to the pathophysiology in Parkinson’s

NRG5051, our lead clinical asset, is a potent inhibitor of the mPTP, acting via a novel NLRX1-mediated disease-modifying mechanism-of-action, that protects mitochondrial function and prevents neuronal death.

NRG5051 Parkinson’s preclinical studies

In preclinical Parkinson’s models NRG5051 inhibits α-synuclein oligomer-induced mPTP opening, 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