Diamyd Medical’s diabetes vaccine and regenerative medicine in synergy
Diamyd Medical (Nasdaq Stockholm First North, DMYD B) is the largest shareholder in Cellaviva AB, which is Sweden’s first biobank for private family preservation of, and research on, stem cells from the umbilical cord. In conjunction with the election of Anders Essen-Möller, Diamyd Medical’s principal owner, as the new Chairman of the Board for Cellaviva, clarification is provided herein of Diamyd Medical’s views on the synergies between the companies.
Diamyd Medical is dedicated to finding a cure for type 1 diabetes. The strategy is in part to use Antigen Based Therapy (ABT), such as the diabetes vaccine Diamyd®, to halt the autoimmune attack on insulin-producing beta cells, and in part to restore beta-cell function through measures including e.g. transplantation of autologous umbilical cord mesenchymal stem cells.
“Patients with type 1-diabetes have killer cells that destroy insulin producing cells. This is true for both transplanted islets or cell therapy with insulin producing stem cells – the killer cells do their job,” says Professor Åke Lernmark, Lund University, Sweden, and scientific adviser to Diamyd Medical. “A combination treatment is necessary. The first step is to induce immune tolerance with Antigen Based Therapy. When tolerance is established, for example for the GAD-molecule, the next step is to administrate insulin producing stem cells. It should be valuable to save stem cells from the umbilical cord to enable this form of combination therapy with the patient’s own (autologous) cells”.
“Diamyd Medical’s interest in Cellaviva stems from the conviction that autologous stem cells will be of decisive significance in curing type 1 diabetes, as well as many other injuries and disorders,” says Anders Essen-Möller, President and CEO of Diamyd Medical. “With investments into Cellaviva we want to reach out and together with the society support and bring this type of research forward. To enable that young and autologous stem cells can be used for treatment of the respective individual or perhaps a sibling, Cellaviva is offering the preservation of stem cells from the umbilical cord as a service. It is the hope of Diamyd Medical that this – perhaps gradually for certain risk groups – eventually will become an approved regimen within the Swedish health care system,
Within the wide general scope of applications in which stem cells can be expected to be utilized, in this press release we have limited ourselves to analyzing a few questions that apply to type 1 diabetes”.
a) Can mesenchymal stem cells cure type 1 diabetes?
b) Are autologous stem cells better than other sources of stem cells (allogenic)?
c) Are early umbilical cord mesenchymal stem cells better than older bone marrow derived mesenchymal stem cells?
d) Does it make financial sense to preserve umbilical cord stem cells in families with type 1 diabetes?
A. CAN MESENCHYMAL STEM CELLS CURE TYPE 1 DIABETES?
Professor Per-Ola Carlsson, Uppsala, Sweden, showed that treatment with autologous stem cells is a promising method for retaining the insulin-producing function of beta-cells in patients with newly onset type 1 diabetes (Diabetes 2015). Twenty adult patients were randomly assigned to either an active group, receiving autologous mesenchymal stem cells taken from the bone marrow, or to a control group. After a period of one year, the beta-cell function in the group receiving active treatment had either improved or been maintained, but had declined in the control group. The conclusion following the clinical trial was that treatment with autologous mesenchymal stem cells comprises a safe and promising strategy for intervention in the disease process and the preservation of beta-cell function in patients recently diagnosed with type 1 diabetes.
Jianxia Hu, M.D., Qingdao, China, reported positive results from a study in which patients with newly onset type 1 diabetes were treated with mesenchymal stem cells from umbilical cord tissue known as Wharton’s jelly (Endocrine Journal, 2013). Twenty-nine patients were randomly assigned to either an active group or to a control group. Two years after treatment, both HbA1c and C peptide in the active group were significantly better than pre-treatment as well as compared with the control group post-treatment. The conclusion was drawn that the transplantation of Wharton’s jelly derived mesenchymal stem cells can restore beta-cell function over a longer time period and that this could be an effective method for treatment of type1 diabetes.
Ilona Kalaszczynska, Associate Professor, Warsaw, Poland, reviews the role of Wharton's jelly derived mesenchymal stem cells, and notes that mesenchymal stem cells in general can differentiate not only into cells with mesodermal origin such as bone, cartilage, fat, cardiomyocytes, muscle fibers, renal tubular cells, but can also break germ layer commitment and differentiate into cells of ectodermal origin such as neurons, and of endodermal origin such as hepatocytes and pancreatic islet cells (Biomed Res Int. 2015). The majority of the following references were gathered from Kalaszczynska’s comprehensive review, in which a large volume of information from different research scientists has been compiled.
