Tag Archives: methioninase

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.

On The Case: Methionine & Cancer Part III

Before launching into more shocking truths about methionine, I want to share a story told by Chef Ryan Callahan in the August issue of Conquer magazine. Chef Ryan’s best friend, Tommy, was diagnosed with stage 4 liver cancer at 21 years old and died just 2 months later. Chef Ryan writes that Tommy had a 4th-degree black belt in Taekwondo and a healthy lifestyle overall. However, once Tommy began an aggressive course of chemo, he could only manage to eat salty junk foods and cookies.

Chef Ryan believes that if he’d understood and been able to teach Tommy’s family cooking techniques for countering chemo’s eating-related side effects, Tommy would not have died so soon.

Tommy’s story does make me curious about the role of Registered Dietitians during the course of his treatment – an RD should have assessed Tommy’s nutritional status and counseled him and his family about all the available options. But whatever the case may have been, this tragic story highlights the critical yet all-too-often ignored component of fighting cancer:

nountprriwtxicoin-use-use

truedat

Nowadays, patients and their families do have great resources. Chef Ryan was inspired to write a cookbook and offers tips and how-to videos. A reader also recently reminded me about Rebecca Katz,

rebecca-katz
Rebecca Katz wearing a zucchini noodle necklace

whose cancer-fighting food workshop I attended years ago as a dietetic grad student in Seattle. Rebecca has authored several cookbooks and released the Cancer Fighting Kitchen online course last month.

I’ve resolved to delve deeper into the material these two have developed as I continue to work on my cooking skills. Speaking of which, this weekend my fiance and I collaborated on making hamburger patties. We got a pound of grass-fed ground beef and mixed it with 1 pasture-raised egg, 2 cloves of minced garlic and a ½ teaspoon of turmeric along with salt & pepper.

burger
My fiance’s turmeric burger – I had mine sans bun alongside veggies

This was enough for three patties, and I had the leftovers for my Sunday lunch. We both enjoyed the beef but couldn’t really taste the turmeric, which was fine by my fiance. Still, the next time we make burgers, I might use a whole teaspoon of turmeric. If my fiance objects, I can up the seasoning on my portion only.

I’m leading this post with tales of my kitchen experiments in order to emphasize that the scientific literature on methionine restriction has not swayed me to cut out meat or otherwise alter my diet. As I’ve concluded in my previous post, far too much is still uncertain and the changes required would be maddeningly complicated at best – dangerous at worst.

Even if I could follow an ultra-low-methionine diet without jeopardizing my physical and mental health, the anticancer effect would not be assured. After all, researchers documented numerous cancer cell lines that were only slightly or not at all dependent on methionine. As far back as 16 years ago, an article in Cancer Research called for the development of a genetic test to identify methionine-dependent tumors in order to incorporate that information into efficacy studies for methionine-lowering treatments.

So where was this genetic test? Where were those efficacy clinical trials? Why did this promising research seemingly stall after Dr. Epner et al. published findings from a Phase I trial in 2002?

Google told me that Daniel Epner, M.D., was a Professor at The University of Texas MD bitmoji1174324671Anderson Cancer Center in Houston, TX. I reached out to Dr. Epner via email  to ask him why he left the field of methionine restriction research. To my surprise, he actually responded:

Marina,

I am sorry to learn about your cancer diagnosis. I wish you the very best in your treatment.

I led a basic science program for about 10 years at the beginning of my career during which I focused on abnormal nutrient metabolism as a potential target for cancer treatment. One of my main interests was methionine metabolism, since animal studies showed that dietary and or enzymatic methionine deprivation had anti-tumor activity. Methionine plays a key role in methylation of nucleic acids and proteins and is a key precursor for polyamines, both highly relevant to tumor growth.

We had support from Abbott laboratories for the phase I trial you mentioned in your email. In addition, Abbot supported a second clinical trial on which I collaborated with an investigator at MD Anderson (when I was still on the faculty at Baylor College of Medicine, before I moved to MD Anderson 8 years ago). That trial involved combining the experimental diet with chemotherapy for patients with primary brain tumors. However, my collaborator was unable to enroll a sufficient number of patients on that trial for reasons that were never clear to me. Perhaps his colleagues did not have faith in the strategy or perhaps patients were not enthusiastic about adhering to a strict dietary regime. Over time, Abbott became less enthusiastic about supporting the methionine restriction work since they did not think dietary methionine restriction would be commercially viable. 

Coincidentally at around that time, my career interests naturally evolved. I became very interested in psychosocial aspects of oncology, and I came to appreciate the power of relationships between doctors and their patients and families. This career evolution led to my interest and involvement in teaching communication skills and writing about relational aspects of oncology. Over time, my colleagues and I at MD Anderson decided I should transition to the department of Palliative Medicine, where I now reside, after having practiced medical oncology for about 20 years.  My main academic focus is now communication skills training and narrative medicine.   I still think methionine restriction is potentially viable as cancer treatment, but I have not actually worked in the field for many years. I know that Robert Hoffman PhD at Anticancer Inc. in San Diego has developed methioninase, the methionine degrading enzyme, as cancer treatment, but I do not know where that work stands now. You may want to contact him for an update and read his recent publications.

I still believe methionine deprivation is a very promising strategy from the purely scientific standpoint if you put aside marketing and other considerations. Nonetheless, I would strongly advise against anyone with cancer pursuing a methionine restricted diet outside of a clinical trial approved by an institutional IRB, just as I would advise against anyone receiving any form of experimental therapy outside of a clinical trial.

My thoughts and prayers are with you as you battle cancer.  I hope this information is helpful.

Best Regards,
Daniel E. Epner, MD, FACP

I appreciated his thoughtful reply. He confirmed my suspicion that funding was one of the barriers to moving forward with clinical trials, but also gave me a fuller picture of some of the other factors at play.

I do wonder why the follow-up clinical trial that Dr. Epner and his collaborator attempted had to focus specifically on brain cancer rather than, say, breast cancer or all metastatic cancers for that matter. But it’s usually not productive to ruminate about the past.ryanlerch-warning-cows-roadsign-2400px Besides, Dr. Epner had given me another lead to follow: Dr. Robert Hoffman. Searching for his work led me to AntiCancer, Incorporated. This company has a patent for and sells L-Methionine-g-lyase (METase), an enzyme that degrades methionine. genious-emoji

So there’s no need to follow a complicated diet, methioninase can do the job of breaking down methionine before tumor cells have a chance to feed on it, right? If that’s the case,  where are the clinical trials? Why aren’t researchers jumping on the chance to test this potentially life-saving treatment?

I emailed the company’s COO, Charlene Cooper, to find out if any human studies with methioninase were planned. I’ll share her reply, and more about methionine degrading enzymes as a treatment option for cancer, in my next post.
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