TPI 287

TPI 287 is a medication being developed by Cortice BioSciences for the treatment of Alzheimer’s disease, progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS).

How TPI 287 works

Alzheimer’s disease is a tauopathy, a class of diseases caused by the misfolding of a protein called tau in the brain. Twisted tangles of tau protein, as well as clusters of protein fragments called beta-amyloid, are hallmarks of Alzheimer’s.

Tau normally forms part of a structure in the cell called microtubules, which play important roles in nutrient transport within the cell. In Alzheimer’s disease, the misfolding of tau causes the microtubules to collapse and ultimately leads to cell death.

TPI 287 is able to reach the brain and stabilizes microtubules inside nerve cells. It is hoped that the medicine can stop, or even reverse, the course of Alzheimer’s disease.

The treatment of mice models of tauopathy with TPI 287 and other microtubule stabilizing agents that penetrate the brain have been shown to improve cognitive performance and/or nerve cell activity.

TPI 287 in clinical trials

A Phase 1 clinical trial (NCT01966666) assessing the safety, tolerability, pharmacokinetics (movement of the medicine in the body), pharmacodynamics (how the body processes it), and effectiveness of TPI-287 in Alzheimer’s disease patients is ongoing.

Results from the study were announced during the Clinical Trials on Alzheimer’s Disease (CTAD) 2017 meeting. At the time of final analysis, 29 patients with mild-to-moderate Alzheimer’s disease had been randomized in the trial, with 20 receiving TPI 287 and nine receiving placebo.

The primary goal of the trial was safety. There were two episodes of non-serious hypersensitivity reactions observed in patients treated with TPI 287 versus none in the placebo group. One additional patient who was treated with TPI 287 experienced a grade 3 anaphylactoid reaction, (a reaction characterized by hives, swelling of the larynx, or shock) which was categorized as a serious adverse event.

Cognitive assessment was done using the mini-mental state exam (MMSE) before and 12 weeks after the start of treatment in 26 patients, 18 treated with TPI 287 and eight with placebo. MMSE consists of a few questions that are designed to reveal particular memory issues. Lower MMSE scores are associated with greater disease severity.

After 12 weeks from the beginning of the treatment, the change in MMSE scores in the patients treated with TPI 287 ranged from -2.4 to 2.4 (no change), and the change in patients treated with placebo ranged from -4.6 to -1.4 (a worsening). The difference between the two groups was statistically significant.

Other information

TPI 287 is supported by the non-profit organization PSPCure, which focuses on neurodegenerative diseases that strike when people are in their 50s to 70s, including Alzheimer’s disease.

Cortice Biosciences is a clinical-stage drug development company pioneering novel therapies for the treatment of oncologic and neurologic disease indications with urgent unmet medical need.

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