scholarly journals Safety and Tolerability of Active Immunotherapy Targeting α-Synuclein with PD03A in Patients with Early Parkinson’s Disease: A Randomized, Placebo-Controlled, Phase 1 Study

2021 ◽  
pp. 1-11
Author(s):  
Werner Poewe ◽  
Dieter Volc ◽  
Klaus Seppi ◽  
Rossella Medori ◽  
Petra Lührs ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Antibody Response ◽  
Phase 1 ◽  
Booster Vaccination ◽  
Active Immunotherapy ◽  
Igg Antibody ◽  
Phase 1 Study ◽  
Positive Antibody ◽  
Secondary Objective

Background: Immunotherapies targeting α-synuclein aim to limit its extracellular spread in the brain and prevent progression of pathology in Parkinson’s disease (PD). PD03A is a specific active immunotherapy (SAIT) involving immunization with a short peptide formulation. Objective: This phase 1 study characterized the safety and tolerability of PD03A in patients with early PD. A key secondary objective was to evaluate immunological activity following immunization. Methods: This was a phase 1 study of two different doses of PD03A versus placebo in PD patients. Patients were randomized (1:1:1) to receive four priming plus one booster vaccination of PD03A 15μg, PD03A 75μg or placebo and were followed for 52 weeks. Results: Overall, 36 patients were randomized, of which 35 received five immunizations and completed the study. All patients experienced at least one adverse event. Transient local injection site reactions affected all but two patients; otherwise most AEs were considered unrelated to study treatment. A substantial IgG antibody response against PD03 was observed with a maximum titer achieved at Week-12. Differences in titers between both active groups versus placebo were statistically significant from the second immunization at Week-8 until Week-52. Conclusion: The safety profile and positive antibody response of PD03A supports the further development of active immunotherapeutic approaches for the treatment of PD.

scholarly journals Long-Term Evaluation of a Phase 1 Study of AADC Gene Therapy for Parkinson's Disease

2012 ◽  
Vol 23 (4) ◽  
pp. 377-381 ◽  
Author(s):  
Gabriele Mittermeyer ◽  
Chadwick W. Christine ◽  
Kathryn H. Rosenbluth ◽  
Suzanne L. Baker ◽  
Philip Starr ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Phase 1 ◽  
Phase 1 Study ◽  
Term Evaluation

scholarly journals Evaluation of smartphone-based testing to generate exploratory outcome measures in a phase 1 Parkinson's disease clinical trial

2018 ◽  
Vol 33 (8) ◽  
pp. 1287-1297 ◽  
Author(s):  
Florian Lipsmeier ◽  
Kirsten I. Taylor ◽  
Timothy Kilchenmann ◽  
Detlef Wolf ◽  
Alf Scotland ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Clinical Trial ◽  
Parkinson's Disease ◽  
Outcome Measures ◽  
Phase 1

scholarly journals Evaluation of the safety and immunomodulatory effects of sargramostim in a randomized, double-blind phase 1 clinical Parkinson’s disease trial

2017 ◽  
Vol 3 (1) ◽  
Author(s):  
Howard E. Gendelman ◽  
Yuning Zhang ◽  
Pamela Santamaria ◽  
Katherine E. Olson ◽  
Charles R. Schutt ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Clinical Investigation ◽  
Phase 1 ◽  
Additional Patient ◽  
Double Blind ◽  
Modest Improvement ◽  
Cell Counts ◽  
Study Results

