When Tiffany House was growing up, she was often sick. But in that resilient way that children adapt to their bodies and their immediate world, she thought it was normal - normal for her.

Today, she weighs 90 pounds and, unable to walk, uses a wheelchair. She struggles with weak muscles and impaired lung function and is tied to weekly infusions of an experimental therapy. Yet the 18-year-old attends UTSA, deeply determined to lead a normal life - normal for her.

For Tiffany, enzyme replacement therapy is the only thing staving off further muscle deterioration and death. And right now, the future supply of the particular transgenic enzyme she is on - produced using genetically altered rabbits - is in question. Treatment issues will be high on the agenda at an international conference of scientists and patients originally set to begin Friday at the Holiday Inn River Walk, now postponed due to the Sept. 11 attacks. The meeting will be sponsored by the Acid Maltase Deficiency Association, founded in 1995 by Tiffany’s parents after she was diagnosed with the deficiency.

To read full article, please visit San Antonio Express-News

To response to Quest Article, please click here.

In order to keep up with the growing demand for the production of protein substances biopharmaceutical companies have several options:

• Build a new facility to produce new compounds, which would entail a cost of $200M-$400M and take three to five years to complete.

• Reserve “production slots” at a contract manufacturing facility such as Boehringer Ingelheim in Germany (The CHO enzyme for Pompe’s disease was produced at this facility).

• Or pursue transgenic drug production (carrying genes transferred from another species or breed)

The article focused on GTC Biotherapeutics in Framingham, Massachusetts (formerly Genzyme Transgenic Corporation), and emphasized that manufacturing of proteins in animals is the wave of the future. The article states:

• “it takes about 18 months to make a transgenic goat (8 months for a transgenic rabbit) that produces a desired therapeutic protein in its milk….in a cow….. (it takes) about 3 years…...”

• “....goats produce roughly 2 liters of milk a day, while cows produce about 20 liters a day.”

• “....creating a herd of transgenic goats costs about $100M….only a third the cost of building a protein production facility.”

• “The traditional method of production….which involves culturing large volumes of mammalian-derived cells and extracting their contents, costs about $150M a gram.” It is estimated that production of transgenic proteins will cost $1-2 a gram. (These costs contrast directly with what we have previously been told about transgenic enzyme production).

The future of transgenic therapy is also discussed in another article, which appeared in the San Antonio Express-News on September 11, 2002, entitled, “Cloning: Man Turns Creator” by Roy Bragg. Several biotech companies were mentioned including Infigen, Genzyme Transgenics, and Pharming (remember them). The article talks mainly about the production of transgenic cows which are so valuable that they are “kept under lock and key in a barn near De Forest, Wisconsin.” The article states.

“By splicing certain human genes into bovine embryo, the cloned offspring will produce specific human proteins in its milk. While a human might only produce a few grams of the protein, a cow could produce several hundred pounds of it in a year through twice-daily milking.”

“Genzyme Transgenics, a Framingham, Massachusetts based biotech company, has identified 60 proteins from the milk of genetically modified mice, rabbits, cows and goats that have pharmaceutical potential.”

This leads us to the search for a treatment for Pompe’s Disease. When scientists at Erasmus University Medical Center, Rotterdam, met a roadblock in their 25-year effort to develop a therapy for Pompe’s disease, they turned their approach to a new and novel way of producing the medicine - in animals rather than in the conventional reaction vessel. With the backing of an upstart Dutch pharmaceutical company, Pharming, a transgenic enzyme for Pompe’s disease was developed. Pharming entered into a joint venture with Genzyme Corporation, in October 1998, to develop and commercialize human alpha-glucosidase.

In July 2002, Genzyme Corporation abruptly halted production of the transgenic enzyme, although nine patients were still being treated with it. Catastrophes with improperly bottled enzyme and economic unfeasibility were cited by Genzyme as reasons for ceasing production. Genzyme wanted to focus on its new in-house produced CHO enzyme (Myozyme™) and the Novazyme product, which, at the time, was flaunted as being the second-generation treatment for Pompe’s disease. The Novazyme product has since disappeared from focus and what happened to the transgenic rabbit herd is anyone’s guess.

