Category: Parkinson’s Disease: Clinical Trials
Objective: Evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TT-P34 in cerebrospinal fluid (CSF) following multiple subcutaneous (SC) doses in Parkinson’s disease patients and confirm previous safety profile and CSF exposure generated in healthy participants.
Background: Parkinson’s disease, and dementia with Lewy bodies are characterized by synaptic loss and neuronal dysfunction, driven in part by impaired cyclic AMP response element-binding protein (CREB) signalling. TT-P34 is a novel investigational compound designed to specifically restore neuronal CREB activity and thereby promoting lysosomal biogenesis and neurotrophic support. TT-P34 is a cyclic peptide optimized for once weekly SC administration. The drug was proven to be safe, well tolerated and has reached sufficient CSF exposure in healthy participants after single and multiple dosing.
Method: A randomized, double-blind, placebo-controlled Phase I trial was conducted at the Centre for Human Drug Research, Leiden, the Netherlands. The study included one multiple dosing cohort of Parkinson’s disease patients to confirm safety, CSF PK profiling, and exploratory CSF biomarkers linked to CREB activity and lysosomal function. TT-P34 was administered SC once weekly for 4 weeks. CSF was collected as baseline, after the last dose (Day 22) and 28 days later (Day 50).
Results: At the time of abstract submission, the study completed enrolment. Dosing was successfully completed in 5/12. No relevant AEs had been reported by that time, and all SC injections were well tolerated.
Conclusion: TT-P34 is the first lysosomal enhancer in clinical development that is working via restoring intracellular CREB signalling. This represents a new class of therapeutics for neurodegenerative diseases. Phase I clinical data from healthy participants confirm that TT-P34 is safe and qualified for advancement into later stages of development. This investigation in Parkinson’s disease patients is relevant for defining a safe and biologically effective dose for future development and investigate target engagement biomarker in CSF.
To cite this abstract in AMA style:
A. Borta, K. Comassi, S. Singh, E. Browne, A. Dalby, S. Korsten, M. Aaboe Jørgensen, G. Layton, J. Castricum, S. Mølgaard, P. Kremer. Clinical Evaluation of TT-P34: Exploring Safety and CSF Exposure in Parkinson’s Disease Patients [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/clinical-evaluation-of-tt-p34-exploring-safety-and-csf-exposure-in-parkinsons-disease-patients/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-evaluation-of-tt-p34-exploring-safety-and-csf-exposure-in-parkinsons-disease-patients/