B. ARE AUTOLOGOUS STEM CELLS BETTER THAN OTHER SOURCES OF STEM CELLS (ALLOGENIC)?
Although Weiss (Stem Cells, 2008) reported that Wharton's jelly derived mesenchymal stem cells may be used in allogeneic transplantations without prior HLA matching , the question remains whether this is valid also after differentiation into tissue specific cells intended for use in regenerative therapy. Huang (Circulation, 2014) reported increased immunogenicity of bone marrow mesenchymal stem cells upon endothelial and myogenic differentiation with a shift in the expression of the transplantation antigens MHC-I and MHC-II.
Ingham (Journal of Tissue Engineering, 2014), reported from preclinical studies that stem cells used in therapeutic applications where tissue or organ regeneration are involved, require mesenchymal stem cells that are differentiated into tissue-specific cells. However, differentiation has been reported to lead to the loss of both immunosuppressive properties and immunoprivileged status, and this would be a major concern for clinical applications. See further references here below.
Technau (Cytotherapy 2011). Adipose tissue-derived stem cells show both immunogenic and immunosuppressive properties after chondrogenic differentiation.
Chen (Stem Cells, 2007). Chondrogenic differentiation alters the immunosuppressive property of bone marrow-derived mesenchymal stem cells, and the effect is partially due to the upregulated expression of B7 molecules.
C. ARE EARLY UMBILICAL CORD MESENCHYMAL STEM CELLS BETTER THAN OLDER BONE MARROW STEM CELLS?
Song Wu (Nature, 2016), showed that environmental factors cause 70-90 percent of cancer mutations, which means that umbilical cord mesenchymal stem cells, which have not had time to divide as many times, are preferable to older bone marrow stem cells in stem cell treatment.
Kalaszczynska et al concludes that the lifelong perseverance of adult mesenchymal stem cells in the body makes them particularly susceptible to the accumulation of cellular damage, which can lead to cell death, senescence, or loss of regenerative function and in extreme cases to neoplastic transformation. In contrast, neonatal mesenchymal stem cells such as Wharton's jelly derived mesenchymal stem cells in their short, prenatal life are spared from proaging factors. Taken together, the clinical implication of oxidative stress, telomere length, DNA damage and disease is impaired therapeutic potential of mesenchymal stem cells isolated from aged patients; make Wharton’s jelly an ideal source of mesenchymal stem cells and a promising therapeutic agent in regenerative medicine (Biomed Res Int, 2015).
Ting (Stem Cells and Development, 2014), reported that early mesenchymal stem cells have better myogenic potential and engraftment properties than bone marrow derived mesenchymal stem cells.
Bustos (The American Journal of Respiratory and Critical Care Medicine, 2014), reported that mesenchymal stem cells from aged bone marrow lack the anti-inflammatory effect indicating an age-related decline in immunomodulatory activity.
Elevated Free Fatty Acid levels in obese individuals may lead to irreversible changes in mesenchymal stem cells from bone marrow and adipose tissue (Park, Tissue Engineering and Regenerative Medicine, 2013).
Not applying to Wharton’s jelly derived MSC, exposure of adult mesenchymal stem cells during the lifetime to intrinsic (e.g., inflammatory mediators) and extrinsic factors, for example, nonsteroidal anti-inflammatory drugs (NSAIDs) may greatly inflect their viability or plasticity (Muller, Cell biology International, 2011).
Fan (Rejuvenation Research, 2010), showed that the regenerative capacity of human mesenchymal stem cells from 1-5 year olds outperformed mesenchymal stem cells from 50–70 olds.
Hermann (Cytotherapy, 2010), reported that unlike mesenchymal stem cells from young individuals, mesenchymal stem cells from elderly individuals could not be differentiated into neuro-ectodermal cells. This makes adult bone marrow derived stem cells unsuitable for autologous cell replacement for neurologic diseases in elderly patients.
Stenderup (Bone, 2003); Huang (Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2005) and Stolzing (Mechanisms of Ageing and Development, 2008), separately reported that age of donor tissue affects several properties of mesenchymal stem cells. As older mesenchymal stem cells may have accumulated cellular damages, leading to cell death, senescence, loss of regenerative function, and neoplastic transformation, neonatal mesenchymal stem cells such as from Wharton’s jelly are spared from proaging factors.
