big win

Rice and MD Anderson researchers discover exciting new leukemia treatment

Rice biochemist Natasha Kirienko and MD Anderson physician-scientist Marina Konopleva made the striking discovery. Photo by Jeff Fitlow

Rice University and MD Anderson researchers have just discovered a potential one-two punch that could, they hope, knock out an insidious disease.

A recent study in the journal Leukemia centers on potential new drugs that, with the help of other medications, can thwart leukemia cells.

Specifically, Rice biochemist Natasha Kirienko and MD Anderson physician-scientist Marina Konopleva screened some 45,000 small-molecule compounds to find a few that targeted mitochondria, according to Rice press materials.

In this innovative new study, the team selected eight of the most promising compounds, identified between five and 30 closely related analogs for each, and conducted tens of thousands of tests to systematically determine how toxic each analog was to leukemia cells. This was measured both when administered individually or in combination with existing chemotherapy drugs like doxorubicin, notes a release.

Previously, Kirienko’s lab had shown the eight compounds targeted energy-producing machinery inside cells called mitochondria. Mitochondria, which work nonstop in every living cell, wear out with use. The chosen eight compounds induce mitophagy, which can be described as how cells decommission and recycle deficient and used-up.

Notably, during times of extreme stress, cells can temporarily forgo mitophagy for an emergency energy boost. Previous research has shown leukemia cells have far more damaged mitochondria than healthy cells and are also more sensitive to mitochondrial damage than healthy cells.

Thus, Kirienko and Konopleva reasoned that mitophagy-inducing drugs might weaken leukemia cells and make them more susceptible to chemotherapy. Synergy — using two or more drugs in treatment — is key.

“The point of synergy is that there are concentrations, or dosages, where a single drug doesn't kill,” Kirienko said. “There is no death of healthy cells or cancer cells. But administering those same concentrations in combination can kill a considerable amount of cancer cells and still not affect healthy cells.”

The team tested the toxicity of its mitophagy-inducing compounds and combinations against acute myeloid leukemia (AML) cells, the most commonly diagnosed form of the disease. They then tested the six most effective AML-killing compounds against other forms of leukemia, finding that five were also effective at killing acute lymphoblastic leukemia (ALL) cells and chronic myelogenous leukemia (CML) cells.

Studies found all the mitophagy-inducing drugs caused far less harm to healthy cells.

Finally, the researchers tested one of the most effective mitochondria-targeting compounds, PS127E, using a cutting-edge technique called a patient-derived xenograft (PDX) model. Also referred to as a “mouse clinical trial,” mice are implanted with cancer cells from a leukemia patient. As the cells grow, the mouse is exposed to a drug or combination of drugs as a closer-than-cells test of the treatment’s effect.

Importantly, PDX tests on one compound, PS127E, showed it was effective at killing AML cells in mice, Rice notes, signaling promising news.

“Although this is very promising, we’re still some distance from having a new treatment we can use in the clinic,” Kirienko added. “We still have a lot to discover. For example, we need to better understand how the drugs work in cells. We need to refine the dose we think would be best, and perhaps most importantly, we need to test on a wide variety of AML cancers. AML has a lot of variations, and we need to know which patients are most likely to benefit from this treatment and which are not. Only after we’ve done that work, which may take a few years, would we be able to start testing in humans.”

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This article originally ran on CultureMap.

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Building Houston

 
 

The Ion has announced its latest startup-focused program. MediaTech Venture's Houston startup incubator is launching next month. Photo courtesy of the Ion

Houston has a new incoming incubator program for innovators within the media technology space.

The Ion announced a new partnership with MediaTech Ventures, an Austin-based global media industry venture development company, that will bring the MediaTech incubator program to Houston. Applications are open now, and the first cohort will kick off the program in January.

“Modern media has to continually evolve and adapt to new market channels, and with each platform comes the opportunity for innovation to leverage what is possible. It’s why Houston continues to build its market and resources for media technology entrepreneurs and startups looking to make an impact in this constantly evolving space,” says Jan E. Odegard, executive director of the Ion, in a news release.

“We’re thrilled to partner with MediaTech Ventures to further bolster the startups that are an integral part of our innovation community," he continues.

The 12-week program will help early-stage companies tackle marketing, development, and production with education and mentorship with MediaTech Ventures' startup curriculum and platform. The Ion will house the initiative and startups will have access to the hub for programming and networking.

“Ion is the perfect home for our incubator program,” says Josh Sutton, Houston Program Manager at MediaTech Ventures, in the release. “Our goal is to not only tap into the Ion’s valuable innovation ecosystem both within its four walls and beyond it, but to catalyze the development of media technologies and offer more resources for entrepreneurs looking to advance modern media.”

Founded in 2016 to advance the media technology economy, MediaTech Ventures focuses on "unifying innovation with capital, and validating and scaling technology-enabled media startups," per the news release. The program's startups have raised over $10 million following the completion of the curriculum.

An info session is taking place on December 5 at Second Draught in the Ion, and interested applicants can meet, ask questions, and learn more about the program.

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