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 ?7-nicotinic acetylcholine receptor (?7nAChR), which amyloid beta 1-42 (A?42) 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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44AG057329-03
Application #
9850182
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Luo, Yuan
Project Start
2018-09-30
Project End
2020-06-30
Budget Start
2020-02-01
Budget End
2020-06-30
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Cassava Sciences, Inc
Department
Type
DUNS #
134270623
City
Austin
State
TX
Country
United States
Zip Code
78731