Objective: To evaluate the efficacy and safety of NDM-101 as an adjunct to levodopa in reducing OFF-time, improving motor function, and maintaining quality of life without exacerbating dyskinesia in PD patients.

Background: Levodopa remains the most effective treatment for Parkinson’s disease (PD), yet its long-term use is limited by motor fluctuations and levodopa-induced dyskinesia (LID) (Olanow et al., 2013). Dopamine agonists reduce OFF-time but often exacerbate LID (Espay & Lang, 2017). NDM-101, a novel dopaminergic modulator, has been developed to enhance dopaminergic signaling while reducing OFF-time without increasing dyskinesia.

Method: A multicenter, double-blind, placebo-controlled trial enrolled 150 PD patients (Hoehn & Yahr Stages 2-3) with motor fluctuations. Subjects were randomized (1:1) to receive:

• NDM-101 (20 mg/day) + standard levodopa therapy

• Placebo + standard levodopa therapy

Primary Outcomes:

 – Change in Unified Parkinson’s Disease Rating Scale (UPDRS-III) for motor function

–  Daily OFF-time reduction (hours/day)

Secondary Outcomes:

 – Dyskinesia severity (UDysRS scores)

 – Quality of Life (PDQ-39 scores)

– Non-motor symptoms (NMSS total score)

Statistical analysis used repeated-measures ANOVA and multivariate regression to adjust for confounders (Poewe et al., 2017).

Results: Baseline Characteristics: No significant differences between groups (Table 1).

Motor Function: Patients receiving NDM-101 showed a 38% greater improvement in UPDRS-III scores compared to placebo (p < 0.001) (Figure 1) (Olanow et al., 2013).

OFF-Time Reduction: NDM-101 reduced OFF-time by 2.7 hours/day, while placebo led to a 0.9-hour reduction (mean difference 1.8 hours, p = 0.002) (Figure 2) (Espay & Lang, 2017).

Dyskinesia Analysis: Unlike dopamine agonists, NDM-101 did not increase dyskinesias, with UDysRS scores remaining stable (p = 0.31) (Figure 3) (Stocchi & Torti, 2016).

Quality of Life & Non-Motor Symptoms: The NDM-101 group showed significant improvement in PDQ-39 and NMSS total scores (p < 0.005) (Table 2) (Conn et al., 2005).

Conclusion: NDM-101 significantly improved motor function, reduced OFF-time, and maintained quality of life without worsening dyskinesia. These findings highlight NDM-101 as a promising adjunct therapy for PD patients experiencing motor fluctuations. Further long-term studies are warranted.

Baseline Characteristics (Methods section)

PDQ-39 & NMSS scores (Results section)

between groups (Results section)

in treatment vs. placebo (Results section)

UPDRS-Ill improvement over time (Results section)

References: Olanow CW, Kieburtz K, Rascol O, et al. Levodopa in the treatment of Parkinson’s disease: current controversies. Mov Disord. 2013;28(7):780-789.
2. Espay AJ, Lang AE. Common myths in levodopa therapy: debunking the “levodopa phobia.” Mov Disord Clin Pract. 2017;4(5):677-685.
3. Poewe W, Seppi K, Tanner CM, et al. Parkinson’s disease. Nat Rev Dis Primers. 2017;3(1):17013.
4. Stocchi F, Torti M. Adjuvant therapies for Parkinson’s disease: current status and future prospects. Mov Disord. 2016;31(9):1279-1291.
5. Conn PJ, Battaglia G, Marino MJ, et al. Modulating metabotropic glutamate receptors for Parkinson’s disease therapy: new perspectives. Nat Rev Drug Discov. 2005;4(12):1003-1013.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-novel-dopaminergic-modulator-ndm-101-as-an-adjunct-to-levodopa-enhancing-motor-control-without-worsening-dyskinesia-in-parkinsons-disease/