Monoclonal antibody placinezumab shows potential to slow rapid progression of Parkinson's disease

In a recent study published in the journal natural medicine, a large international research team is investigating whether the monoclonal antibody plasinezumab, previously observed to be effective in slowing the progression of movement-related symptoms in Parkinson's disease, actually shows effects in subgroups of Parkinson's disease. We conducted an exploratory analysis to assess whether Patients with rapid progression of motor degeneration.

study: Placinezumab slows motor progression in rapidly progressive early Parkinson's disease. Image credit: Naeblys / Shutterstock

background

A hallmark of Parkinson's disease is the aggregation of α-synuclein, which is thought to propagate between neurons and contribute to the onset of Parkinson's disease. One of the first treatment options to target aggregated alpha-synuclein was the monoclonal antibody placinezumab, which was studied in a phase II clinical trial in patients with early Parkinson's disease who participated in the PASADENA trial.

The primary endpoint of the Phase II PASADENA study was the Movement Disorder Society Unified Parkinson's Disease Rating Scale or MDS-UPDRS score. Although the monoclonal antibody was not found to be effective along all parameters of her MDS-UPDRS, patients who received plasinezumab had less progression of exercise-related degeneration compared to patients treated with placebo. It was shown to be slow. Additionally, the team also believed that the MDS-UPDRS subscales were unlikely to show change over short observation periods such as one year.

About research

In this study, the team investigated the effect of placinezumab on slowing the progression of motor degeneration in a subgroup of patients with rapidly progressive Parkinson's disease. Considering that the MDS-UPDRS subscales may not show short-term treatment-related changes, looking at rapidly progressing Parkinson's disease subgroups could help improve the signal-to-noise ratio. It may reveal the potential efficacy of monoclonal antibody therapy.

The PASADENA trial consisted of three treatments: placebo, 1,500 mg plasinezumab, and 4,500 mg plasinezumab. Patients were stratified by age (older or younger than 60 years), gender, and use of monoamine oxidase B inhibitors, and then randomly assigned to three groups. Patients using other symptomatic Parkinson's disease medications such as dopamine agonists or levodopa at baseline were excluded. If the use of these drugs was considered mandatory, the MDS-UPDRS score was calculated before starting treatment.

This study investigated the effects of plasinezumab in patients who were on stable doses of monoamine oxidase B inhibitors at baseline and who had other indicators of rapid disease progression. Analyzes of the six major prespecified subpopulations included in Phases I and II of the PASADENA study included results from only four subpopulations.

Subpopulations differed by monoamine oxidase B inhibitor use, Parkinson's disease stage 2 or Horn-Yarl stage and stage 1, those with and without REM or rapid eye movement sleep behavior disorder, and diffuse malignant phenotypes and those without. It was based on the use of a diffuse malignant phenotype.

This analysis also divided into six exploratory subpopulations based on age, gender, disease duration, age at diagnosis, and motor subphenotypes such as tremor-dominant versus akinetic rigidity or postural instability gait dysfunction. stratified along. Additionally, his two treatment groups consisting of 1,500 mg and 4,500 mg plasinezumab were pooled for analysis, as previous studies did not report a dose response.

result

The study results suggested that placinezumab was more effective in slowing the progression of motor signs in patients with rapidly progressive Parkinson's disease. Subpopulation analysis revealed that patients with a diffuse malignant phenotype or those who were on monoamine oxidase B inhibitors at baseline, which is indicative of rapid disease progression, were compared with patients with a phenotype that does not indicate rapid progression. showed that the signs of exercise-related degeneration were delayed compared to Progression of Parkinson's disease.

MDS-UPDRS Part III scores corresponding to clinician-rated motor signs showed that patients treated with plasinezumab experienced a slower increase or worsening of degeneration than patients treated with placebo. Parts I and II of the MDS-UPDRS score correspond to patient-reported motor and non-motor signs, respectively.

Researchers believe that changes in Part III or clinician-assessed motor signs from Parts I and II, as data show faster progression along MDS-UPDRS Part III compared to Parts I and II. We believe that there is a possibility that it will lead to These findings also indicate that longer observation periods are required to accurately assess the potential efficacy of treatments such as plasinezumab.

conclusion

Overall, the results suggested that the monoclonal antibody plasinezumab could be used to slow the progression of movement-related degeneration in patients with rapidly progressive Parkinson's disease. Additionally, longer observation periods are required to observe the impact of plasinezumab treatment in patients with slowly progressive disease. Furthermore, additional randomized clinical trials are required to further validate these findings.