[Ellen Harris]

MTI-101 as potential new multiple myeloma treatment

by Ellen Harris on Fri Nov 09, 2018 3:51 pm

Hi all,

I hope this is a possible new path to a cure!

Emmons, MF, et al, "MTI-101 treatment inducing activation of Stim1 and TRPC1 expression is a determinant of response in multiple myeloma," Scientific Reports, June 2, 2017 (full text of article)

Abstract:

The emergence of drug resistance continues to be a major hurdle towards improving patient out­comes for the treatment of Multiple Myeloma. MTI-101 is a first-in-class peptido­mimetic that binds a CD44/ITGA4 contain­ing complex and triggers necrotic cell death in multiple myeloma cell lines. In this report, we show that acquisition of resistance to MTI-101 correlates with changes in expression of genes predicted to attenuate Ca2+ flux. Consistent with the acquired resistant geno­type, MTI-101 treatment induces a rapid and robust increase in intra­cellular Ca2+ levels in the parental cells; a finding that was attenuated in the acquired drug resistant cell line. Mechanistically, we show that pharma­cological inhibition of store operated channels or reduction in the expression of a component of the store operated Ca2+ channel, TRPC1 blocks MTI-101 induced cell death. Importantly, MTI-101 is more potent in specimens obtained from relapsed myeloma patients, suggesting that relapse may occur at a cost for increased sensitivity to Ca2+ overload mediated cell death. Finally, we demonstrate that MTI-101 is synergistic when combined with bortezomib, using both myeloma cell lines and primary myeloma patient specimens. Together, these data continue to support the develop­ment of this novel class of compounds for the treat­ment of relapsed myeloma.

Also:

Gebhard, AW, et al., "Mti-101 (cyclized HYD1) Binds to CD44 and Induces Necrotic Cell Death in Multiple Myeloma," Blood, ASH 2012 Abstract 4022 (full text of abstract)

[Mike F]

Re: MTI-101 as potential new multiple myeloma treatment

by Mike F on Tue Nov 13, 2018 11:57 am

Here's an article on one of the people involved in this research. It's pretty recent and sounds like they're getting ready to move into animal studies. Hope it works!

https://www.wvnews.com/news/wvnews/wvu-grad-student-researching-treatment-for-aggressive-blood-cancer/article_9045675f-28d9-5b8b-bd96-d6acef818dd4.html