Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Brain Tumor Cells Decimated by Mitochondrial "Smart Bomb"

25.03.2015

An experimental drug that attacks brain tumor tissue by crippling the cells' energy source called the mitochondria has passed early tests in animal models and human tissue cultures, say Houston Methodist scientists.

As reported on the cover of the April 2015 ChemMedChem (early online), Houston Methodist Kenneth R. Peak Brain & Pituitary Tumor Center Director David S. Baskin, M.D., and Peak Center Head of Research Martyn Sharpe, Ph.D. designed a drug called MP-MUS that destroyed 90 to 95 percent of malignant glioma cells, yet in other experiments did not seem to adversely affect healthy human brain cells (in vitro). This compliments a soon to be published extensive study showing the same drug can treat human brain cancer grown in the brains of mice. Researchers hope to begin testing the drug in human clinical trials in 2016 or 2017


Dr. David Baskin laboratory, Houston Methodist

The new drug MP-MUS (yellow) attacks cancer cell mitochondria by infiltrating both inner and outer membranes (green) after being converted from an inactive, non-toxic form to an active, toxic form by the enzyme MAO-B (purple). Once inside, the drug damages mitochondrial DNA, which cannot be repaired.

"We are very optimistic that we'll get there," said Baskin, also Vice Chair of the Department of Neurosurgery at Houston Methodist Hospital. "Our past work has shown that MP-MUS has very low toxicity until it gets into tumor cells. Once it arrives, it is changed to its active form, doing a lot of damage where we want it to, leaving healthy brain cells alone -- a bit like a 'smart bomb.' To our knowledge, this is the first known example of selective mitochondrial chemotherapy, which we believe represents a powerful new approach to brain cancer.”

Medical options for brain tumor patients are woeful, Baskin said. "It's a horrible diagnosis. Because of where the tumors are located, and because of the way they can infiltrate healthy tissue, surgery is often not helpful long term. The most effective chemotherapy drug available right now, temozolomide, only extends life from 9 to 15 months, and patients' quality of life during that period isn't very good."

For that reason, Baskin said, he and researchers around the world have been looking for new treatment approaches, such as vaccines intended to aid the body's immune system's recognition and removal of tumor cells, gene therapy and, in the present case, targeting tumor cell mitochondria.

Gliomas (a type of brain tumor) develop from brain cells called astrocytes. Gliomas account for as much as 20 to 30 percent of all tumors of the brain and central nervous system.

Mitochondria are often referred to as the "powerhouses" of cells -- including misbehaving cancer cells -- because they help cells create energy. In cancer cells this feature is partially switched off, causing cells to rely on other systems that generate energy. The numerous pill-shaped mitochondria in each cell perform a number of other crucial functions, however, and even cancer cells cannot grow and divide without healthy mitochondria.

As luck would have it, an enzyme called MAO-B is over-expressed in brain tumor cells, which is the target of MP-MUS. This means that healthy cells are only exposed to low levels of MP-MUS and their mitochondria to very low levels of P+-MUS, Baskin says.

On the other hand, in tumor cells the vast majority of the pro-drug is converted into P+-MUS, which essentially traps the drug inside their mitochondria where it attacks the mitochondrial DNA.

"We found that we could achieve profound effects with MP-MUS at very low concentrations, around 75 micromolar," said Baskin, Professor of Neurological Surgery, Weill Cornell Medical College. "By contrast, temozolomide must be used at concentrations two to three times that to be of any use to patients. Our approach is designed to capitalize on what is going inside the cells. Tumor cells have much more MAO-B, and when challenged, make even more MAO-B as a sort of defensive response. We hope that we are one step ahead of the cancer cells, as we are using that very fact to kill them."

The researchers reported MP-MUS's toxicity to healthy cells remained low at concentrations as high as 180 micromolar. This information will be useful to the researchers as they consider safety and efficacy trials in human patients.

Houston Methodist and Baskin and Sharpe entered into an agreement with Virtici, LLC to develop MP-MUS and are currently preparing toxicology studies which are required prior to clinical trials.

Also contributing to the ChemMedChem paper Junyan Han, Ph.D., and Alexandra Baskin, a student at St. Johns School. Funding the project were the Donna and Kenneth R. Peak Foundation, the Kenneth R. Peak Brain and Pituitary Center at Houston Methodist Hospital, the Taub Foundation, the Blanche Green Estate Fund of the Pauline Sterne Wolff Memorial Foundation, the Verelan Foundation, the Houston Methodist Hospital Foundation, the Dunn Foundation, and the American Brain Tumor Association.

ChemMedChem is a sister journal of Angewandte Chemie and is published by Wiley. The journal's impact factor was rated 3.0 in 2013 by the Institute for Scientific Information.

To speak with Dr. Baskin, please contact Gale Smith, Houston Methodist, at 832-667-5843 or gsmith@houstonmethodist.org.

While human clinical trials have not yet begun for MP-MUS, Houston Methodist Neurological Institute doctors are overseeing participation in a number of clinical trials related to gliomas and glioblastomas. The Kenneth R. Peak Brain and Pitutary Tumor Center provides highly personalized and specialized care for all patients with Brain tumors.

For more information, please visit http://www.houstonmethodist.org/clinicaltrials , and http://www.houstonmethodist.org/peakcenter

Contact Information
Gale Smith
Public Relations Manager
GSmith@houstonmethodist.org
Phone: 832-667-5843
Mobile: 281-627-0439

Gale Smith | newswise

Further reports about: BRAIN Cells Tumor brain cells brain tumor cancer cells concentrations mitochondria tumor cells

More articles from Life Sciences:

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

nachricht Snap, Digest, Respire
20.01.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Bodyguards in the gut have a chemical weapon

20.01.2017 | Life Sciences

SF State astronomer searches for signs of life on Wolf 1061 exoplanet

20.01.2017 | Physics and Astronomy

Treated carbon pulls radioactive elements from water

20.01.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>