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Title : Ibudilast for a cocktail?
link : Ibudilast for a cocktail?

Ibudilast for a cocktail?

Ibudilast was approved in Japan in May 1989.
In 2016, the drug was approved by the US FDA.
In 2017, the drug was approved in the EU.

https://www.ncbi.nlm.nih.gov/pubmed/30814573
https://www.nature.com/articles/s41598-019-39427-4

In vivo, combined ibudilast and TMZ treatment of a patient derived xenograft (PDX) model resulted in significantly longer overall survival. Our findings have significant clinical implications for people with GBM. Since clinical trials involving ibudilast have shown no adverse side effects and the drug readily penetrates the blood brain barrier, treatment of GBM with this combination is clinically achievable.

MIF inhibition in combination with ibudilast and TMZ treatment results in longer survival in vivo. Tumor-bearing mice were treated with indicated drug combinations with the following doses: Ibudilast (5 mg/kg); Ibudilast (20 mg/kg); TMZ (10 mg/kg); Ibudilast (5 mg/kg) + TMZ (10 mg/kg) and Ibudilast (20 mg/kg) + TMZ (10 mg/kg). There were n = 8 mice in all groups. All treatments ceased by day 100.

At 43 days post-implantation, large tumors were present and treatment commenced. When all vehicle-treated mice reached their neurological endpoint (median survival 100.5 days), treatment was stopped. The treatment of tumor-bearing mice with ibudilast only resulted in inferior median survival times compared to the vehicle-treated mice (89 days and 97.5 days respectively) (Fig. 5A). A survival advantage was observed with mice treated with TMZ alone (median survival: 105.5 days compared to 100.5 days; LogRank p = 0.055). Combined treatment resulted in significantly longer survival. Mice treated concurrently with ibudilast (5 mg/kg) and TMZ (10 mg/kg) displayed a median survival of 114 days (p = 0.005) while the combination of ibudilast (20 mg/kg) and TMZ (10 mg/kg) resulted in a median survival of 111.5 days (p = 0.014).

P.S. The authors of the study write about a significant improvement in the survival of mice, but we see that the best survival in the treatment with a combination of drugs is 114 days versus 105.5 days in the treatment with temozolomide alone.

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