18F-JSS20-183A for Tauopathies

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Pennsylvania

Disqualifiers: Pregnancy, Alcohol abuse, Substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

90 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the treatment 18F-JSS20-183A PET for tauopathies?

Research on similar PET tracers like [18F]PI-2620 and [18F]MK6240 shows they can help visualize tau protein build-up in the brain, which is linked to diseases like Alzheimer's and progressive supranuclear palsy. This suggests that 18F-JSS20-183A PET might also be effective in identifying tau-related brain changes in tauopathies. ^{1 2 3 4 5}

Is 18F-JSS20-183A safe for human use?

The study on 18F-PI-2620, a similar PET tracer for tau imaging, found it to be safe and well tolerated in both Alzheimer's patients and healthy individuals. ^{2 3 6 7 8}

What makes the drug 18F-JSS20-183A unique for treating tauopathies?

18F-JSS20-183A is a PET imaging agent specifically designed to visualize tau protein deposits in the brain, which are associated with tauopathies like Alzheimer's disease. This makes it unique compared to other treatments, as it helps in diagnosing and understanding the progression of these conditions rather than directly treating symptoms. ^{3 4 7 9 10}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for individuals with tauopathies like PSP, CBS, genetic FTLD, PD, AD or healthy controls. It aims to study a radiotracer's distribution and uptake in the brain. Participants will be recruited from multiple centers.

Inclusion Criteria

Investigators will ask disease cohort participants to agree to brain donation, but this choice is not mandatory for participation in this study

Clinical diagnoses will be determined by consensus committee for diagnostic agreement (PSP-RS, CBS, Genetic FLTD, PD only)

I am between 40 and 85 years old.

Exclusion Criteria

Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician or investigator to be a condition that could compromise participant safety or successful participation in the study

Contraindication to MRI, such as non-compatible implanted medical device

Females who are pregnant or breast feeding will be excluded, a urine pregnancy test will be performed in women of child-bearing potential prior to injection of 18F-JSS20-183A 11C-PiB or 18F-Florbetaben

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

PET Imaging

Participants undergo 18F-JSS20-183A PET scan to determine biodistribution, metabolism, excretion, and brain uptake

4 weeks

1-2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after PET imaging

4 weeks

Treatment Details

Interventions

• 18F-JSS20-183A PET

Trial Overview The study tests the biodistribution of 18F-JSS20-183A using PET scans, Brain MRI, Amyloid PET scans and neurological assessments to measure abnormal Tau protein deposits in various neurodegenerative diseases.

Participant Groups

Group I: 18F-JSS20-183A PET Experimental Treatment 4 Interventions

Participants will undergo 18F-JSS20-183A PET scan, they may also have a brain MRI and Amyloid PET scan as well as neurological assessments.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

The study demonstrates that the PET tracer [18F]AV1451 effectively visualizes tau pathology in a patient with frontotemporal dementia (FTD) associated with the V337M MAPT mutation, indicating its potential as a diagnostic tool for this condition.

There is a strong correlation between the degree of [18F]AV1451 binding and the extent of tau pathology and brain atrophy, suggesting that this imaging technique can provide valuable insights into the progression of tau-related neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontotemporal dementia with the V337M MAPT mutation: Tau-PET and pathology correlations. Spina, S., Schonhaut, DR., Boeve, BF., et al.[2022]

The PET imaging agent [18F]MK6240 effectively detects tau aggregates in the brain, showing a wide dynamic range of uptake in subjects with mild cognitive impairment (MCI) and Alzheimer's Disease (AD), which aligns with known patterns of tau deposition.

While various quantification methods for [18F]MK6240 were tested, including compartmental and reference tissue models, caution is advised in using simplified methods for high binding cases due to potential underestimation of tau levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects. Guehl, NJ., Wooten, DW., Yokell, DL., et al.[2023]

In a study involving 14 patients with progressive supranuclear palsy (PSP), 18F-AV-1451 PET imaging revealed distinct subcortical binding patterns indicative of tau pathology, particularly in areas like the putamen and globus pallidus, compared to healthy controls.

However, the study found no correlation between the levels of 18F-AV-1451 binding and the severity of motor dysfunction in PSP patients, suggesting that this imaging technique may not be ideal for assessing tau pathology in relation to clinical symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcortical 18 F-AV-1451 binding patterns in progressive supranuclear palsy. Cho, H., Choi, JY., Hwang, MS., et al.[2022]

The PET tracer 18F-PI-2620 effectively detects tau pathology in Alzheimer's disease patients, showing significantly higher binding in brain regions associated with tau deposition compared to healthy controls, indicating its potential as a diagnostic tool.

The administration of 18F-PI-2620 was found to be safe and well tolerated, with imaging results demonstrating a strong correlation between tau uptake and cognitive impairment, suggesting its utility in assessing disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study. Mueller, A., Bullich, S., Barret, O., et al.[2022]

The study found that the tau-binding radiotracer [18F]PI-2620 showed significantly higher uptake in the brains of Alzheimer's disease (AD) patients compared to cognitively normal individuals and those with mild cognitive impairment (MCI), indicating its potential as a diagnostic tool for differentiating AD from other cognitive states.

The analysis revealed specific brain regions, such as the occipital lobe and fusiform gyrus, where tau protein deposits were more pronounced in AD patients, aligning with known Braak Stages of tau pathology, which could help in identifying and understanding the progression of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Evaluation of Tau Deposition with [18F]PI-2620 by Using a Semiquantitative Method in Cognitively Normal Subjects and Patients with Mild Cognitive Impairment and Alzheimer's Disease. Jantarato, A., Vachatimanont, S., Boonkawin, N., et al.[2021]

The tau-PET tracer [18F]PI-2620 effectively differentiates between 3/4-repeat tauopathies (like Alzheimer's disease) and 4-repeat tauopathies (such as corticobasal syndrome and progressive supranuclear palsy) based on binding characteristics observed in PET scans of 39 patients.

Patients with 4R tauopathies showed higher delivery and efflux rates of the tracer, indicating less stable binding compared to those with 3/4R tauopathies, which could help in better understanding and diagnosing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binding characteristics of [18F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET. Song, M., Beyer, L., Kaiser, L., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Additive value of [18F]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Frontotemporal dementia with the V337M MAPT mutation: Tau-PET and pathology correlations. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Subcortical 18 F-AV-1451 binding patterns in progressive supranuclear palsy. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Rates of regional tau accumulation in ageing and across the Alzheimer's disease continuum: an AIBL 18F-MK6240 PET study. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

The Evaluation of Tau Deposition with [18F]PI-2620 by Using a Semiquantitative Method in Cognitively Normal Subjects and Patients with Mild Cognitive Impairment and Alzheimer's Disease. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Binding characteristics of [18F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Clinical Utility of 18 F-APN-1607 Tau PET Imaging in Patients with Progressive Supranuclear Palsy. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Tau PET imaging in neurodegenerative tauopathies-still a challenge. [2022]