Development of PTI-125-DX, a blood-based diagnostic for Alzheimer's disease
开发阿尔茨海默病的血液诊断剂 PTI-125-DX
基本信息
- 批准号:9758123
- 负责人:
- 金额:$ 110.97万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-30 至 2020-06-30
- 项目状态:已结题
- 来源:
- 关键词:AffinityAgeAllelesAlzheimer&aposs DiseaseAlzheimer’s disease biomarkerAmyloid beta-ProteinAntibodiesAntibody FormationAntigensArchivesAutopsyBindingBiological AssayBlindedBloodBrainBrain DiseasesClinical TrialsDementiaDependenceDetectionDevelopmentDiagnosisDiagnosticDiagnostic testsDiseaseDot ImmunoblottingEarly Onset Familial Alzheimer&aposs DiseaseElderlyEnzyme-Linked Immunosorbent AssayEpitopesFrontotemporal DementiaGenotypeHippocampus (Brain)HybridomasImageImmune SeraImmunizeImmunoglobulin GInstitutional Review BoardsLeadLengthLewy Body DementiaMalignant NeoplasmsMeasuresMolecular ConformationMonoclonal AntibodiesMusMutationNeurobehavioral ManifestationsOryctolagus cuniculusPainParkinson DiseasePathologicPathologyPatientsPeptide FragmentsPeptidesPhasePlasmaPositron-Emission TomographyProductionProtein FragmentProtocols documentationRecombinant ProteinsRecombinantsSamplingSliceSmall Business Technology Transfer ResearchSpecificityTestingTherapeuticTimeTissuesWestern BlottingWorkalpha-bungarotoxin receptorbaseclinical Diagnosiscommercializationcompanion diagnosticsdiagnostic biomarkerdisease diagnosisfilaminfluorodeoxyglucose positron emission tomographyhyperphosphorylated tauinterestmild cognitive impairmentmonoclonal antibody productionnovelpolyclonal antibodypreventsmall molecule therapeuticstau Proteinstherapeutic candidate
项目摘要
Abstract
PTI is developing PTI-125-DX, a novel, quantitative blood-based diagnostic candidate for
Alzheimer's disease (AD). A non-invasive and inexpensive AD diagnostic is sorely needed,
particularly one with the ability to detect early pathological changes that precede cognitive
symptoms. PTI-125-DX measures the ratio of two protein fragments in plasma and is a
companion diagnostic/biomarker for our therapeutic candidate PTI-125. PTI-125 disrupts and
prevents filamin A (FLNA)'s association with the α7-nicotinic acetylcholine receptor (α7nAChR),
which amyloid beta 1-42 (Aβ42) hijacks to hyperphosphorylate tau protein. We have tested over
220 plasma samples and show two orders of magnitude significant differences between patients
with AD diagnoses (confirmed by imaging or CSF markers) and age-matched normal controls.
These two groups are distinguished with 98-100% accuracy. In one of two blinded studies, PTI-
125-DX distinguished MCI with confirmed AD pathology (MCI-AD) from MCI with suspected non-
amyloid pathology (MCI-SNAP) with 92% accuracy; in the other, this distinction needs
confirmation by imaging. In this proposal, we will compare additional MCI-AD and MCI-SNAP
samples and determine disease specificity of the assay by testing archived plasma samples from
patients with dementia with Lewy bodies, Frontotemporal Dementia and Parkinson's disease
alongside AD, MCI-AD, MCI-SNAP, early-onset familial AD (FAD), cancer and elderly or young
controls. As PTI-125-DX is currently in Western blot format, we will develop an ELISA assay and
compare it to an automated Western blot format using ProteinSimple's Wes™. In Phase II, we will
generate proprietary antibodies by immunizing with carefully selected peptides and recombinant
proteins; these polyclonal antibodies will be screened and tested to determine optimal
combinations. The corresponding immunogens will then be used to develop monoclonal
antibodies. The sandwich ELISA we envision will capture all fragments of interest and separately
detect two specific protein fragments. With final monoclonal antibodies and a final ELISA (or Wes)
format selected, we will perform a new blinded study of up to 250 de-identified plasma samples
from the AIBL study. At the conclusion of this work, PTI-125-DX will be ready for
commercialization or partnering.
