Gil Van Bokkelen Ph.D. Chairman and CEO of Athersys needs to make Multistem for late stage pulmonary tuberculosis (TB) patients a top priority. This can be done as an investigator(s) sponsored trial. This indication aligns very well with ARDS and sepsis.
I am extremely enthusiastic about this indication because Dr. Maeurer and Dr. Zumla are world class physicians who understand TB. They understand how MSCs (or Multistem) can make a contribution by (Int J Infect Dis. 2015 Mar;32:32-8):
1. Offering late stage salvage therapy options for patients with drug-resistant TB who would otherwise die.
2. Increase patient's anti-M.tuberculosis directed immune response
3. Possibly shorten the duration of anti-TB therapy
Multistem can make this contribution in a way that is profitable because of many funding sources for TB.
You can find the Phase 1 study by googling DRKS-ID: DRKS00000763.
Markus Maeurer MD, PhD
Professor of Clinical Immunology, Head of the Division Therapeutic Immunology at
LabMed, KarolinskaInstitutet and Senior Physician at the Center for allogeneic stem
cell transplantation, CAST. He hold degrees to practice medicine in Sweden, Germany, Switzerland and the US (ECFMG) and has been appointed a Fellow of the Royal Chamber of Physicians (FRCP,London).
Prof Alimuddin Zumla
Professor Zumla is an honours graduate of the University of Zambia and the University of London. He is dually qualified in medicine (MBChB) and science (PhD) and is accredited in internal medicine, infectious diseases and clinical immunology. Professor Zumla is a Fellow of the Royal Colleges of Physicians of London and Edinburgh, Fellow of the Royal College of Pathologists and a Fellow of the Royal Society of Biology.
11.18.2015 Geron at the Stifel 2015 Healthcare Conference
Can Multistem Cure Late Stage Tuberculosis (TB)?
The Lancet Respiratory Medicine (Volume 2, No. 2, p108–122, February 2014)
SAN FRANCISCO, May 5, 2015 /PRNewswire/ -- Silver Creek Pharmaceuticals, Inc. announced today the award of a Small Business Innovation Research (SBIR) grant from the National Institute of Health (NIH).
Silver Creek is a San Francisco based biotechnology company that discovers and develops targeted protein therapeutics to selectively repair tissues damaged by disease. This award will be used to advance their proprietary protein therapeutics engineered to repair heart tissue following a heart attack.
Silver Creek's Smart Growth Factors (SGFs) are designed to selectively activate growth factor receptors in tissues damaged by disease, resulting in highly localized therapeutic benefits while also avoiding undesirable side effects. The therapeutics are currently in preclinical development to study their effects in regenerating tissues damaged by heart and kidney disease. "While growth factors have long been known to activate tissue repair mechanisms in preclinical research, growth factor-based therapies have been fundamentally limited by their short circulation time and off-target effects," said Matt Onsum, President and CEO of Silver Creek Pharmaceuticals. "Silver Creek's Smart Growth Factor technology has demonstrated sustained and local activation of growth factor mediated repair mechanisms in preclinical research. Silver Creek's technology holds great promise for unlocking the potential of growth factors as therapeutics, including treatment of devastating diseases such as heart and kidney disease. We are pleased that this grant from the NIH will help us further develop therapeutic solutions for patients in these indications."
April 1st, 2014– The United States Patent Office issued Silver Creek’s patent “Bi-specific Fusion Proteins” (US20110286976 A1) which broadly covers our platform technology and molecules for repairing tissue damaged by disease.
THERE ARE ZERO THERAPIES REPAIR DAMAGED HEARTS - Current therapies only manage the symptoms of heart disease. Our goal is create therapies that enhance the body's healing response and repair damaged tissue
Bi-specific fusion proteins with therapeutic uses are provided, as well as pharmaceutical compositions comprising such fusion proteins, and methods for using such fusion proteins to repair or regenerate damaged or diseased tissue. The bi-specific fusion proteins generally comprise: (a) a targeting polypeptide domain that binds to a target molecule; and (b) an activator domain that detectably modulates tissue regeneration.
For 2 animals per treatment group, the animals were perfused with normal saline. The heart was isolated and the left ventricle was washed with saline. The heart was trimmed down to just the left and right ventricles, and dissected into four pieces as shown FIG. 6.1. The pieces were collected, weighed, flash frozen (in liquid Nitrogen), then stored in labeled microcentrifuge tubes (one sample per tube, hence 4 samples per heart) at −80° C. and shipped to Silver Creek Pharmaceuticals on dry ice.
