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Tolfenamic Acid Is Associated with Decreases in Mutant Huntingtin and Oxidative Stress

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a drug class that reduce pain, decrease fever, prevent blood clots and, in higher doses, decrease inflammation. One such drug, Tolfenamic Acid, which is presently used in the UK and other countries for the treatment of migraine headaches, recently was shown to have neuroprotective properties, and to alleviate learning and memory deficits in the APP transgenic mouse model of Alzheimer’s disease.

However, it remained to be seen if Tolfenamic Acid could prevent motor and memory dysfunction in transgenic animal models of Huntington’s disease (HD), until now.

A team of Chinese researchers recently conducted a clinical trial using mice to evaluate motor and memory function. The results of the trial were quite promising, especially since it's a drug that is already on the market.

According to the study paper, the researchers concluded: Collectively, the results of the present study suggest that tolfenamic acid can attenuate motor and cognitive deficits in R6/1 transgenic mice. Tolfenamic acid could promote the degradation of mHtt by inhibiting the transcription factor Sp1 and enhancing autophagic function. Antioxidant production in the brains of R6/1 mice and in PC12 cells is another important mechanism of tolfenamic acid. It has been established that tolfenamic acid is safe for clinical use. Therefore, our data support tolfenamic acid as a potential candidate for the treatment of HD.

To read the paper in its entirety please click here.


1 Comment

Herwig Walter Lange
Herwig Walter Lange
Apr 15, 2019

Let's hope that these findings are reproducible. Data mining in enroll-HD is a good idea to see, if there are HD patients treated with tolfenamic acid and if they are better off than other HD patients. One problem might be dosage: HD-mice were given 25 or 50 mg/kg body weight. Hummans take 200 mg once or twice a day, that is max. 400 mg / 80 kg = 5 mg/kg. Tolfenamic acid has a relatively low acute toxicity with LD50 values in 200-1000 mg/kg. So, 50 mg/kg should be safe in humans. By the European Medicine Agency, it was granted in 2016 with the status of orphan for the treatment of supranuclear palsy ( At the time of submi…

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