28 DRUG DISCOVERY AND DEVELOPMENT


Midkine treatment reduces heart muscle death by 27 per cent


Cellmid Limited has completed its milestone preclinical studies into the efficacy of midkine (MK) for the treatment of acute myocardial infarction (AMI). Total dose of 0.18 mg/ kg MK performed best and reduced the area of heart muscle damage by approximately 27 per cent when compared with untreated animals undergoing the same procedure. Acute myocardial infarction (AMI),


Gary Smith, leader of the cell-line derivation project and co-director of the UM Consortium for Stem Cell Therapies.


Photograph Courtesy Scott Soderberg/U-M Photo Services.


experience symptoms in adolescence or early adulthood.


“Te creation of these cell lines will provide a new tool that will help the international scientific community improve the treatment of these diseases,” said Sean Morrison, director of the UM Center for Stem Cell Biology.


Cell-line derivation Te U-M cell-line derivation project was approved by the university’s Human Pluripotent Stem Cell Research Oversight Committee and the Medical School’s Institutional Review Board. Both committees are composed of physicians, scientists, ethicists, attorneys and community members who concluded that the project would be conducted ethically, legally and to the benefit of patients.


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“Tis scientific breakthrough demonstrates the wisdom of the voters of Michigan, who realised the importance of stem cell research for the health and well-being of the state,” said A Alfred Taubman, founder and chair of the A Alfred Taubman Medical Research Institute.


“We have become global leaders in the science of stem cells,” he said. “We are producing tools that can be of immeasurable aid to scientists studying such disorders as hemophilia and Huntington’s disease.


“And we are just beginning to scratch the surface of this new scientific frontier.”


University of Michigan is based in Ann Arbor, MI, United States. www.umich.edu


or heart attack, is the death of heart muscle (myocardial) cells. AMI is the leading cause of death worldwide. In Australia around 30 000 people die from heart attack every year accounting for 22 per cent of all deaths. In the US more than 1 000 000 people are affected annually with ~250,000 deaths. AMI occurs when blood vessels to the heart muscle become blocked, preventing oxygen reaching the cells. Without intervention myocardial damage exceeds a threshold and prevents the cells from carrying out their normal self-repair functions. Currently there are limited treatment options to prevent the death of myocardial cells either during or after a heart attack. Midkine (MK) is part of a natural


defence mechanism activated during heart attack. Heart muscle cells under stress from a lack of oxygen begin to produce MK in an attempt to prevent cell death. However, the amount of MK that AMI-affected cells can produce is very limited and the time taken to produce it is slow. Administration of Cellmid’s MK, a validated cell protecting agent, is expected to directly reduce cell death from myocardial injury and therefore improve immediate and long term survival of heart attack patients. Midkine 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 ischemia, cancer, inflammation,


autoimmunity, nerve growth/repair and wound healing. Midkine is barely detectable in healthy adults and high expression levels only occur as a consequence of the pathogenesis of a number of different disorders. These studies confirm Cellmid’s


own earlier research findings that MK does indeed reduce heart damage due to ischemia and reperfusion injury. The significant improvement


demonstrated by the studies’ results mean that large animal trials can now commence. Further, manufacturing of GMP quality MK can also proceed in preparation for clinical trials. The preclinical study was


conducted by Cellmid’s collaborator, Pharmahungary, within their specialist cardiovascular research facilities. MK was given to rats intravenously in single doses and in follow up intravenous infusions. MK was also safe and well tolerated, with no difference in adverse events between MK treated and untreated controls. “A reduction of around 27 per cent


in infarct size is very encouraging”, said CEO of Pharmahungary, Dr Peter Ferdinandy. “Pharmahungary’s study was extremely rigorous. Samples were blinded for analysis and the area of heart muscle death was measured using their state-of-the-art imaging software Infarctsize,” added Cellmid’s Head of Product Development, Darren Jones. As well as conducting the pivotal


MK efficacy study, Pharmahungary also evaluated MK in dose-ranging and acute safety/tolerability studies. Dose- ranging studies showed that MK was effective at significantly reducing heart muscle death with doses between 0.1mg/kg and 1.0 mg/kg. Furthermore, MK was safe and well tolerated at doses 16 times greater than the most effective dose of 0.18 mg/kg, with no cardiovascular toxicities observed.


For more information, visit www.cellmid.com.au


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