Abstract A potential therapeutic role for immune transformation in Parkinson’s disease evolves from more than a decade of animal investigations demonstrating regulatory T cell (Treg) nigrostriatal neuroprotection. To bridge these results to human disease, we conducted a randomized, placebo-controlled double-blind phase 1 trial with a well-studied immune modulator, sargramostim (granulocyte-macrophage colony-stimulating factor). We enrolled 17 age-matched non-Parkinsonian subjects as non-treated controls and 20 Parkinson’s disease patients. Both Parkinson’s disease patients and controls were monitored for 2 months for baseline profiling. Parkinson’s disease patients were then randomized into two equal groups to self-administer placebo (saline) or sargramostim subcutaneously at 6 μg/kg/day for 56 days. Adverse events for the sargramostim and placebo groups were 100% (10/10) and 80% (8/10), respectively. These included injection site reactions, increased total white cell counts, and upper extremity bone pain. One urticarial and one vasculitis reaction were found to be drug and benzyl alcohol related, respectively. An additional patient with a history of cerebrovascular disease suffered a stroke on study. Unified Parkinson’s disease rating scale, Part III scores in the sargramostim group showed modest improvement after 6 and 8 weeks of treatment when compared with placebo. This paralleled improved magnetoencephalography-recorded cortical motor activities and Treg numbers and function compared with pretreated Parkinson’s disease patients and non-Parkinsonian controls. Peripheral Treg transformation was linked to serum tryptophan metabolites, including L-kynurenine, quinolinic acid, and serotonin. These data offer a potential paradigm shift in modulating immune responses for potential therapeutic gain for Parkinson’s disease. Confirmation of these early study results requires larger numbers of enrolled patients and further clinical investigation.

Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial

The Lancet ◽  
2014 ◽  
Vol 383 (9923) ◽  
pp. 1138-1146 ◽  
Author(s):  
Stéphane Palfi ◽  
Jean Marc Gurruchaga ◽  
G Scott Ralph ◽  
Helene Lepetit ◽  
Sonia Lavisse ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Dose Escalation ◽  
Lentiviral Vector ◽  
Phase 1 ◽  
Open Label ◽  
Open Label Phase

scholarly journals Control and Preventive Study of Brucellosis by Using

2017 ◽  
Vol 3 (6) ◽  
pp. 234
Author(s):  
Rahmahani J ◽  
Handijatno D ◽  
Tyaningsih W ◽  
Suwarno Suwarno
Keyword(s):  
Immune Response ◽  
Sodium Chloride ◽  
Antibody Response ◽  
Brucella Abortus ◽  
Cellular Response ◽  
Booster Vaccination ◽  
Humoral Response ◽  
Igg Antibody ◽  
Whole Cells ◽  
Cellular Immune

The aims of this research is to determine the ability of sub unit lipopolysacharide(LPS) vaccine of Brucella abortus strain S-19 in mice and goat, including IgM and sub classes IgG antibody humoral response, cellular mediated immune response (IL-2, IFN- γ) in mice, also IgG as humoral immunity, IL-4 and IL-12 as cellular immunity, comparison affectivity with Brucella abortus strain RB-51 vaccine in goat . This research has two steps methods. Step first, 30 Balb C mice were divided into 3 groups and vaccinated subcutaneously, First group injectedB. abortus S-19, second group injected LPS and third group injected sodium chloride solution. Booster vaccination was conducted every two weeks till the eight week after first vaccination. The second step performed vaccinated to 30 goats divided into three groups. First group was injected by subcutaneous LPS 50 µg/ml and second group injected LPS 100 µg/ml and the third group injected with sodium chloride as control. Booster vaccination conducted 2 weeks after first vaccination and second vaccination. Result of the research conferred. Result research, antibody response in mice showed vaccination by LPS of B. abortus S-19 showed higher titer than vaccination by whole cells but inverse cellular response. The both vaccines showed induce subclass antibody response, vaccination by LPS tendency to IgM response but vaccination by Whole cells active vaccine tendency to IgG1, IgG 2a and IgG2b. Response antibody in goat on two weeks after first vaccination, vaccination with LPS of B. abortus S-19, dose 50 µg/ml failed or zero titer IgG response but dose 100 µg/ml was 500response antibody on two weeks after second vaccination by dose 50 µg/ml was 340 but by dose 100 µg/ml was 960, while cellular IL-12 response two weeks after first vaccination by dose 50 µg/ml was 22.88 pg/ml but by 100 µg/ml was 62.15 pg/ml. Response cellular IL -12 two weeks after second vaccination 50 µg/ml was 12.04 pg/ml while by dose100 µg/ml was 130.88pg/ml    Cellular immune response IL-4 on two weeks after first vaccination, dose 50 µg/ml showed 55.57 pg/ml but by dose100 µg/ml was 49.35 pg/ ml. Response cellular IL-4 on two weeks after second vaccination by dose 50 µg/ml  was 22.17 pg/ml but by dose 100 µg/ml was 143.89 pg/ml Keyword: Vaccine sub-unit LPS of Brucella abortus S-19, Humoral antibody, Cellular antibody

