ArticleBritish journal of clinical pharmacology2021
A randomized single and multiple ascending dose study in healthy volunteers of LTI-291, a centrally penetrant glucocerebrosidase activator.
Article in British journal of clinical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- A Systematic Review on Disease-Modifying Therapies in Parkinsonian Disorders.Clinical pharmacology and therapeutics · 2026Pooled it
- Interplay of GBA1 with lysosomal dysfunction and inflammation in Parkinson's disease.Neural regeneration research · 2026Article
- Pathological Protein Targets in Parkinson's Disease: Progress Towards the Development of Disease-Modifying Therapies.CNS drugs · 2026Review
- The Race to Salvage Glucocerebrosidase: Understanding Small-Molecule Therapies for GBA1-Associated Parkinsonism.Movement disorders : official journal of the Movement Disorder Society · 2026Review
- High-throughput screening for small-molecule stabilizers of misfolded glucocerebrosidase in Gaucher disease and Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Development of Tunable Mechanism-Based Carbasugar Ligands that Stabilize Glycoside Hydrolases through the Formation of Transient Covalent Intermediates.ACS catalysis · 2024Article
- Lysosomal dysfunction in α-synuclein pathology: molecular mechanisms and therapeutic strategies.Cellular and molecular life sciences : CMLS · 2024Review
- Activation and Purification of ß-Glucocerebrosidase by Exploiting its Transporter LIMP-2 - Implications for Novel Treatment Strategies in Gaucher's and Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Development of quantitative high-throughput screening assays to identify, validate, and optimize small-molecule stabilizers of misfolded β-glucocerebrosidase with therapeutic potential for Gaucher disease and Parkinson's disease.bioRxiv : the preprint server for biology · 2024Article
- Inhibition of cysteine protease cathepsin L increases the level and activity of lysosomal glucocerebrosidase.JCI insight · 2024Article
- International Genetic Testing and Counseling Practices for Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2023Article
- Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy.Pharmaceutics · 2023Review
- iPSC-derived neural precursor cells engineeringMolecular therapy. Methods & clinical development · 2023Article
- Parkinson's disease therapy: what lies ahead?Journal of neural transmission (Vienna, Austria : 1996) · 2023Review
- Review
- Recent Advances in Drug Therapy for Parkinson's Disease.Internal medicine (Tokyo, Japan) · 2023Review
- Targeting protein clearance pathways inExpert opinion on therapeutic targets · 2022Article
- Precision Medicine in Parkinson's Disease: From Genetic Risk Signals to Personalized Therapy.Brain sciences · 2022Review
- Glucocerebrosidase mutations and Parkinson disease.Journal of neural transmission (Vienna, Austria : 1996) · 2022Review
- Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models.Autophagy · 2022Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsA mutation in the GBA1 gene is the most common genetic risk factor for developing Parkinson's disease. GBA1 encodes the lysosomal enzyme glucosylceramidase beta (glucocerebrosidase, GCase) and mutations decrease enzyme activity. LTI-291 is an allosteric modulator of GCase, enhancing its activity. These first-in-human studies evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of LTI-291 in healthy volunteers.
methodsIn the single ascending dose (SAD) study, 40 healthy volunteers were randomly assigned to LTI-291 (n = 8 per dose level) or placebo (n = 2 per dose level). Single doses of 3, 10, 30 and 90 mg LTI-291 were investigated. In the multiple ascending dose (MAD) study, 40 healthy middle-aged or elderly volunteers were randomly assigned to LTI-291 (n = 8 per dose level) or placebo (n = 2 per dose level). Fourteen consecutive daily doses of 3, 10, 30 and 60 mg LTI-291 or placebo were administered. In both the SAD and MAD studies, glycosphingolipid levels were measured and a test battery of neurocognitive tasks was performed.
resultsLTI-291 was generally well tolerated and no deaths or treatment-related SAEs occurred and no subject withdrew from a study due to AEs. C
conclusionsThese first-in-human studies demonstrated that LTI-291 was well tolerated when given orally once daily for 14 consecutive days. This supports the continued clinical development and the exploration of LTI-291 effects in a GBA1-mutated Parkinson population.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.