Therapeutic treatment with OLX-07010 inhibited tau aggregation and ameliorated motor deficits in an aged mouse model of tauopathy

Targeting tau protein is a strategy for developing disease-modifying therapeutics for Alzheimer’s disease (AD) and numerous rare tauopathies. A small molecule approach targeting tau aggregation was used to select and optimize compounds that inhibit tau self-association in vitro, which have been translated into preventive studies in htau and P301L tau JNPL3 mouse models of tauopathy. In this treatment study, aged JNPL3 mice with pre-existing tau aggregates were used to evaluate the therapeutic effect of OLX-07010. The study had a Baseline group of mice aged seven months, a vehicle, and two dose groups treated until twelve months by administration in feed. The primary endpoint of the study was the reduction of insoluble tau aggregates with statistical significance. The secondary endpoints were dose-dependent reduction of insoluble tau aggregates, reduction of phosphorylated tau, reduction of soluble tau, and improvement of motor behavior. ELISAs and immunoblots were used to determine the ..., Animals
Female homozygous P301L tau JNPL3 mice (Lewis et al. 2000); Research Resource Identifier (RRID): IMSR_TAC:2508; Stock Tg(Prnp-MAPT*P301L)JNPL3Hlmc were purchased from Taconic Biosciences (Rensselaer, NY). The rationale for using females includes their more aggressive and less variable phenotype compared to male mice (Buccarello et al. 2017; Koppel et al. 2019), which can lead to more pronounced and measurable effects of the drug, making it particularly useful in early-stage studies to detect potential therapeutic benefits more clearly. Additionally, using female JNPL3 mice maintains consistency with previous research with OLX-07010 in the preventive study in JNPL3 mice, allowing for more direct comparisons and validation of results. A preventive treatment study with OLX-07010 in htau mice demonstrated its effectiveness in males, as well as its independence from sex (Davidowitz et al., 2023; Davidowitz et al., 2020). Ideally, highly powered studies including m..., , # Data from: Therapeutic treatment with OLX-07010 inhibited tau aggregation and ameliorated motor deficits in an aged mouse model of tauopathy

[https://doi.org/10.5061/dryad.1g1jwsv75](https://doi.org/10.5061/dryad.1g1jwsv75)

## Description of the data and file structure

The data was collected to evaluate the effect of therapeutic treatment using a small molecule OLX-07010 on an aged mouse model of tauopathy.

### Files and variables

#### File: Davidowitz_et_al._2025_Data_for_DRYAD_for_JNC_revised_07-22-2025.xlsx

**Description:** There were 4 Groups of mice in this study. A Baseline (BL) group, sacrificed at 7 months of age; A Vehicle (Veh) group and treatment groups dosed with 40 or 80 OLX-07010 mg/kg/day. Values for the paramaters are presented in columns in an Excel spreadsheet.

The in-life treatment and behavioral analyses were completed by end of 2020 and ELISA analyses were completed in 2021. 

**Figure 2**: Quantitative ELISAs for A. Sarkosyl insoluble tau, B. heat stable t...,