José Luis Millán, Ph.D. and his lab have studied hypophosphatasia, an inherited disease that makes bones dangerously fragile, for the past 15 years. The researchers developed a mouse model of the disease—mice that, like their human counterparts, lack an enzyme called alkaline phosphatase. Then, just about five years ago, scientists from Enobia Pharma approached Millán. They had developed an enzyme replacement therapy called ENB-0040 and they needed someone who could help them test it—someone with a model and with extensive knowledge of hypophosphatasia and the alkaline phosphatase enzyme. So Millán and his team administered it to their mice. Mice with hypophosphatasia usually survive for 20 days at most. When the treated mice were alive at day 21, Dr. Millán knew they were onto something promising.
Buoyed by these results, researchers led by Hal Landy, M.D. at Enobia and Michael P. Whyte, M.D. at Shriner’s Hospital for Children in St. Louis (the world’s clinical expert on hypophosphatasia) began testing ENB-0040 in young patients with infantile hypophosphatasia—the most severe form of the disease, in which babies are born with almost no alkaline phosphatase activity. Now, a paper published March 8 in the New England Journal of Medicine reveals the results of this clinical trial. Ten patients were treated with ENB-0040 for six months while researchers tracked their development and lung function, and evaluated the drug’s safety.
What they found was striking. In just six months, nine of the 10 patients were dramatically improving—they showed improved developmental milestones and lung function. With longer treatment, bones healed. All without any serious side effects.
While we can’t yet call ENB-0040 a cure for hypophosphatasia, for some of the study’s participants, it’s been life-changing. Three year-old Corinna couldn’t walk when she began taking ENB-0040. Just eight weeks later, she wasn’t just mobile—she was running and jumping. (Click here to read more about Corinna and watch a video of her exciting recovery.)
Enobia Pharma—recently acquired by Alexion Pharmaceuticals—hopes to obtain FDA approval for ENB-0040 as a treatment for infantile hypophosphatasia in the next couple of years. In the meantime, they will begin testing ENB-0040 in adults with less severe forms of hypophosphatasia.
“I feel privileged to have been able to play a part in developing this treatment for hypophosphatasia, and to see that what we’ve been learning at the lab bench for more than 15 years has actually been translated to the clinic and is saving children’s lives,” said Millán, professor in the Sanford Children’s Health Research Center at Sanford-Burnham.
Whyte MP, Greenberg CR, Salman NJ, Bober MB, McAlister WH, Wenkert D, Van Sickle BJ, Simmons JH, Edgar TS, Bauer ML, Hamdan MA, Bishop N, Lutz RE, McGinn M, Craig S, Moore JN, Taylor JW, Cleveland RH, Cranley WR, Lim R, Thacher TD, Mayhew JE, Downs M, Millán JL, Skrinar AM, Crine P, & Landy H (2012). Enzyme-replacement therapy in life-threatening hypophosphatasia. The New England journal of medicine, 366 (10), 904-13 PMID: 22397652