Of what interest is this to the patient who is anxiously awaiting treatment for Pompe’s disease? Perhaps it only gives us insight into the future of treatment for Pompe’s disease. The FDA under the Orphan Drug Act provides companies with incentives to develop a treatment for an orphan disease - a disease that affects a small number of people. The most notable incentive is the exclusive right to market the orphan product for seven years (ten years in Europe). If another production method is available at the end of this run, an additional seven years marketing exclusivity could be in the works.

What could this do? It would allow Genzyme to recover the initial investment cost of producing Myozyme™ while producing the next-generation drug at a reduced cost.

For example, in an article in May 2003 issue of Scientific American entitled, “The Orphan Drug Backlash”, the author Thomas Maeder states:

“A notable case of pricing and profit…(is) Genzyme’s Cerezyme. The drug, an enzyme replacement therapy for Gaucher disease, which afflicts 2,000 Americans, is the world’s most expensive medicine. Genzyme reportedly earns close to half a billion dollars a year from this treatment by charging patients between $100,000 and $400,00 a year for it, depending on whether the patient is a child or an adult. And the company did not lower the price when it switched from extracting the substance from human placentas to using the less expensive recombinant method of production. Patients, some of whom must spend their way into poverty to qualify for Medicaid to afford Cerezyme, are angry about the price but grateful for their lives.”

Will transgenic therapy be re-introduced as a treatment for Pompe’s disease? If so, will the introduction of a second, and possibly a third generation of enzyme therapy for Pompe’s disease, inhibit the development of gene therapy — “the cure.”Only time will tell.

When Randall and Marylyn House adopted their infant daughter Tiffany in 1983, they imagined her life would be without limits. “She was so beautiful and perfect,” Marylyn recalls. “We knew she was going to be President or a movie star.” But as their little girl grew, trouble emerged. Tiffany was slow to walk and climb stairs and struggled to fight off even a minor cold. By grade school, she was healthy enough to play tennis and join a swim team but remained clumsier and weaker than her peers. “I tripped a lot and couldn’t do a sit-up,” she says. “I thought I wasn’t good at sports. I didn’t think why.”

To read full article, please visit People Magazine

By doctor’s estimates, Tiffany House shouldn’t be alive today, more than 10 years after she was diagnosed with a rare, disabling genetic disease that robs its victims of muscle strength and, almost always, their lives.

But House, a petite, effervescent blonde who uses a wheelchair, is accustomed to being somewhat of a medical marvel.

On Friday afternoon, the 22-year-old was one of the elite few whose black cap and gown was accented by an orange and blue honor sash as she crossed the stage at the University of Texas at San Antonio, signaling her completion of a bachelor’s degree.

To read full article, please visit San Antonio Express-News

BUT…....this was after the $137 mil. Novazyme buy out, after John Crowley’s exodus from Genzyme, after the denigration of the transgenic therapy, after the abandonment of Novazyme’s NZ—1001——the “Holy Grail.”    Another eye opener came directly from Dr. Canfield, himself, at a forum of his peers. At this conference he was questioned and admitted that the “success” story of NZ-1001 was only produced once in his lab and never replicated——quite different from this Novazyme quote:

“It also clears massive amounts of glycogen from the muscle cells after just 6 hours. This is a finding that we have repeated several times…”

Was Genzyme “fooled?”  This is how a Genzyme Pompe Project Director phrased it when questioned at a conference. 

From what I deduce,  this story, “The Cure,” is just that—-a story!  It is a highly emotional depiction of a family distraught by the devastation of Pompe Disease.  However, the stories of all Pompe patients are emotional and devastating. Ultimately, it is controversial to some of us in the Pompe patient community because it does NOT depict a true picture!  It is an illusion. It is meant to sell books (maybe secure a movie deal), make money, and to portray John Crowley in a heroic fashion. 

John Crowley’s heroism is unfounded.  While he was successful in getting treatment for his children, his promises to others went unfulfilled. In effect, his children were given preferential treatment over other patients when they were “selected” for a sibling trial that was opened and closed before others even knew of its existence. 

We would be foolish if we did not learn from the past, for history has a way of repeating itself.  Crowley’s endeavors were rewarded once, and perhaps this current trend to honor Crowley is part of a grand scheme to recreate the illusion. 

