Hypophosphatasia (HPP), or "soft bone disease" is a rare genetic disorder that impacts bone and tooth development, leading to weak bones and other health complications. For years, enzyme replacement therapy has been the only effective treatment for HPP. This therapy involves injecting asfotase alfa, an enzyme that replaces the missing one in patients’ bodies. However, these injections must be given three to six times a week, which can be challenging for many patients. While the treatment has saved many lives, it remains invasive and temporary. Additionally, side effects such as injection site reactions, redistribution of body fat, calcium buildup in the eyes or kidneys, and the development of antibodies that may reduce the drug's effectiveness are common. For some patients, the side effects may outweigh the potential benefits.
HPP can cause problems like premature tooth loss and bone fractures. The severity of HPP varies; mild cases make adults more likely to break bones, while severe cases in infants can be life-threatening. Now, researchers are exploring gene therapy as a potential one-time solution. A single injection of this therapy could provide a lifelong supply of the missing enzyme.
A recent study by Dr. José Luis Millán and his team tested a new gene therapy, called AAV8-TNAP-D10, on mice. This therapy uses a harmless virus to deliver the gene responsible for producing the missing enzyme. Results have shown that AAV8-TNAP-D10 therapy successfully delivered the TNAP gene to the liver, prompting the production of the enzyme that is deficient in HPP. This enzyme was then secreted into the bloodstream, where it was able to reach bones and teeth, which in turn successfully improved bone mineralization, reduced fractures, and alleviated dental issues in the mice. Notably, the study tracked the mice for a period of 12 months, demonstrating that the effects of the treatment were long-lasting, with the therapeutic enzyme continuing to circulate in the bloodstream and reach bones and teeth for an extended duration.
Interestingly, the research revealed a difference in how male and female mice responded to the therapy, with female mice needing smaller doses for effective results. While this difference is known to occur in mice, scientists believe it is unlikely to affect humans. Still, they will keep an eye on this during future clinical trials.
With promising results from these studies, the next step is to prepare for human clinical trials. The researchers are also working to address potential long-term complications of HPP that current therapies don’t fix, such as issues in the brain, liver, or kidneys. This gene therapy could be a game-changer, improving patients' quality of life and reducing the burden of frequent treatments and side effects.
Created: Feb 4th, 2025
Citations:
ScienceDaily. (2025, February 3). Gene therapy restores enzyme levels to treat hypophosphatasia. https://www.sciencedaily.com/releases/2025/02/250203163834.htm
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