Tauopathies

This is a phase II study intended to evaluate the safety, tolerability and pharmacodynamics of NIO752 in participants with primary tauopathies. Eligible participants will be randomized to receive either NIO752 or placebo during the double-blind treatment period followed by an Open-label Extension (OLE).

In the field of diagnosing brain neurodegenerative diseases, it is now a well-established practice to inject positron-emitting tracers into the human body. These tracers bind to specific target proteins, allowing their distribution to be visualized via PET imaging. Currently, several research groups worldwide are engaged in developing and clinically validating their own tau imaging agents. This clinical research project aims to visualize abnormal tau pathology in the living human brain using \[18F\]NIDF PET imaging. \[18F\]NIDF is a 2-arene-azaindole-based tracer that offers stronger binding affinity to tau neurofibrillary tangles and reduced non-specific/off-target binding compared to existing tau-PET imaging agents. The study primarily focuses on evaluating the safety and diagnostic efficacy of \[18F\]NIDF PET imaging in human subjects.

To evaluate the potential usefulness of 18F-S16/T807 positron emission tomography/computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in various Tau-related disease patients.

MARKERS-NDD is a prospective, observational, longitudinal study, which aims to collect data from patients affected by neurodegenerative diseases (NDD) followed longitudinally for routine examinations performed as part of normal clinical practice. Data collected from clinical evaluations, movement analysis, brain imaging, neuropsychological and electroencephalographic assessments, blood chemistry tests will be analysed to carry out statistical investigations and predictive analyses, also using artificial intelligence systems, which allow the identification of new early markers of diagnosis and prognosis of neurodegenerative diseases.

The current protocol is to determine the biodistribution, metabolism, excretion and brain uptake of 11C-M503. The goal of this radiotracer is to quantify alpha-synuclein that is abnormally deposited in the brain of people with Parkinson's disease (PD). Investigators will compare uptake in participants with PD versus participants with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), as well as non-Parkinsonism volunteers. This multicenter project funded by an NIH U19 grant, is centered at U Pennsylvania (Penn, Grant PI: Robert Mach) in collaboration with U Pittsburgh (Pitt) (non-clinical site) Yale U, U of California at San Francisco (UCSF) and Washington University in St. Louis (WU). The University of Pennsylvania will act as the sIRB for this multi-center human subjects project and participants will be recruited from all sites.

This current protocol will provide the key data to help determine the specificity of our to-be-developed radiotracers by implementing a multi-site diagnostic assessment core and PET imaging of A-beta amyloid (may be completed at some sites as part of another protocol) that is commonly deposited in the brains of people with Parkinson's Disease (PD), Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP) or Frontotemporal Dementia (FTD) as well as healthy controls. This multicenter U19 grant is centered at U Pennsylvania (U Penn) (PI: Robert Mach) in collaboration with U Pittsburgh (Pitt), Yale University, U of California at San Francisco (UCSF) and Washington University in St. Louis (WU). U Penn will act as the single IRB of Record (sIRB) for this multi-center project and subjects will be recruited from all sites.

The current protocol is to determine the biodistribution, metabolism, excretion and brain uptake of 18F-JSS20-183A. The goal of this radiotracer is to quantify 4Repeat Tau (4Rtau) protein that is abnormally deposited in the brain of people with a class of neurodegenerative diseases called tauopathies, such as Progressive Supranuclear Palsy (PSP), Corticobasal Syndrome (CBS), syndromes of genetic Frontotemporal Lobar Degeneration (genetic FTLD) as well as participants with Parkinson disease (PD), Alzheimer's Disease (AD) and healthy controls. This multicenter project funded by an NIH U19 grant, is centered at U Pennsylvania (Penn, Grant PI: Robert Mach) in collaboration with U Pittsburgh (Pitt), Yale U, U of California at San Francisco (UCSF) and Washington University in St. Louis (WUSTL). The University of Pennsylvania will act as the sIRB for this multi-center human subjects project and participants will be recruited from all sites.

The current protocol is to determine the biodistribution, metabolism, excretion and brain uptake of 11C HY-2-15. The goal of this radiotracer is to quantify alpha-synuclein that is abnormally deposited in the brain of people with Multiple System Atrophy (MSA). The investigators will compare uptake in people with MSA with people with Parkinson disease (PD) and progressive supranuclear palsy (PSP) as well as healthy volunteers. This multicenter project funded by an NIH U19 grant, is centered at U Pennsylvania (Penn, Grant PI: Robert Mach) in collaboration with U Pittsburgh (Pitt) (not a clinical site), Yale U, U of California at San Francisco (UCSF) and Washington University in St. Louis (WU). The University of Pennsylvania will act as the sIRB for this multi-center human subjects project and participants will be recruited from all sites.