Vaccines · 2026
A Case Report of a Novel Alpha-Synuclein Vaccine (TRB-001) in a Parkinson's Patient: Safe Administration and Induction of a High-Titer, High-Avidity Functional Antibody Response.
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Volc Dieter, Thun-Hohenstein Caroline, Schmidhuber Sabine, Mandler Markus, Schneeberger Achim
Аннотация
BACKGROUND/OBJECTIVES: Parkinson's disease (PD) is a major neurodegenerative disorder with no cure. The goal is to develop an active immunotherapy targeting aggregated alpha synuclein (aSyn), the root cause of PD. TRB-001 is the lead candidate of a novel class of vaccines. It is a peptide/protein conjugate coupled to sugar residues, which is used to target and activate antigen-presenting cells, and addresses aSyn.
METHODS: A 33-year-old male, diagnosed with PD seven years previously, with a Hoehn & Yahr stage of 1, taking Levodopa/Benserazide (100/25 mg, 6× per day), Rotigotine (8 mg) and Rasagiline (1 mg), amounting to a Levodopa equivalent daily dose (LEDD) of 940 mg, also complicated by impulse control disorder, requested experimental therapy. He received a total of four TRB-001 administrations (weeks 0, 4, 8 and 34) following informed consent. The workup included safety, immunological and clinical parameters.
RESULTS: Vaccinations were well tolerated. They induced a high-titer aSyn-specific antibody (Ab) response. Titer increase was associated with a reduction in aSyn plasma levels, suggesting target engagement. The Ab titer and the reduction in aSyn plasma levels were both long-lived. The boost elicited a recall-type Ab titer increase and triggered avidity maturation (factor 7.8). Abs demonstrated a high degree of selectivity for aggregated aSyn (factor 30). Moreover, they were found to preferentially react with tissue from PD brain lysates. The Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score for the patient remained essentially stable throughout the observation period of 53 weeks. At the time of the boost, the symptomatic PD therapy was simplified to Levodopa/Carbidopa/Entacapone 100/25/200 mg four times a day, amounting to an LEDD of 532 mg. This put an end to the symptoms of the impulse control disorder.
CONCLUSIONS: Results obtained suggest that this new class of vaccines may yield Ab responses comparable in magnitude and target avidity to the therapeutic setting of monoclonal Abs. TRB-001 is currently being translated to a randomized, placebo-controlled Phase 1B study.
METHODS: A 33-year-old male, diagnosed with PD seven years previously, with a Hoehn & Yahr stage of 1, taking Levodopa/Benserazide (100/25 mg, 6× per day), Rotigotine (8 mg) and Rasagiline (1 mg), amounting to a Levodopa equivalent daily dose (LEDD) of 940 mg, also complicated by impulse control disorder, requested experimental therapy. He received a total of four TRB-001 administrations (weeks 0, 4, 8 and 34) following informed consent. The workup included safety, immunological and clinical parameters.
RESULTS: Vaccinations were well tolerated. They induced a high-titer aSyn-specific antibody (Ab) response. Titer increase was associated with a reduction in aSyn plasma levels, suggesting target engagement. The Ab titer and the reduction in aSyn plasma levels were both long-lived. The boost elicited a recall-type Ab titer increase and triggered avidity maturation (factor 7.8). Abs demonstrated a high degree of selectivity for aggregated aSyn (factor 30). Moreover, they were found to preferentially react with tissue from PD brain lysates. The Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score for the patient remained essentially stable throughout the observation period of 53 weeks. At the time of the boost, the symptomatic PD therapy was simplified to Levodopa/Carbidopa/Entacapone 100/25/200 mg four times a day, amounting to an LEDD of 532 mg. This put an end to the symptoms of the impulse control disorder.
CONCLUSIONS: Results obtained suggest that this new class of vaccines may yield Ab responses comparable in magnitude and target avidity to the therapeutic setting of monoclonal Abs. TRB-001 is currently being translated to a randomized, placebo-controlled Phase 1B study.