Rare diseases and drug discovery don't usually make for Hollywood blockbusters. But today (January 22) a film about a genetic affliction that strikes fewer than 10,000 people worldwide hits movie screens, and it has some serious star power behind it. Harrison Ford and Brendan Fraser head up the cast of Extraordinary Measures, a new movie that may lift Pompe disease from the shadows of obscurity into the spotlight, as the focal point of an inspirational story of paternal love and scientific innov
By Jef Akst | January 22, 2010
Rare diseases and drug discovery don't usually make for Hollywood blockbusters. But today (January 22) a film about a genetic affliction that strikes fewer than 10,000 people worldwide hits movie screens, and it has some serious star power behind it. Harrison Ford and Brendan Fraser head up the cast of Extraordinary Measures, a new movie that may lift Pompe disease from the shadows of obscurity into the spotlight, as the focal point of an inspirational story of paternal love and scientific innovation.
A screen shot from the movie. Note The Scientist's poking cameo appearance next to the computer(black arrow). Image: YouTube trailer (screen shot)
"The movie is a great exposure for a rare genetic disease," said Duke University School of Medicine's linkurl:Priya Kishnani,;http://www.dukehealth.org/physicians/priya_kishnani who studies Pompe and participated in much of the research that led to the first and only approved treatment for the disease -- a quest that forms the central plot of the film. "I would have never thought in my lifetime, a disease that I'm so passionate about would make it into mainstream Hollywood cinema."
Extraordinary Measures tells the tale of businessman linkurl:John Crowley;http://www.crowleyfamily5.com/ (played by Fraser) who makes it his mission to promote the development of an enzyme therapy to treat his two youngest children, who are sick with Pompe. Teaming up with University of Nebraska researcher Robert Stonehill (Ford), Crowley starts a small biotech company called Priozyme dedicated to his purpose. (In reality, the researcher who helped Crowley was William Canfield of the University of the Oklahoma Health Sciences Center, and the company Crowley launched was called Novazyme.)
Pompe disease is a genetic lysosomal storage disorder. Any of the nearly 300 mutations in the lysosomal enzyme acid α-glucosidase (GAA) gene that affect its function can result in either infantile- or late-onset accumulation of glycogen in muscle tissues. Pompe destroys skeletal muscle, impairing motor skills and usually relegating patients to wheelchairs. The disease also compromises lung and heart function, with most Pompe patients ending up on ventilators with inflamed and failing hearts. Infants with Pompe disease typically survive less than one year, while late onset patients can suffer only mild symptoms for years before experiencing an abrupt decline.
As the movie depicts, Novazyme was eventually bought out by linkurl:Genzyme;http://www.genzyme.com/ (Zymagen in the movie), a larger biotech company that was also developing a Pompe therapy and had purchased two others. Now with four different enzymes to choose from, Genzyme ran what they call the "Mother of All Experiments," pitting the four candidates against one another in blinded biochemical analyses and mouse model tests to see which held the most promise. Once the results were in, a group that included Canfield, as well as Genzyme's vice president, Robert Mattaliano, selected the winner, revealing the drug's identity by decoding the color-schemed key.
There was "this great collage of [people with] the desire to come up with something would serve the needs of this patient population," Mattaliano told The Scientist. "It was quite a team effort."
The winner -- a recombinant human form of the GAA enzyme (rhGAA) produced in a Chinese hamster ovary cell line -- was the subject of three clinical trials: one for infantile-onset Pompe patients, one for patients aged 3 months to 3.5 years, and one for the two Crowley children, who were able to receive treatment at a local New Jersey hospital near their home after their father left his position at Genzyme.
The trials showed significantly decreased mortality, and patients were able to survive longer without the aid of a ventilator, and some even demonstrated increased motor function. In 2006, the treatment, an intravenous enzyme replacement therapy dubbed Myozyme, became the first and only approved treatment for Pompe disease. While Crowley's children are still on respirators, they are responding well to their Myozyme treatments, which they continue to this day.
Extraordinary Measures tells this story with remarkable accuracy (albeit with some minor Hollywood name changes and plot tweaks), and shines a light on Pompe that rarely touches most rare diseases. But somewhere in the recounting of this emotionally driven tale, the viewer, at least the scientifically-inclined one, is alienated from the realities of the disease. The sick children, while on ventilators and in wheelchairs, speak with ease -- an overly optimistic picture of Pompe patients, who often have much more difficulty communicating. The movie also typecasts theoretical endeavors as idealistic and even useless, dismissing a branch of research that provides the basis of most bench and clinical work.
The film does a better job of representing the hard-to-swallow fiscal issues of drug development. "The movie emphasizes how these things can be monetized," University of Florida pediatric cardiologist linkurl:Barry Byrne;http://www.mgm.ufl.edu/faculty/bbyrne.htm told The Scientist. "Everything cannot be done at the research level," added Byrne, who was involved in the clinical trials of Myozyme. "Without investments from a company like Genzyme to bring these products to patients there would be no benefit to patients in the long run."
Since the development of Myozyme, research on treatments for Pompe disease has continued and expanded. Most recently, Byrne opened a linkurl:clinical trial;http://clinicaltrials.gov/ct2/show/NCT00976352?term=pompe&rank=4 to test a gene therapy supplement to the enzyme replacement therapy. A handful of biotechs are also developing new Pompe drugs, including Genzyme which is currently working on their second generation compound.
