Bradley F. Boeve, M.D.

The purpose of this study is to evaluate sporadic (s-) and familial (f-) frontotemporal lobar degeneration (FTLD) patients and asymptomatic family members of f-FTLD patients, characterizing the cohorts longitudinally and informing clinical trial design.  FTLD is a neurodegenerative disorder of the nervous system which there are no approved treatments or cures.

The study has two arms: a “longitudinal arm” involving a comprehensive assessment of clinical, functional, imaging, and biofluid data collection, and a “biofluid-focused arm” involving limited clinical data to accompany biospecimen collection.

The purpose of this study is twofold:

Specific Aim 1

• In biopsies of skin from living subjects with DLB, PD without dementia (PD), and PD with dementia (PDD), assess the relative diagnostic sensitivity and specificity of IHC and seeding assay measures of aSyn, relative to normal control subjects.

Specific Aim 2

• In second biopsies of skin from subjects with DLB, PD and PDD, assess whether IHC and seeding measures of aSyn progress, regress or remain stable over time, indicating whether these may be useful as measures of therapeutic agent target engagement and disease progression.

To further investigate biomarkers in CSF as possible predictors for mild cognitive impairment and dementia

Longitudinal Imaging Biomarkers of Disease Progression in Prodromal and Overt DLB

Most individuals with rapid eye movement (REM) sleep behavior disorder (RBD) develop additional
neurological symptoms and are subsequently diagnosed with overt synucleinopathies, including dementia with
Lewy bodies (DLB), Parkinson disease (PD), and multiple system atrophy (MSA), indicating that RBD
represents a prodromal stage of synucleinopathy. RBD therefore offers a window of opportunity to intervene
with neuroprotective treatments at the earliest stages of disease when treatment is most likely to be effective.
Recognizing the importance of early intervention, key federal agencies focused on neurodegenerative disease
have proposed high priority recommendations for prodromal aspects of synucleinopathies, including
specifically RBD, to prepare for clinical trials. The North American Prodromal Synucleinopathy (NAPS)
Consortium began in 2018 to plan for neuroprotective clinical trials in RBD. The NAPS Consortium, currently at
10 sites, has thus far enrolled 215 participants with polysomnogram-confirmed RBD, and has successfully
performed comprehensive and standardized assessments and biofluids collection. The North American
Prodromal Synculeinopathy Consortium for RBD, Stage 2 (NAPS2) program represents an integrated
expansion of NAPS to support a longitudinal, prospective study of RBD, to address key gaps currently
prohibiting neuroprotective clinical trials in RBD. NAPS2 will establish enhanced infrastructure to support longterm
research in prodromal synucleinopathies.

The purpose of this study is to evaluate the safety, tolerability and drug/body interactions of C2N-8E12 in patients with progressive supranuclear palsy.

The purpose of this study is to evaluate the effect of neflamapimod on cognitive function as assessed in a study-specific Cogstate Neuropsychological Test Battery (NTB).

The purpose of this study is to evaluate the safety and effectiveness of Nelotanserin for the treatment of visual hallucinations in patients with Lewy body dementia.

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AL001 in participants with a  frontotemporal dementia.

The primary objective of this study is to assess the safety and tolerability of TPN-101 in patients with C9ORF72 amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD).

The purpose of this study is to demonstrate the effectiveness of neflamapimod, compared to placebo, as a treatment for DLB, as assessed by the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB).

This study seeks to evaluate the efficacy and safety of intepirdine (RVT-101) in patients with dementia with Lewy bodies.

The primary purpose of this study is to evaluate the efficacy of AL001 compared with placebo in carriers of progranulin gene (GRN) mutations causative of frontotemporal dementia (FTD) as measured by the Clinical Dementia Rating Dementia Staging Instrument PLUS National Alzheimer’s Disease Coordinating Center frontotemporal lobar degeneration Behavior & Language Domains Sum of Boxes (CDR® plus NACC FTLD-SB).

The purposes of this study are to investigate the safety, tolerability, and pharmacodynamics of FRM-0334 in subjects with prodromal to moderate frontotemporal dementia with granulin mutation.

The purpose of this study is to assess the safety and tolerability of CT1812 as a treatment for mild-to-moderate Dementia with Lewy Bodies.

The objectives of the study are to; (1) estimate the change in disease -related cognitive decline over 1 year on a battery of cognitive tests administered to participants with early-stage symptomatic Behavioral Variant Frontotemporal Dementia (bvFTD) phenotypic variant; (2) identify the cognitive test or brief battery of cognitive tests which are the most sensitive to detect bvFTD progression; (3) determine the optimal schedule of administration of cognitive tests to detect bvFTD progression; (4) evaluate the relationship between cognitive tests and measures of behavior, function, caregiver's burden, quality of life (QOL); and (5) obtain blood samples for genetic and exploratory biomarkers correlations.

The purpose of this study is to examine the effects of the medication Armodafinil in patients who have dementia with Lewy bodies which is associated with memory loss and other thinking problems, excessive daytime sleepiness, hallucinations, delusions, apathy, and reduced quality of life.

This study seeks to evaluate the long-term safety and effectiveness of nelotanserin for the treatment of visual hallucinations (VHs) and Rapid Eye Movement (REM) Sleep Behavior Disorder (RBD) in subjects with Lewy body dementia (LBD).

To further investigate biomarkers in CSF as possible predictors for mild cognitive impairment and dementia

The investigators propose using DaTscan in patients with mild cognitive impairment (MCI), Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease (AD), and other neurodegenerative syndromes and disorders, to test several hypotheses - some confirmatory, and some novel. Such use will provide new data on the potential clinical and research utility of DaTscan in neurodegenerative diseases. The findings on DaTscan will be correlated with clinical diagnoses and other multimodal imaging studies (e.g., MRI, MRS, FDG-PET, and amyloid-PET) to enhance our understanding of neurodegenerative diseases.

This study is being done to identify and characterize neurophysiological biomarkers for progression of neurodegenerative disease from physiological and subjective measurements.

This study is being done to learn more about normal thinking and behavior, mild thinking and behavior problems, Frontotemporal Dementia and other forms of dementia in families in which one or more relatives have a mutation associated with Frontotemporal Dementia.

The objective of the study is to use myocardial 123I-MIBG scintigraphy along with other clinical, neuropsychological, and neuroimaging findings to identify which patients with the following syndromes/diagnoses/features who have probable underlying Lewy Body Disease:

• dementia;
• parkinsonism;
• mild cognitive impairment;
• REM sleep behavior disorder;
• REM sleep without atonia, as well as in those with normal neurologic functioning.

This is an open-label study using a radioligand and SPECT scan. The safety results will be presented using descriptive statistics. Qualitative assessments of the extent and intensity of the heart to mediastinum (H/M) ratio, and quantitative assessments (median and distributions of H/M ratio) for the various syndromes and disorders will be compared to normal controls, and between the various syndromes/disorders.

The purpose of this study is to establish a registry of RBD patients, develop quantitative biological and functional measures of synucleinopathy burden, and establish a formal process to evaluate candidate neuroprotective agents.

The purpose of this study is to collect and analyze blood specimens from individuals carrying known familial frontotemporal lobar degeneration (f-FTLD) mutations compared to a control group of individuals without known f-FTLD mutations.