Researchers discover a homing peptide that activates drug delivery in skin tissue
“The purpose of our drug development programme is to develop tissue-specific medicine that would allow systemically administered therapies to be targeted exclusively to the skin. In this way, the possible side effects of drug treatment in other tissues would be eliminated,” says Professor Tero Järvinen from Tampere University who leads the study.
“The drug we are developing actively seeks out diseased tissue through circulation. This is possible because each of our tissues leaves its own molecular level “fingerprint” in the blood vessels of tissues. In this way, our body has a system like postal coding between different tissues, which allows the drug to be sent to the correct “postal code” in the target tissue. These target-specific “vascular zip codes” can be exploited in regenerative medicine and we were the first in the world to find the “skin postal code”,” Järvinen says.
The study screened a library of one billion different peptides made up of pieces of protein, or peptides, using the in vivo phage display method, and finally found a peptide that is applied to the skin through the bloodstream. The peptide is named the tCRK peptide according to its amino acid sequence.
The multifunctional drug molecule developed as a result of the study has two functional units: a therapeutic protein and a peptide now identified as an address label. The multifunctional drug, i.e. the fusion protein, applied to the skin by the peptide, is significantly more active biologically than the original drug molecule.
“When this recombinant fusion protein was tested in animal experiments, we showed that mice with the deadly skin disease epidermolysis bullosa survived longer than with any other drug tested to date,” Järvinen says.
The research was conducted in Professor Tero Järvinen’s research group at Tampere University. The Department of Dermatology at New York Medical College has been the main partner, but researchers from the universities of Helsinki and Tartu have also been involved.
The researchers will continue to cooperate in the hopes of advancing the therapeutic multi-functional recombinant protein to clinical trials in RDEB patients under the Orphan Drug Act at NY Medical College.
“We believe that our technology also has indications for the treatment of other dermatological conditions, skin wound healing, and issues related to plastic surgery,” Järvinen notes.
The results of the study were published in the international Molecular Therapy journal.
Toini Pemmari, Larisa Ivanova, Ulrike May, Prakash Lingasamy, Allan Tobi, Anja Pasternack, Stuart Prince, Olli Ritvos, Shreya Makkapati, Tambet Teesalu, Mitchell S. Cairo, Tero A.H.Järvinen/ Yanling Liao: Exposed CendR domain in homing peptide yields skin-targeted therapeutic in epidermolysis bullosa. 2020. Molecular Therapy
https://doi.org/10.1016/j.ymthe.2020.05.017
Enquiries:
Professor Tero Järvinen, tero.jarvinen [at] tuni.fi
MEDIA RELEASE BY TAMPERE UNIVVERSITY 26 May 2020