D. DOES IT MAKE FINANCIAL SENSE TO SAVE UMBILICAL CORD STEM CELLS WHEN RELATIVES HAVE TYPE 1 DIABETES?
Umbilical cord stem cells may come to be used for the treatment of several disorders and injuries. However, for now, we will only look at type 1 diabetes. Let us also assume that Diamyd Medical’s development approach is correct, i.e. that one can cure type 1 diabetes by using umbilical cord stem cells together with Antigen Based Therapy (ABT). If so, does it make financial sense to save umbilical cord stem cells where, for instance, the father has type 1 diabetes?
In Sweden, the risk of a child developing type 1 diabetes is about 1.5 percent. If the mother has type 1 diabetes, the risk of a child developing type 1 diabetes is about 3 percent. If the father has type 1 diabetes, the risk increases to about 5 percent. In a family with two children, where one child develops type 1 diabetes, the risk is 8 percent that the second child will also develop type 1 diabetes (Ake Lernmark, verbal communication). If a father with type 1 diabetes has two children, the risk that at least one child will develop type 1 diabetes is about 10 percent. Since siblings have at least 25 percent and at most 100 percent common transplantation antigens – i.e. antigens that can cause rejection of foreign tissue – and since stem cells in themselves have immuno-modulating effects, it is anticipated in this example that umbilical cord stem cells is primarily saved from one child per family.
The cost for storing umbilical cord stem cells, during twenty years, from one child from ten different families where the fathers have type 1 diabetes is about SEK 400,000. If each family has two children and saves the umbilical cord from one child, and the risk is 10 percent that a minimum of one child will develop type 1 diabetes, it is expected that among these 10 families at least one child will develop type 1 diabetes. In the above scenario, it would cost the healthcare system SEK 400,000 to keep stem cells available for those in this risk group that develop type 1 diabetes.
Curing a type 1 diabetes patient in this risk group requires a further sum of about SEK 150,000 in costs for Antigen Based Therapy (ABT) with, for example, Diamyd® or an equivalent (that stops the autoimmune process), and a possible further cost of about SEK 300,000 in conjunction with the transplantation of stem cells (to restore the mass of insulin-producing cells). This means that it could cost a total of SEK 850,000 to cure a patient with type 1 diabetes in this risk group. In comparison, the current cost of treating other serious disorders, often exceeds SEK 1 million – per year.
About Cellaviva AB
Cellaviva is Sweden’s first biobank for family preservation of and research on stem cells from the umbilical cord. Stem cells from the umbilical cord are collected at birth, analyzed, frozen, and saved for possible future use. Every cell in the body is stemming from stem cells that have unique properties, which make them attractive from a medical perspective. The operations work under approval from the Swedish Health and Social Care Inspectorate (IVO). Read more at www.cellaviva.se.
About Diamyd Medical
Diamyd Medical is dedicated to finding a cure for autoimmune diabetes through pharmaceutical development and investments in stem cell and medical technology.
Diamyd Medical develops the diabetes vaccine Diamyd®, an Antigen Based Therapy (ABT) based on the exclusively licensed GAD-molecule. The Company’s licensed technologies for GABA and Gliadin have also potential to become key pieces of the puzzle of a future solution to prevent, treat or cure autoimmune diabetes, and also certain inflammatory diseases. At this time six clinical studies are ongoing with Diamyd®. Diamyd Medical is with its holdings of 39% one of the major shareholders in the stem cell company Cellaviva AB. Stem cells can be expected to be used in Personalized Regenerative Medicine (PRM), for example for restoration of beta cell mass in diabetes patients where the autoimmune component of the disease has been arrested. Diamyd Medical also has holdings in the medtech company Companion Medical, Inc., San Diego, USA and in the gene therapy company Periphagen, Inc., Pittsburgh, USA.
Diamyd Medical’s B-share is traded on Nasdaq Stockholm First North under the ticker DMYD B. Remium Nordic AB is the Company’s Certified Adviser.
For further information, please contact:
Anders Essen-Möller, President and CEO
Phone: +46 70 55 10 679. E-mail: anders.essen-moller@diamyd.com
Diamyd Medical AB (publ)
Kungsgatan 29, SE-111 56 Stockholm, Sweden. Phone: +46 8 661 00 26, Fax: +46 8 661 63 68
E-mail: info@diamyd.com. Reg. no.: 556242-3797. Website: www.diamyd.com.
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