Tag Archives: research

How You Can Help Save 8 Million+ Lives per Year

I’m now officially a Living Beyond Breast Cancer (LBBC) Young Advocate!

LBBC Young Advocates Class of 2016

Shortly after getting back from Philly, I sat down to write a post about my experiences at the LBBC conference and plans going forward. But I began to feel that I was merely procrastinating – before anything else, I needed write the long-promised conclusion to my series on methionine.

Why do I keep stalling?

frustration

I’ve learned so much while reading about methionine research, but I don’t know how to act on that information except to report it.

Even after my advocacy training, I’m not sure what I can do besides lobbying for increased research funding. That’s important, but the whole legislative process is so so

Image by jesseakc

slow

 

 

 

 

In my last post on methionine, I found out about methioninase, an enzyme that causes methionine to degrade rapidly. Getting methioninase injections or taking methioninase pills would be far easier than trying to follow a methionine restricted diet.

For now, though, these pills & injections are the stuff of fantasy.methioninease-fairy-for-blog

I’d written to Charlene Cooper, COO of AntiCancer, Inc., the company that holds a patent for METase (a type of methioninase). I wanted to know when to expect human trials for this promising treatment.

Here’s Charlene’s reply:

Dear Marina,

Thank you for your email below.  We are very sorry about your diagnosis of metastatic breast cancer.

AntiCancer has developed recombinant methioninase through numerous pre-clinical studies, including primates and pilot clinical trials.  AntiCancer has had extensive discussions with the FDA and is ready to go forward with final toxicity studies and Phase I clinical trials.  The only hurdle is funding.

It is possible the “moonshot” initiative may be useful, but probabilities of funding from them are small.  I am attaching for you a paper (Development of recombinant methioninase to target the general cancer-specific metabolic defect of methionine dependence: a 40-year odyssey.  Expert Opin. Biol. Ther. 15, 21-31, 2015) from our President, Dr. Robert Hoffman, and another two other very important new papers on the use of methioninase in combination therapy.

We manufacture recombinant methioninase on site at AntiCancer Inc.  It is highly pure, but out facility does not have a good manufacturing practice (GMP) license as yet.

We would like to help you and also would appreciate your views for funding methioninase, one of the most promising developing cancer therapeutics.

Best regards,
Charlene

Charlene M. Cooper
Vice President & COO
Grants and Contracts Administrator
Executive Assistant to Dr. Robert M. Hoffman
AntiCancer Inc.

I appreciated the articles, and the time Charlene took to reply to me. But (sigh) how can funding still be a hurdle when we have the Cancer Moonshot Initiative and Mark Zuckerberg & Priscilla Chan pledging 3 billion to end/manage all disease? I have no views or particularly good ideas for funding methioninase trials. dunno-bitmojiThere’s MetAvivor.org,  but 40k per year is the max for their grants – I suspect that’s pocket change to businesses like AntiCancer Inc. Even if their human trials could get fully funded, it would probably take years and years to see results, not to mention FDA approval.

Before frustration could take over, I researched another company in the enzymes for oncology therapies business: Aeglea BioTherapeutics.

Founded less than three years ago, Aeglea develops engineered human enzymes invented in a lab a few miles away from me, at The University of Texas at Austin. One of the enzymes it’s working on is cystathionine-γ-lyase. It can degrade methionine like AntiCancer, Inc.’s methionine-γ-lyase enzyme, but the patent for cystathionine-γ-lyase claims that it would require less frequent injections for the same effect. More importantly, as a re-engineered version of an enzyme already found in humans, cystathionine-γ-lyase should not elicit an immune system response.

The lead author of the 2012 article on the development of cystathionine-γ-lyase, Everett Stone, still works at UT Austin, so I reached out to him. Professor Stone kindly agreed to meet with me to speak about the status of human methioninase research. It was Professor Stone who pointed me toward Aeglea – the cystathionine-γ-lyase ball is now in their court.ball-in-court-for-blog-rotated

Aeglea does list cystathionine-γ-lyase (product candidate AEB2109) on their product pipeline page, but it’s only one of seven and not even at the phase of Pre-Investigational New Drug (Pre-IND) Application with the FDA. This application is required before any Phase 1 human trials can take place.

Again, I have no good ideas about what I can do to speed this process along. Any suggestions, dear readers?

This whole investigation into methionine & methioninase has left me feeling like:

sharksurfingIt’s been ever so much fun, dodging this toothy shark – wonderful exercise, really! But once this boat towing me along runs out of gas, it would be great to have another one on standby to take me back to the beach.

Wooohooo, I see some boats in the distance, close enough to wave at. Hey boats, can one of you come give me a lift? Boats? Why are you crawling along so slowly? This is an especially toothy shark that I’m dealing with here, hellooooo…

Still, I refuse to give up hope for a cure, or at least more & better treatment options. Here then is my message in a bottle:

sea-bottle
Image by Comfreak

We all need to raise our voices to demand that  research on metastatic cancer be prioritized and well-funded. One easy way to do this is follow and support MET UP, whose legislative advocacy goals include:

  • Additional research funding for all cancer types. The National Institute of Health (NIH) currently funds ~ 8% of the grant applications it receives. That number needs to increase to 25% at the very least.
  • Allocating 30% or more of federal breast cancer research dollars to metastatic research – an appropriate goal considering that ~ 30% of those who survive earlier stages of breast cancer go on to develop metastatic disease.

