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The "Valley of Death" Looms for 8 Kids with a Rare Disease

Scientific American

The pharmaceutical industry rightly calls the stage in drug development between basic research and clinical trials the Valley of Death. This is when a potential treatment that s worked in mice, monkeys, and the like catapults to a phase 1 clinical trial to assess safety. It s rare.

Francis Collins, MD, PhD, director of the National Institutes of Health, calls this period where projects go to die. The reason: $.

Matthew Herper writes in that the cost of developing a new drug is $4-11 billion, not the $1 billion that Pharma often claims. Yet even that $1 billion is unimaginable, especially when you put a face on a rare disease and witness what the family goes through to leap to phase 1.

Ginger and Hannah. Photo: Dr. Wendy Josephs

For me, that face belongs to 8-year-old Hannah Sames, of Rexford, New York.

Hannah is one of only 54 people known in the world to have giant axonal neuropathy, or GAN. It s like ALS (Lou Gehrig s disease) in a child. Today Hannah needs a walker, but things are going to get worse, much worse unless, we all hope, she has gene therapy.

Her parents, Matt and Lori, are making it happen. Since Hannah s diagnosis in March 2008, they ve worked nearly around the clock to fund and assemble a team to use gene transfer to deliver the gene that Hannah needs directly into her spinal cord. Gene transfer becomes once it works.

Sometime within the next year, a neurosurgeon will delicately place several trillion adeno-associated viruses, each one harboring a working copy of the gene that is mutant in Hannah and seven others, into their spinal cords. If all goes well, the genes will stop the swelling and destruction of the nerves that s slowly robbing the children of their mobility. And since GAN has no treatments, other than those that ease day-to-day life, it s worth the gamble. There s no other option.

Through , the Sames family, and thousands of their neighbors in the capital district of New York, have raised a few million dollars, through events, tee-shirts, races, raffles, everything. They even won two Pepsi refresh grants of $250,000 each. Neighbors of the other GAN families have done the same. But it isn t enough. The Valley of Death looms.

Hannah s Hope has funded researchers at Emory University, Columbia University, the University of North Carolina and elsewhere to carry out the steps preceding the gene transfer experiment. And results have been so promising that the Food and Drug Administration (FDA) gave a tentative go-ahead this April, pending further toxicity studies in animals. Those are underway now, but cost $646,000 plunging Hannah s Hope Fund to the breaking point.

Lori estimates other costs:

- $430,200 for a 2-year for 12 patients to track the course of this ultra-rare disease, so that the researchers can determine exactly what to check to assess success. - $220,000 to manufacture the viruses and their human gene cargo - $600,000 for the phase 1, 2-year trial for 8 children - $450,000 for a small Phase 2 trial to assess efficacy

That s a total of $2,346,200. Then, hopefully, a biotech or pharmaceutical company will step in for the required larger phase 3 trials that precede FDA approval.

It sounds like a lot. But for comparison s sake, $2,346,200 equals:

- approximately 1/30th of Johnny Depp s fee for his next film - 1/10th of what Alex Rodriguez earns in a year - 10 speeches for Bill Clinton - 6 of Kate Middleton s wedding dress - 2 years worth of nanny-time for brood - Slightly more than Kim Kardashian s useless $2 million engagement ring - .07% of the money spent on the Obama and Romney as of March 2012.

The government isn t funding the GAN gene therapy trial. So what the tiny GAN community needs, desperately and now, is a Michael J. Fox, Christopher Reeve, or Julia Roberts.

Lori and Hannah Sames. Photo: Dr. Wendy Josephs

What the pharmaceutical industry and public health community need, for the long-term, is a new way of treating disease, such as gene or stem cell therapy. A one-time treatment that is effective would reduce or eliminate long-term supportive care, which is certainly in the interest of public health and reducing overall health care costs, says Steven Gray, Ph.D., the researcher at UNC who s engineering the viruses for the GAN trial.

Lori Sames explains it. Gene therapy is a disruptive technology to the pharmaceutical industry and is likely the solution for many ravaging disorders. We need help funding these proof-of-concept trials to help get gene therapy mainstream. We need help restructuring Pharma for these expensive, one-time treatments. What is the business model? How do you price it so payers will reimburse, yet be able to attract investors to develop the gene therapies?

I usually find new medical phrases awkward or unnecessary, like erectile dysfunction or histamine blocker, but disruptive technology is neither new nor meaningless. It perfectly describes gene therapy.

James Wilson, MD, PhD, professor of pathology and laboratory medicine at the University of Pennsylvania and a leader in the gene therapy community, in a recent editorial in , credited Harvard economist Clayton Christensen with originating the term in the mid 1990s.

A disruptive technology has no track record yet has the very real potential to have a huge impact, possibly pushing aside established approaches like iTunes. In contrast, a sustaining technology improves what s already available. And a gene therapy that works, as is the case for two types of hemophilia, for example, instantly renders obsolete costly protein replacement. In fact, a new journal from Mary Ann Liebert, Inc., debuts this month, providing a forum for reports on such innovative approaches.

Meanwhile, if funding materializes, Hannah and the other seven kids will have their gene therapy in early 2013, halting the inexorable jamming of their motor neurons. And the novel delivery to the spinal cord will pave the way for more common conditions, such as ALS, spinal muscular atrophy, and even spinal cord injuries.

This would be the first gene transfer trial that we are aware of to treat the whole spinal cord. And everything up until now has been funded by private donations, says Dr. Gray.

But all of the private donations aren t enough.

Please help Hannah, or any of the other 30 million people in the U.S. and those elsewhere suffering from .

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