"It's really striking that for such a small community of patients that there is so much interest," Byrne said. "And [hopefully it will be] catalyzed by the public interest in the film."
**__Related stories:__***linkurl:A lab goes to Hollywood;http://www.the-scientist.com/article/display/23150/ [March 2006]*linkurl:The Scientist Video Awards: 2009;http://www.the-scientist.com/videoawards [August 2009]*linkurl:Communicating through movies;http://www.the-scientist.com/article/display/15240/ [14th February 2005]
I'm looking forward to this movie! \n\nI just watched "Living Proof", a perhaps similar movie in that it depicts the difficulties a researcher went though to get the necessary by-in from a biotech company in order to develop and take through clinical trials the drug Herceptin (for breast cancer). In this case, even with lots of privately raised funding, the researcher really had to struggle with the biotech company's board to keep the clinical trials going. Difficult movie to watch, but brilliant acting and story.
Kudos to the Scientist for reviewing this film and highlighting the heartbreaks and triumphs associated with researching rare diseases. It is incredibly inspiring to follow the progress of organizations tirelessly pursuing treatments for rare diseases. Lymphangioleiomyomatosis is a rare, fatal disease affecting only women, mainly in their childbearing years. Two remarkable organizations have been formed to raise money to fund research on this rare disease, one by a patient (http://lamtreatmentalliance.org/index.html) and the other by the mother of a patient (http://www.thelamfoundation.org/). Thank you for reviewing this film, and focusing attention on rare diseases.
I haven't yet had the opportunity to see this movie, but from what I've heard I am a little concerned about it's accuracy.\n\nDoes it mention the enormous contributions to the development of Pompe reatments made by the research groups lead by Arnold Reuser and Ans van der Ploeg at Erasmus University in Rotterdam and Professor Yuan-Tsong Chen at Duke University? \n\nhttp://pompestory.blogspot.com/2009/05/turning-of-tide.html \n\nhttp://www.dukehealth.org/health_library/news/duke_research_leads_to_extraordinary_measures_film\n
While this movie does recount the story of John Crowley's quest for a cure for Pompe disease and the contribution of Canfield's (Stonehill in the movie) work, they do not go into detail on the three other therapy candidates that were tested in the blind "Mother of All Experiments" tests. There is mention of the other groups that are also working on developing Pompe treatments (specifically, Crowley argues that these groups should be working together instead of in competition), but no further details are provided.
It does seem a little unfair to exclude the scientists at Rotterdam and Duke whose work predated and underpinned both Genzyme and Novazyme drugs. \n\nBoth the Rotterdam and Duke groups developed, through the biotechs Pharming and Synpac, treatments that were successful in clinical trails. These clinical trials were already under way when Novazyme (Crowley and Cranfield's company) announced their first exciting in vitro results. Ultimately Genzyme's Myozyme, developed a little later, won the race to FDA approval. \n\nThe Novazyme candidate failed in animal studies and did not enter clinical trails.\n\nI respect the work John Crowley did a to raise awareness of Pompe disease and to help persuade a pharmaceutical company to devote time and money to developing and producing a threament for a fairly obscure genetic disease. I also recognize that not every promising candidate makes it to FDA approval, after all Pharming and Synpac's candidates were pulled before gaining FDA approval despite very promising clinical trial results because Myozyme looked a little better in the "Mother of all experiments" and could be produced more easily. \n\nNonetheless the fact that a major Hollywood production about the discovery and development of a treatment for Pompe fails to give due credit to the scientists who did the hard work is symptomatic of the problems faced by science in the media today.\n\nAnd I haven't even got on to the role of the mice and quail;-)\n\nhttp://speakingofresearch.com/2010/01/25/pompe-disease-%E2%80%93-a-starring-role-for-animal-research/
\n\n**Nonetheless the fact that a major Hollywood production about the discovery and development of a treatment for Pompe fails to give due credit to the scientists who did the hard work is symptomatic of the problems faced by science in the media today**\n\n\nI COMPLETELY AGREE
\n\n\nHello Paul,\n\nIs it unusual that the media (scientific press, social media) fail to give due credit to scientists pioneering discoveries to humankind benefit?\n\nNo. And perhaps one of the major reasons is just lack of complete information, which is something ?fixable?. Perhaps, and for the sake of public education, it is about time to start correcting the problem, in an unusual way. \n\nWhat about providing an ADDENDUM to the movie ? Extraordinary Measures? apologizing for unintentionally omitting the instrumental pioneering contributions, to the development of Pompe treatments, by Arnold Reuser and Ans van der Ploeg at Erasmus University in Rotterdam and Professor Yuan-Tsong Chen at Duke University?\n\nUnprecedented? I don?t know but easily doable. I guess that Harrison Ford, an actor who I admired very much, could do it in his computer with a simple 2-slides PowerPoint and e-mailing it to the major movie distributors. \n\nHarrison, if you need help, I can help you with that!\n\nThank you.\n
That's an interesting idea Rafaela, I'll suggest it to a couple of people who are far more closely involved in Pompe disease research and advocacy than I am. \n\nIt's far too late to do anything about the movie theater, but an addition to the DVD or official website might still be possible.\n
In the wake of a handful of biosafety lapses at federal research facilities, the US government is temporarily halting funding for new studies aiming to give novel functions to influenza, SARS, and MERS viruses.