Together, we could help build a boat big and fast enough, as it were, to save over half a million Americans who die from toothy shark – er, cancer each year.

On a global scale, cancer cures/effective treatments would prevent the death of > 8 million people per year! Since nearly 40% of people in the US will be diagnosed with cancer at some point in their lifetime, you might be helping yourself or your family just as much as you’d be helping me.

The Shocking Truth About Methionine: Part II

recap

In my last post, I discovered that many types of cancers have an absolute requirement for the essential amino acid methionine. When methionine is absent from petri dishes, malignant cells don’t grow and sometimes even die out completely. Normal cells in petri dishes can do ok without methionine provided they’re given homocysteine, methionine’s metabolic precursor.

That’s what happens in the lab. But how would it work in the real world? Methionine is in a lot of foods, especially animal foods. Yet becoming a Vegan wouldn’t be enough to eliminate dietary methionine –  it’s also abundant in seeds, nuts, soy, and beans. Besides, most every food has some amount of methionine, so a completely methionine-free diet isn’t feasible. And browsing through all those nutrition tables trying to approximate methionine content per typical portion was starting to drive me a bit crazy. aint nobody got time for that emoji

Still, if I could stick to an ultra-low methionine diet, would that help shrink my tumors? Is such a diet practical, or even safe? And would it be effective outside of petri dishes?

I turned to 720px-US-NLM-PubMed-Logo.svg .gov for answers. Studies testing the anticancer effects of methionine deprivation in mice looked promising. In one study, researchers injected 21 nude mice with Yoshida Sarcoma, a commonly used cancer cell line. One group of mice was fed 8.2g of methionine per kg, while the other group of mice got 0g of methionine per kg.

By day 12, all the mice with methionine in their diet were dead. In contrast, mice fed a methionine-free diet had slower tumor growth and even some regression of their tumors. At day 30, all the animals on the methionine-free diet were still alive, though the whole group died by day 38. Poor mice!

This literature is not the most fun to read. Still, survival time for one methionine-free mouse more than tripled, so they’ve gotta be onto something, right?

Researchers from the M.D. Anderson Cancer Center in Houston cast doubt upon these findings in a 1988 article; they reported that while three of the seven rodent tumor cell lines tested failed to grow in a petri dish without methionine, all 17 of the human tumor cell lines tested were able to grow in the methionine-free petri dishes. I'm over it emojiThe researchers concluded that methionine dependence is less likely to occur in human tumors than rodent tumors.

Just as I was about to dismiss the whole idea of methionine restriction, I found a study that was novel in its use of human (as opposed to rodent) breast, colon and lung tumors. Growth of these human tumors (transplanted as usual into nude mice) was significantly inhibited in the mice fed a methionine-free diet. This demonstrated that at least some types of human cancers require methionine in living (albeit all-too-briefly-living) animals. Maybe this did warrant further exploration.

Fast forward to 2016: scientists still seem stuck on using nude mice to investigate the role of methionine in cancer progression. One such study published this year focused specifically on breast cancer. Mice were injected with immortalized human breast cells and fed either a control diet consisting of 0.086% methionine or a methionine restricted diet with only 0.012% methionine. After 12 weeks, all the mice were euthanized (when will these poor little creatures catch a break?) and examined. Tumors weights in the methionine restricted mice averaged 11.4±4.0 mg compared to a 20.2±6.1 mg tumor weight average in the control mice. That’s a 55% tumor weight reduction for the methionine restricted diet vs. a standard control diet.

I’d be super excited by these results…sticker.crazyhamsterif I were a rodent injected with malignant cells (but not marked for euthanization).

More than 40 years have passed since the initial discovery at the University of California. Where were the human clinical trials? Ridic emojiI did finally dig up a small Phase I clinical trial from among all the mouse and petri dish experiments. This trial had modest objectives and only eight patients with various types of metastatic cancer.  Participants followed a methionine restricted diet for an average of approximately three months, and their plasma methionine levels fell by an average of 58%. The authors concluded that a methionine restricted diet can be safe and tolerable in adults with advanced cancer.

Not much more than that can be learned from a trial with so few participants, but I still felt underwhelmed by the results (or lack thereof). Certainly no miraculous recoveries for any of those eight patients. One patient with prostate cancer had a 25% reduction in serum prostate-specific antigen (PSA) after three months on the diet, and another patient with renal cell cancer experienced “an objective radiographic response.”

Otherwise, the trial didn’t find any notable anticancer effects from methionine restriction, not even in the patient who followed the diet for 38 weeks. Maybe a 58% drop in plasma methionine isn’t enough to cause the tumors to regress? In any case, I doubt I’d manage to be much more strict with my methionine intake than these eight trial participants.

The researchers called for more clinical trials to determine whether methionine restriction could enhance the anticancer activity of chemo and other treatments. Why couldn’t I find any of those follow-up trials?

what Happened emoji

I decided to contact one of the authors, Dr. Epner, to ask him directly why he abandoned this line of research after publishing the Phase I trial results in 2002. I’ll save Dr. Epner’s response and further adventures in methionine research for my next installment.

As for my progress in cooking turmeric dishes, I’ve been sticking with the tried and truly delicious turmeric potato salad.  I made and devoured it three more times since my last post. Maybe I’ll feel more venturesome and try a new recipe this week. Stay tuned!

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