UCLA researchers PEGylated NELL-1 by random conjugation using 3 different PEG sizes. The thermal stability, cytotoxicity, in vivo bioactivity, and pharmacokinetic behavior of the multiple forms of PEGylated NELL-1 were evaluated and the most effective forms were selected. Specific forms of PEGylation of NELL-1 significantly increase the elimination half-life of the protein from 5.5h to 15.5h while distributing more than 2-3 times the amount of protein to bone tissue in vivo. Systemic NELL-PEG therapy administered every 4-7 days significantly increases not only percent bone volume but also new bone formation throughout the overall skeleton after 4 weeks of treatment.
Abstract
UCLA researchers have developed ways to chemically modify NELL-1, an osteoinductive factor, that significantly prolong the in vivo circulation time of the protein and retain its osteoblastic activity without any appreciable cytotoxicity.
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Advantages
- This invention allows further development of NELL-1 into an effective systemic therapy for the treatment of osteoporosis. NELL-1 can be administrated with a low dose and low frequency, possibly leading to lower treatment costs and higher patient compliance.
- Unlike BMP-2 which has undesirable side effects such as excessive and ectopic bone formation, bone resorption, etc., NELL-1 has fewer side effects occurring during application in vivo.
Potential Applications
A principal application of this invention is for the treatment of osteoporosis.
Contact Information
Name: UCLA Technology Development Group
Email: ncd@tdg.ucla.edu
Phone: 310.794.0558