scholarly journals Magnetic resonance imaging–guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease

2019 ◽  
Vol 85 (5) ◽  
pp. 704-714 ◽  
Author(s):  
Chadwick W. Christine ◽  
Krystof S. Bankiewicz ◽  
Amber D. Van Laar ◽  
R. Mark Richardson ◽  
Bernard Ravina ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Magnetic Resonance ◽  
Phase 1 ◽  
Resonance Imaging ◽  
Phase 1 Trial

scholarly journals Parkinson’s Disease Drug Development Since 1999: A Story of Repurposing and Relative Success

2021 ◽  
pp. 1-9
Author(s):  
Deirdre M. Boucherie ◽  
Gonçalo S. Duarte ◽  
Tiago Machado ◽  
Patrícia R. Faustino ◽  
Cristina Sampaio ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Development ◽  
Success Rate ◽  
Phase 1 ◽  
Phase 2 ◽  
Development Programs ◽  
Inclusion Criteria ◽  
Phase 3 ◽  
Heterogeneous Nature

Background: A global overview of drug development programs in Parkinson’s disease over the last few decades is lacking, while such programs are challenging given the multifaceted and heterogeneous nature of the disease. Objective: To indirectly assess drug development programs in Parkinson’s disease, exploring some factors associated with compound attrition at different trial phases. Methods: We assessed all Parkinson’s disease trials in the WHO trials portal, from inception (1999) to September 2019. Independent authors selected trials and extracted data. The success rate was the number of compounds that progressed to the next drug development phase divided by the number of compounds in that phase. Results: Overall, 357 trials (studying 152 compounds) fulfilled our inclusion criteria, with 62 (17.3%) phase 1 trials, 135 (37.8%) phase 2 trials, 85 (23.8%) phase 3 trials, and 53 (14.8%) phase 4 trials. The success rate was 42.4% from phase 2 to 3. Original compounds received regulatory approval by the FDA in 21.4% of cases, compared with 6.7% of repurposed compounds, representing an overall success rate of 14.9%. We found 172 trials (48.2%) conducted for repurposing previously licensed compounds. These figures were approximately the same regarding approval by the EMA. Most compounds were approved to treat parkinsonism and motor fluctuations. Conclusion: We found a moderate-to-high success rate in all phases of drug development. This was largely based on the success of original compounds, despite almost half of the identified trials attempting compound repurposing.

scholarly journals Phase 1 Parkinson’s Disease Studies Show the Dopamine D1/D5 Agonist PF-06649751 is Safe and Well Tolerated

2018 ◽  
Vol 7 (2) ◽  
pp. 307-319 ◽  
Author(s):  
U. Shivraj Sohur ◽  
David L. Gray ◽  
Sridhar Duvvuri ◽  
Yao Zhang ◽  
Kathleen Thayer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Phase 1

Safety and immunogenicity of the α-synuclein active immunotherapeutic PD01A in patients with Parkinson's disease: a randomised, single-blinded, phase 1 trial

2020 ◽  
Vol 19 (7) ◽  
pp. 591-600 ◽  
Author(s):  
Dieter Volc ◽  
Werner Poewe ◽  
Alexandra Kutzelnigg ◽  
Petra Lührs ◽  
Caroline Thun-Hohenstein ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Phase 1 ◽  
Phase 1 Trial
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