This may be the ultimate plan (we will see), but in the meantime, let it be known that the AMDA does not endorse this book. 

Marylyn House

Before reading the book, I had anticipated an idolized view of John Crowley and his endeavors with Pompe Disease. However, after reading the book, what I perceived was a man that comes across as quite a “snake charmer”……OR is that a charming snake.

I think that all who read this book will be awe struck by the audacious nature of a man whose actions are based on snap judgments – not research and education. It’s chilling to think that this type of personality is perceived by many as a powerhouse figure—an innovator, a motivator, a leader.

John is true to this era—an era where the arrogant “elite” reign in dangerous positions. Their decisions, based only on their own mindset, can have disastrous results for the plebs “beneath” them. Yes, he is a good fit for the Enron Era—lies were told, things were made up, pockets were lined with $. All of this on the pretext of finding “The Cure.”

I remember the chaotic situations that arose during his tenure at Genzyme. There again, John made reckless and ill-informed decisions—decision that could have had disastrous repercussions for the entire Pompe project. Hopefully, this is a lesson learned, rather than one that is to be repeated!

I do commend Genzyme for finally taking the action to reel him in. However, I don’t think that Genzyme should have been so quick to “welcome” the publication of “The Cure.”Certainly, Genzyme’s business acumen, as documented in this book, leaves a lot to be desired!

“Genzyme Commends New Book for Portraying Challenges Faced by Patients with Pompe Disease and Their Families”—Genzyme press release August 31, 2006: http://genzyme.com/corp/investors/GENZ%20PR-083106.asp

My opinion,
Marylyn House
AMDA

Pompe disease, a rare, devastating and often fatal genetic disorder, is the subject of a major conference to be held Friday through Sunday at the Holiday Inn Riverwalk.

To read full article, please visit San Antonio Express-News

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Tiffany House was just 11 when she was diagnosed with a rare and often fatal disease called Acid Maltase Deficiency. Doctors told her she wouldn’t live into her 20s.

Now 26, House has been called a medical marvel, bucking her prognosis and leading a full life. She is president of the Acid Maltase Deficiency Association, created in 1995 by her parents, Randall and Marylyn House, to assist in funding research on her disease, often called Pompe disease, and to promote knowledge of Pompe. She is also a board member of the International Pompe Association and is the patient representative to the Food and Drug Administration, fighting to extend treatment possibilities to all patients.

To read full article, please visit UTSA Sombrilla

Elizabeth Nunnery takes her infant daughter, Zoe, to the hospital at 8:30 in the morning.  A nurse verifies Zoe’s medical information and hooks Zoe up to machines monitoring her blood oxygen level, heart rate, and respiration rate.  They take Zoe’s blood pressure and temperature.  A numbing cream is put on Zoe’s skin, above the port that she had surgically implanted in September.  A doctor cleans and sterilizes the port, a needle is inserted, and everything is taped into place.  Around 11 o’clock, the IV bag is placed on a pole and Zoe begins to receive her enzyme replacement.  Six and a half hours later, Zoe is unhooked and sent home.  They will repeat this process every two weeks for the rest of Zoe’s life. 

Dawn Kendall’s husband, Chuck, picks her up from the chair and helps her walk to the bathroom.  He helps her change into pajamas and he walks her to the couch.  He removes her socks and picks her feet up so that she can lie down.  He positions her so that she will not fall off the furniture.  Usually Kendall can crawl up the stairs to the bedroom, but today is a bad day.  Kendall cannot walk without assistance.  She has diminished lung capacity.  She gets headaches from straining the muscles in her shoulders and neck as she struggles to move.  She is still recovering from misdiagnosis and medication that caused additional health issues, including high blood pressure, low blood sugar, anemia, Vitamin D deficiency, hot flashes, cold sweat, and digestive problems.  She can no longer get out of chairs, lift her legs, or raise her arms straight over her head. 

Zoe Nunnery and Dawn Kendall have Pompe disease.  There is no cure.

To read full article, please click here.

In the wake of the recent article by Quest Magazine (January 2010) and the upcoming film “Extraordinary Measures” I feel that I must say something as to the accuracy of the story being presented to the world.

