We have successfully established stable and effective models of Parkinson's disease (PD) in both rhesus and cynomolgus monkeys, which can be utilized for drug efficacy evaluations, stem cell therapy assessments, and other research areas, demonstrating significant preclinical application value. In our PD models, we observed a notable loss of dopaminergic neuronal projections in the caudate and putamen, confirmed by DAT PET scans seven days post-modeling, alongside various Parkinsonian behavioral changes. These non-human primate (NHP) models exhibited stable Parkinsonian behaviors for over 12 months, characterized by a high success rate in dopaminergic neuron loss and low mortality.

●PD Model of Rhesus Monkey

1. Development and Pharmacological Validation of the MPTP-Induced PD Rhesus Monkey Model 

During the modeling period, the Kurlan score of experimental monkeys gradually increased, with variability in the time taken for different individuals to reach a score of 15, indicating they have researched severe stage, and persisted for at least 64 weeks, underscoring the stability of our model. L-DOPA, the first-line treatment for PD, is known to elevate dopamine levels in the brain. As illustrated in Figure 1, MPTP significantly raised the Kurlan score, reflecting severe motor impairment. Within one hour post-L-DOPA administration, there was a rapid and significant decrease in the Kurlan score, alleviating PD symptoms and confirming the successful establishment of the PD monkey model.

Figure 1

2.MPTP induced L-dopa reversible fine motor dysfunction of upper limbs

Post-modeling, the time required for PD rhesus monkeys to grasp food significantly increased, indicating marked deterioration in fine motor skills. Following L-DOPA treatment, the time to grasp food returned to pre-modeling levels, and fine motor function in the fingers improved rapidly (Figure 2).

Figure. 2

●PD Model of Cynomolgus Monkey

MPTP induced the construction of PD cynomolgus monkey model

1.MPTP Induced PD Model of Cynomolgus Monkey

Kurlan scores in cynomolgus monkeys rose progressively during MPTP administration. Post-modeling, these scores remained consistently high (≥15) for at least 8 weeks, indicating the stablility of PD.( Figure. 3)

Figure. 3

2.MPTP induced fine motor dysfunction of upper limbs

Compared to measurements before  modeling, the time required for PD cynomolgus monkeys to grasp food significantly increased, highlighting a severe decline in upper limb fine motor skills (Figure 4).

Figure. 4