cellmid-5

Midkine

 
     
  • Extensively validated therapeutic and diagnostic target
  • Well understood structure and function with over 750 peer-reviewed scientific publications 
  • High midkine levels associated with disease state in cancer and inflammatory conditions and only occur during disease
  • Multiple mechanisms that promote cancer and inflammation
  • Early and sensitive biomarker of disease
Top: Midkine solution structure and surface chemistry (Lim et al., 2013)            
 Bottom: Midkine bound to Chondroitin sulphate (Solera et al., 2016)            


Discovered in 1988 by Professors Takashi Muramatsu and Kenji Kadomatsu, MK is a multifunctional growth factor that is highly expressed during embryonic development. Midkine modulates many important biological interactions such as cell growth, cell migration and cellular adherence. These functions are relevant to chronic inflammatory conditions, fibrosis, autoimmunity, cancer, ischemia, nerve growth/repair and wound healing. Midkine expression is often evident very early in disease onset, even before any apparent physical symptoms, and increases in midkine levels often correspond to increased disease severity. Accordingly, midkine is an important predictive and prognostic marker in cancers and inflammatory diseases.  As midkine is barely detectable in healthy adults, these predictive and prognostic tests have high sensitivity and specificity, and correspondingly, because midkine is only significantly present in a disease context, targeting midkine is not expected to harm normal healthy tissues. Cellmid’s scientists have published nearly 250 peer-reviewed journal articles describing midkine’s structure, functions, receptors and methods of action. Midkine is a well understood, validated target for treating and diagnosing many significant human diseases. 

 

Midkine recruits inflammatory leukocytes into tissue. Immobilised MK on the luminal surface of blood vessels  arrests rolling neutrophils, enabling their  transfer from circulation into tissue.  Cell arrest occurs via high affinity MK-LRP-1 interaction. Since many cancer cells express high levels of LRP-1, this mechanism may also explain MK’s observed pro-metastatic effects.   

 

 

Midkine and receptor interactions. Midkine is a modulator of cell signalling. There is evidence of this activity via a variety of receptors under different inflammatory and disease settings.

 

Protein Production

Cellmid, through contract arrangements, manufactures recombinant midkine protein for its research arms.   The Company holds both composition of matter and methodological patents around the production of midkine protein, and its use as therapeutic in coronary heart disease.   Cellmid is currently investigating avenues towards GMP manufacture of recombinant midkine to enable clinical trials after the pre-clinical phases have been completed.


Therapeutic Antibody Production

Cellmid holds a number of methodological and composition of matter patents around therapeutic antibodies to midkine, their production, and use in a number of disease indications.  The Company currently produces a number of murine antibodies to various regions of the human midkine protein.  The antibodies are used in Cellmid’s pre-clinical programs in inflammatory and fibrotic diseases and cancer, as well as in Cellmid's ELISA kit for the detection of midkine in serum and plasma.  Several of the antibodies have been humanised and are being developed towards GMP manufacture.