Fixing Bad Bones: A "Shot" at a new life

Painful steps, weak bones and shorter limbs are just a few of the problems patients with a certain bone disorder face every day. Until now there was nothing doctors could do to fix it. Luckily, there's a new treatment that's giving young patients hope for a better life.

Purses, shoes and blouses, for Karlee Wurster this is normal. But early on, the 16-year-old knew something about her was very different.

"I had an aide that walked around with me," said Karlee Wurster who was diagnosed with a genetic disorder.

At six months old, Karlee was diagnosed with a genetic and sometimes deadly disorder called, "Hypophosphatasia. My bones are undermineralized, so it means they're just weaker than everyone else's," says Wurster.

For some infants the diagnosis can be a death sentence. For others, it brings frequent bone breaks. For Karlee it meant a life of pain.

"Was frequently started using a wheelchair," describes Katherine L Madson PhD, MD, a Pediatric Rheumatologist at the Center for Metabolic Bone Disease and Molecular Research.

That was until four years ago when researchers began testing a drug called ENB-0040 that replaced her missing enzyme, which is needed for bone growth and calcification.

Once injected, the drug goes straight to the bone. Similar to insulin injections, patients inject themselves sometimes daily. Within weeks some infants grew new bones, some reached other milestones.

"They'd come in and show us how far they could jump or look at how fast I can walk," says Dr. Madson.

While others assessed their success with steps, Karlee counted something else.

Karlee Wurster
"Shopping, I mean I used to only go like 20 minutes,” says Wurster.

"She can do at least 2 hours," says Kimberly Wurster Karlee’s Mother.

After six weeks the pain was all but gone, and so was her wheelchair.

"We're shoe shopping a lot,” says Wurster.

It's a pain free shopping spree and Karlee's breaking the bank, not her bones.

Doctor Madson says side effects of the drug she hears about from patients include stinging and bruising near the injection site.

Researchers don't yet know if patients will have to continue injections for the rest of their lives. The drug is in phase two clinical trials and is not yet FDA approved.

MEDICAL BREAKTHROUGHS
RESEARCH SUMMARY

TOPIC: Fixing Bad Bones: A "Shot" at a new life
REPORT: MB # 3499

BACKGROUND: Hypophosphatasia is an inherited, rare bone disease whose clinical symptoms are highly variable, ranging from a profound lack of mineralization of bone with death occurring prior to delivery up to early loss of teeth in adulthood as the only sign. Still other affected individuals may have the characteristic biochemical abnormality but no outward clinical signs of the disorder. Hypophosphatasia is due to consistently low levels of an important enzyme in the body, alkaline phosphatase. (SOURCES: Healthline, Gale Encyclopedia of Public Health)

THE PROBLEM: Alkaline phosphatase (ALP) is present in nearly all plants and animals. There are at least four different genes known to encode different forms of ALP in humans. Hypophosphatasia is due to a deficiency of the form of ALP that is particularly abundant in the liver, bones, and kidneys. This is often referred to as the tissue non-specific form of ALP, or TNSALP. This form of alkaline phosphatase is important in the mineralization, or hardening, of the bones of the skeleton as well as the teeth. Thus, abnormalities in either the production or function of this enzyme have a direct effect on the formation and strength of these parts of the body. In general, the more severe forms of hypophosphatasia are associated with lower serum TNSALP activity for that individual's age. (SOURCES: Healthline, Gale Encyclopedia of Public Health)

TREATMENT: Doctors at Washington University School of Medicine in St. Louis, working with Shriners Hospital for Children and other institutions, have identified a promising new treatment. The experimental treatment used in the study, ENB-0040, is a manufactured form of normal alkaline phosphatase, but enhanced so that it is targeted to bone.

After six months of treatment, most patients showed substantial healing of rickets. After one year, six patients were breathing unaided. Of the nine patients who completed one year of treatment, all made progress, sometimes significant, in motor development. One progressed to moving all limbs against gravity, one to sitting unsupported, two could crawl, one pulled to standing, and two started taking steps. Of the two older children who could only sit, both progressed to walking after a year of treatment.

Treating these patients by giving them normal alkaline phosphatase is not a new idea. More than two decades ago, Michael P. Whyte, MD, professor of medicine, of pediatrics and of genetics at Washington University School of Medicine in St. Louis and his colleagues attempted to treat patients with hypophosphatasia by giving them blood plasma with excess alkaline phosphatase. That unsuccessful study showed that raising alkaline phosphatase levels in the blood was not enough. More recently, Whyte's industry collaborators have provided the missing link: Adding a short protein chain that adheres to bone allowed the alkaline phosphatase to be targeted to the skeleton.

Paving the way for this human study, Whyte and his colleagues then showed that the targeting chain worked well in a mouse model of severe hypophosphatasia, restoring normal life span to mice, as long as they received daily injections of ENB-0040 starting at birth. The nine patients who completed one year of treatment continue to receive therapy and are now participating in an extension study. For more information about clinical trials recruiting patients with hypophosphatasia, visit clinicaltrials.gov./ (SOURCE: Washington University)Bottom of Form

FOR MORE INFORMATION, PLEASE CONTACT:

Amy Reeves, MS, CCRP
314-432-3600 x 1022
areeves@shrinenet.org


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