Although it is still considered an experimental technique, gene therapy shows promise for treating a wide variety of genetic diseases or disorders. In a recent news release from the Sanford Burnham Prebys Medical Discovery Institute, researchers discuss a gene therapy called AAV8-TNAP-D10. According to a preclinical study, a single dose of this gene therapy could be effective for patients with hypophosphatasia (HPP). Discover the full study findings published in the Journal of Bone and Mineral Research.

AAV8-TNAP-D10 Gene Therapy

Within this preclinical study, scientists sought to understand the safety and efficacy of AAV8-TNAP-D10. The treatment offers the opportunity to overcome the limitations of enzyme replacement therapy (ERT), such as frequent injections and injection site reactions. Normally, these asfotase alfa injections provide patients with the TNAP enzyme, which they are missing due to their HPP.

In this study, researchers evaluated one intramuscularly administered AAV8-TNAP-D10 injection in mice models of infantile HPP. Rather than administer TNAP via multiple injections, this gene therapy delivers a functional gene encoding for TNAP-D10. Ultimately, researchers determined that:

• Altogether, AAV8-TNAP-D10 prevented the formation of ectopic calcifications, or abnormal mineral deposits in tissues. Currently, this is a potential complication of the current standard-of-care.
• Additionally, this gene therapy improved overall survival and lifespan for the mice models.

Now, researchers hope this study highlights the need to undergo human trials in the future.

Hypophosphatasia (HPP)

Also known as soft bone disease, hypophosphatasia (HPP) is a rare genetic disorder and inborn error of metabolism. Caused by ALPL gene mutations, HPP is characterized by abnormal or defective mineralization in bones and teeth. Normally, mineralization occurs when phosphorus and calcium are placed into bones and teeth, strengthening them. With defective mineralization, the bones become soft. Additionally, the bones and teeth are more prone to fracturing or becoming deformed; patients are also at risk of losing their teeth prematurely.

There are multiple subtypes of HPP: adult, infantile, perinatal, childhood, prenatal benign, prenatal lethal, pseudohypophosphatasia, and odontohypophosphatasia. Signs and symptoms vary between patients. Additionally, some patients may present symptoms in infancy, while others do not appear until adulthood. Symptoms include:

• Anemia (low red blood cell count)
• Short or bowed legs
  • Note: Patients may also have other bowed limbs, particularly around long bones.
• Soft skull bones and large fontanelles in infants
• Decreased mobility
• Bone and joint pain
• Low muscle tone
• Frequent or recurrent fractures
• Hypercalcemia (high blood calcium levels)
• Emphysema
• Enlarged wrist and ankle joints
• Bone softening
• Narrow chest
• Teeth, rib, and finger abnormalities
• Seizures