Dendreon, a biotechnology company, has reported promising preclinical data demonstrating the potential of D-3263, the company’s orally bioavailable small molecule, which targets TRPM8, to treat benign prostatic hyperplasia.
D-3263 has demonstrated the ability to reduce benign prostatic hyperplasia (BPH) alone and in combination with finasteride, a current treatment for BPH.
In a preclinical study, BPH was induced in rats through subcutaneous injection of testosterone propionate (TP). Approximately one week after initiation of BPH, either D-3263, finasteride or a combination of the two agents was administered daily for two weeks. Following treatment, blood was sampled, prostates were collected and weighed, and tissue sections were examined histologically.
According to Dendreon, rats with TP-induced BPH who were treated with D-3263, finasteride or a combination of the two, had a significant reduction (p=0.004) of mean prostate weight and prostate hyperplasia with evidence of a dose response. In addition, the highest dose of D-3263 given in combination with finasteride resulted in lower prostate weights than either agent given alone, suggesting a potential additive effect.
BPH-induced animals showed increases in dihydrotestosterone (DHT) concentrations in the plasma, levels of which were reduced in animals treated with D-3263, finasteride or a combination of the two. While finasteride is a known inhibitor of 5-alpha reductase, the enzyme that converts testosterone to DHT, D-3263 is not an inhibitor of this enzyme suggesting that the two agents may act by different means to affect androgen metabolism and prostate hyperplasia, the company said.
David Urdal, chief scientific officer of Dendreon, said: BPH is a condition that affects a significant number of men, and based on the preclinical data announced today demonstrating the drug’s ability to reduce the size and weight of the prostate, we believe that D-3263 may be able to impact this disease.
We are also exploring the role of TRPM8 in cancer, given that TRPM8 is upregulated on cancer cells. A Phase I clinical trial to evaluate this molecule against multiple types of solid tumors has been recently initiated.