While some of the facts may be true, the story being told in the magazine and film are quite far from it. Yes, John Crowley’s children have Pompe. Yes, he formed Novazyme. And, yes, Genzyme bought Novazyme. However, that is about where the similarities end.

The truth is that the “product” create by Novazyme was never used in a single patient. The truth is that Myozyme is NOT a result of the collaboration between John Crowley and Dr. William Canfield at Novazyme.

The truth is that William Canfield admitted at a conference of his peers that the “super enzyme” he created wasn’t so super—in fact, the slides that he had shown people to prove how great it was at clearing glycogen were made using the wrong stain and he was never able to re-create the same results. (See the clip from the 2003 IPA Conference in Heidelberg, Germany).

At the end of the day, the credit for developing an enzyme replacement therapy goes to many people from all over the world. At the top of the list are the teams from Rotterdam, the Netherlands and Duke University who have devoted decades to research into Pompe and completed the first successful clinical trials with enzyme replacement therapy (albeit using different techniques).

Unfortunately, this is not the first time that the truth has been misplaced in the attempt to tell a good story. It happened when Quest published an article in March 2003, and when Geeta Anand wrote “The Cure.” For some reason, the hard work of many dedicated individuals gets left in the dust to tell a “story.” To me, that is a shame.

If you are interested in learning more of the TRUTH, please visit Dr. Kevin O’Donnell’s blog at: http://www.pompestory.blogspot.com. Kevin was a founding member of the International Pompe Association and was there to personally witness the triumphs and tragedies that have plagued our community.

For now, I would just like to caution everyone about believing everything they see in the movie. Remember that it is a Hollywood story. If you want to know the truth, seek it out for yourself. Don’t be fooled by Hollywood.

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As of January 20, 2010 there has been no response from the MDA concerning my comments of their article, despite emailing them directly.

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On Janurary 29, 2010 the AMDA received the following email from a woman who worked with Dr. Frank Martiniuk. Dr. Martiniuk was one of the first researchers the AMDA contacted, and he provided the AMDA with a great deal of information and advice.

Hi, I wanted to thank you for your post on “Pompe Disease: The Real Story”. I worked for and with Frank Martiniuk at NYU for 12 years and was a member of the team that published the first accurate DNA sequence for Acid Alpha Glucosidase.

Curiosity over the film led me to scan the book “The Cure” only to be quite distrubed by the description of Frank in this book where he was likened to the Scientist from “Back to the Future”, made it appear that he was non-responsive and not performing for Crowley. Although I don’t know everything about what really went on, but I know a lot and I know this was a reprehensible representation of a truly amazing man and offended me as if those words were directed at me (I was “Martiniuk’s assistant” who answered the phone in the book). I also know that Frank played a key role in helping put Genzyme on the right track, no biggie, that’s what scientists do. But he saved the company time, time that the Crowley’s didn’t have. I also know that Frank is the most brilliant and hard-working scientist I have had the honor to work with, and I’ve worked with some of the best. He could have been a world-reknown scientist, had he chosen a higher profile disease to dedicate his life to.

I’ve since earned my MBA and moved on, haven’t spoken with Frank for a couple of years, but was still with him when MDA failed to renew the grant that had funded his work on GAA, I had continued to follow his publications and my heart went out to him when I noticed he has been publishing on diseases such as leprosy. I just wanted to let you know that Pompe lost it’s most talented and dedicated scientist amongst all the celebration.

Thanks for letting me vent a little. I am very happy that your children have a treatment and wish them improved therapies tomorrow.

The AMDA has nominated Dr. Arnold Reuser and Dr. Ans van der Ploeg to the Rare Disease Day Research Hall of Fame. Drs. Reuser and van der Ploeg have spent decades researching Pompe disease, and from their research the first successful trials of enzyme replacement therapy for Pompe were started in January 1999 in Rotterdam, the Netherlands.

Please visit the Rare Disease Day Research Hall of Fame website to learn more about Drs. Reuser and van der Ploeg.

Additional information can also be found on Dr. Kevin O’Donnell’s blog: Pompe Disease—The Real Story