[Multibilly]

Amiloride - a diuretic to treat multiple myeloma?

by Multibilly on Sat Aug 12, 2017 9:11 am

Just came across this article.

Rojas, E., et al, "Amiloride, an old diuretic drug, is a potential therapeutic agent for multiple myeloma,"Clinical Cancer Research, Aug 2017 (abstract)

It's only been tested in mouse models thus far, so I'm trying not to get too excited about it. But wouldn't it be great if you could use a simple diuretic that costs about $5/month to help control myeloma?

Abstract:

Purpose: The search for new drugs that control the continuous relapses of multiple myeloma is still required. Here, we report for the first time the potent anti-myeloma activity of amiloride, an old potassium-sparing diuretic approved for the treatment of hypertension and edema due to heart failure.

Experimental Design: Myeloma cell lines and primary samples were used to evaluate cytotoxicity of amiloride. In vivo studies were carried out in a xenograft mouse model. The mechanisms of action were investigated using RNA-Seq, qRT-PCR, immunoblotting and immunofluorescence assays.

Results: Amiloride-induced apoptosis was observed in a broad panel of multiple myeloma cell lines and in a xenograft mouse model. Moreover, amiloride also had a synergistic effect when combined with dexamethasone, melphalan, lenalidomide and pomalidomide. RNA-Seq experiments showed that amiloride not only significantly altered the level of transcript isoforms and alternative splicing events, but also deregulated the spliceosomal machinery. Additionally, disruption of the splicing machinery in immunofluorescence studies was associated with the inhibition of myeloma cell viability after amiloride exposure. Although amiloride was able to induce apoptosis in myeloma cells lacking p53 expression, activation of p53 signaling was observed in wild-type and mutated TP53 cells after amiloride exposure. On the other hand, we did not find a significant systemic toxicity in mice treated with amiloride.

Conclusions: Overall, our results demonstrate the anti-myeloma activity of amiloride and provide a mechanistic rationale for its use as an alternative treatment option for relapsed multiple myeloma patients, especially those with 17p deletion or TP53 mutations that are resistant to current therapies.

[Janet1520]

Re: Amiloride - a diuretic to treat multiple myeloma?

by Janet1520 on Sun Aug 13, 2017 4:37 pm

Wow! This sounds hopeful, especially for those of us with 17p deletion.

[wenlock00]

Re: Amiloride - a diuretic to treat multiple myeloma?

by wenlock00 on Wed Oct 18, 2017 11:00 am

Good to see that you are trying the amiloride and I hope you will be able to restart it soon. If it is an existing drug being used off label, then I am surprised they are not getting into a trial.

[Multibilly]

Re: Amiloride - a diuretic to treat multiple myeloma?

by Multibilly on Thu Oct 19, 2017 2:26 pm

Setting up a clinical trial takes a tremendous amount of work and costs a great deal of money. I used to ask this question all the time about various potential treatments until I had a better understanding of just what it takes to do a trial.