摘要
PTI正在开发PTI-125-DX,这是一种新型的定量血液诊断候选药物,
阿尔茨海默病(AD)。迫切需要一种非侵入性且廉价的AD诊断方法,
特别是能够检测出认知障碍之前的早期病理变化的人,
症状PTI-125-DX测量血浆中两种蛋白质片段的比例,
我们的治疗候选物PTI-125的伴随诊断/生物标志物。PTI-125干扰和
阻止细丝蛋白A(FLNA)与α7-烟碱乙酰胆碱受体(α 7 nAChR)的结合,
淀粉样蛋白β 1-42(Aβ42)被劫持以过度磷酸化tau蛋白。我们已经测试了
220份血浆样本,并显示两个数量级的患者之间的显着差异
AD诊断(通过影像学或CSF标志物证实)和年龄匹配的正常对照。
这两个组的区分具有98-100%的准确性。在两项设盲研究之一中,PTI-
125-DX将具有确诊AD病理学的MCI(MCI-AD)与具有疑似非AD病理学的MCI区分开。
淀粉样蛋白病理学(MCI-SNAP)的准确率为92%;在另一个,这种区分需要
通过成像确认。在本提案中,我们将比较额外的MCI-AD和MCI-SNAP
样本,并通过检测来自以下样本的存档血浆样本来确定测定的疾病特异性:
路易体痴呆、额颞叶痴呆和帕金森病患者
与AD、MCI-AD、MCI-SNAP、早发性家族性AD(FAD)、癌症和老年人或年轻人一起
对照由于PTI-125-DX目前为蛋白质印迹形式,我们将开发ELISA测定法,
将其与使用ProteinSimple's Wes™的自动Western印迹格式进行比较。在第二阶段,我们将
通过用精心选择的肽和重组体免疫产生专有抗体,
这些多克隆抗体将被筛选和测试,以确定最佳的
组合。然后将相应的免疫原用于开发单克隆抗体。
抗体的我们设想的夹心ELISA将捕获所有感兴趣的片段,
检测两个特定的蛋白质片段。最终单克隆抗体和最终ELISA(或Wes)
选择格式后,我们将对多达250份去识别血浆样本进行新的设盲研究
来自Aibl研究。在这项工作结束时,PTI-125-DX将准备就绪,
商业化或合作。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Lindsay H Burns其他文献
Lindsay H Burns的其他文献
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{{ truncateString('Lindsay H Burns', 18)}}的其他基金
Food Effect study and drug supply scale-up for PTI-125
PTI-125 的食物效应研究和药物供应规模扩大
- 批准号:
10216906 - 财政年份:2021
- 资助金额:
$ 110.97万 - 项目类别:
Increasing size of Phase 2b clinical trial to 60 patients
2b 期临床试验规模扩大至 60 名患者
- 批准号:
10018305 - 财政年份:2018
- 资助金额:
$ 110.97万 - 项目类别:
IND, FIH study and 3-month tox for PTI-125, a novel therapeutic for Alzheimer's disease
PTI-125(一种阿尔茨海默病的新型疗法)的 IND、FIH 研究和 3 个月毒性
- 批准号:
9337906 - 财政年份:2017
- 资助金额:
$ 110.97万 - 项目类别:
Solid oral dosage form and chronic tox for PTI-125
PTI-125的固体口服剂型和慢性毒性
- 批准号:
9624887 - 财政年份:2017
- 资助金额:
$ 110.97万 - 项目类别:
Additional bioanalytical, dose analysis and DSMB costs for PTI-125 development
PTI-125 开发的额外生物分析、剂量分析和 DSMB 成本
- 批准号:
9524402 - 财政年份:2017
- 资助金额:
$ 110.97万 - 项目类别:
IND, FIH study and 3-month tox for PTI-125, a novel therapeutic for Alzheimer's disease
PTI-125(一种阿尔茨海默病的新型疗法)的 IND、FIH 研究和 3 个月毒性
- 批准号:
9541054 - 财政年份:2017
- 资助金额:
$ 110.97万 - 项目类别:
IND- and NDA-enabling toxicology studies for PTI-125, a novel small molecule for Alzheimer's disease
PTI-125(一种治疗阿尔茨海默病的新型小分子)的 IND 和 NDA 毒理学研究
- 批准号:
9186714 - 财政年份:2015
- 资助金额:
$ 110.97万 - 项目类别:
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