A Diagnostic Test for Dementia with Lewy Bodies

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SUMMARY The objective of this study is to validate a diagnostic test for distinguishing two types of dementias—dementia with Lewy Bodies (DLB) and Alzheimer’s disease (AD). DLB is the second most common type of dementias after AD, affecting over 1.4 million people in the U.S. and is an aggressive neurodegenerative disease with no effective therapies. Progressive deposition of a misfolded phosphorylated protein, α-synuclein (P-SYN), within the central and peripheral nervous systems leads to neurodegeneration and is a pathological manifestation of this disease. Among 4 “synucleinopathies”—diseases characterized by the abnormal deposition of P-SYN in neurons—DLB is a dementia that is misdiagnosed in over 25% of patients because cognitive decline, one of its prominent clinical symptoms, is also a hallmark of a slower progressing AD. Diagnostic confusion between DLB and AD, particu- larly early in the disease, leads to 1) mistaken symptomatic patient care, which can accelerate cognitive decline, 2) invalid prognostic advice and 3) enrollment of incorrectly diagnosed patients in DLB and AD clinical trials, slowing down the development of treatments. Existing clinical consensus criteria, as well as imaging approaches, are insufficient to formulate precise diagnoses for dementias. These diagnostic challenges translate into an ur- gent unmet medical need for an accurate, reliable and accessible test to distinguish DLB from AD. CND Life Sciences is addressing this need through its core enabling technology, the Syn-One TestTM. This technology is based on a recent discovery that P-SYN deposition can be accurately measured in the skin of DLB patients with >97% sensitivity and specificity. Unlike detection of disease biomarkers, the Syn-One TestTM measures the ac- tual pathology within the autonomic nerve fibers of the skin based on the amount of P-SYN deposition and the extent of cutaneous nerve fiber degeneration. Importantly, the Syn-One TestTM is minimally invasive and is per- formed in 3 mm punch skin biopsies that can be obtained in any physician’s office without specialized equipment. CND Life Sciences’ feasibility studies demonstrated that P-SYN is detected in 100% of patients with confirmed DLB (n=21), and in none of the 18 AD patients, and that the densities of 3 distinct types of cutaneous nerve fibers are different between DLB and AD. In the proposed study, the precision of the Syn-One TestTM in distin- guishing DLB from AD will be optimized through measuring P-SYN deposition in patients with early DLB and AD diagnoses over a 2-year period (Aim 1), ensuring that pathological findings are confirmed by clinical disease diagnoses. Further, the metrics of neuronal degeneration will be defined by measuring the yearly rates of P-SYN deposition and cutaneous nerve fiber degeneration in DLB and AD patients (Aim 2). The results of this study will have an immediate impact on the clinician’s ability to develop appropriate care strategies for dementia patients. Defining the quantitative metrics of the relationship between cutaneous α-synuclein deposition and disease se- verity and progression will aid in the design of clinical trials and accelerate the development of effective therapies.