Circulation. 2012 Feb 7;125(5):685-96. doi: 10.1161/CIRCULATIONAHA.111.070508. Epub 2012 Jan 5.
The bispecific SDF1-GPVI fusion protein preserves myocardial function after transient ischemia in mice.
Keep the faith Yags!!!
Athersys has found its calling; it won't be long now.
I am looking forward to progress for:
1. Acute respiratory distress syndrome (ARDS) progress (currently preparing for the launch of this trial)
2. Sepsis (The most common cause of ARDS is sepsis: Source Mayo Clinic)
3. Pulmonary tuberculosis (TB)
For the quarterly period ended September 30, 2015
Acute Respiratory Distress Syndrome : We were awarded a grant for up to approximately £2.0 million to support an initial trial to treat patients suffering from acute respiratory distress syndrome, or ARDS. ARDS is a serious immunological and inflammatory condition characterized by widespread inflammation in the lungs.
ARDS can be triggered by pneumonia, sepsis, or other trauma and represents a major cause of morbidity and mortality in the critical care setting. The medical need for a safe and effective treatment of ARDS is significant due to its high mortality rate, and it annually affects approximately 400,000 to 500,000 patients in Europe, the United States and Japan, together.
The grant supporting this Phase 2a clinical trial was awarded by Innovate UK to our subsidiary, Athersys Limited in the United Kingdom, or UK, in conjunction with Catapult. We are currently preparing for the launch of this trial.
FACT: TB now ranks alongside HIV as a leading cause of death worldwide.
FACT: In 2014, TB killed 1.5 million people (1.1 million HIV-negative and 0.4 million HIV-positive). The toll comprised 890 000 men, 480 000 women and 140 000 children.
FACT: Of the 480 000 cases of multidrug-resistant TB (MDR-TB) estimated to have occurred in 2014, only about a quarter of these – 123 000 – were detected and reported.
***Multistem can help late stage and difficult TB cases.
who int tb publications global report gtbr 2015
FACT: For MDR-TB US$ 1.3 billion is needed each year (WHO GF TB financing factsheet).
FACT: "The Global Fund" provides the largest international donor funding stream for TB efforts.
FACT: Multistem can help the most difficult and expensive late-stage pulmonary TB cases: The experts have published results in The Lancet Respiratory Medicine (Volume 2, No. 2, p108–122, February 2014).
The results for MSCs for TB (phase I) are:16 of the 30 patients receiving MSCs cleared TB infection by 18 months. Only 5 of 30 not treated with stem cells cleared.
Multistem for late stage pulmonary tuberculosis (TB) is Dr. Gil Van Bokkelen's to lose.
The experts have published results in The Lancet Respiratory Medicine (Volume 2, No. 2, p108–122, February 2014).
The results for MSCs for TB (phase I) are:
16 of the 30 patients receiving MSCs cleared TB infection by 18 months. Only 5 of 30 not treated with stem cells cleared.
More data is needed while saving lives.
Multistem is more cost effective than autologous mesenchymal stromal cells or allogeneic MSCs such as Prochymal. In addition, Multistem can be given at higher cell counts.
As far as the financial viability of Multistem for late stage pulmonary TB. TB is backed by the World Health Organization, The Gates Foundation, and as an example, from 2000 to 2011 World Bank gave $583 million in direct funding for TB control.
Dr. Gil Van Bokkelen would be doing the world a great service to deploy Multistem for late stage pulmonary TB as rapidly as possible.
There are TB clinics and hospitals around the world ready to do investigator sponsored trials. This is a unique opportunity to showcase what Multistem does best, control pulmonary conditions such as:
1. Acute respiratory distress syndrome (ARDS)
3. Late stage pulmonary tuberculosis (TB)
Let's home that Athersys helps to solve this problem and save lives of TB patients. Google and watch pbs org wgbh pages frontline tb-silent-killer
3. Principle of adjunct MSC treatment for TB (InternationalJournalofInfectiousDiseases32(2015)32–38)
MSCs dampen inflammation through an array of interactions with innate and adaptive immune cells thereby modulating immune responses. MSCs, which constitute ∼0.001% of bone marrow mononuclear cells (proportion declines over age), can be easily expanded ex vivo in culture and when re-infused in patients they home to sites of injury and inflammation promoting tissue repair. The culture conditions, degree of expansion and the final MSCs preparations, may vary influencing clinical outcome.
Enhanced Mtb-antigen specific responses were observed following MSC infusion in a Phase I study conducted in Belarus patients with MDR-TB.40
An ongoing study of adjuvant autologous MSC therapy in South African patients with MDR/XDR-TB is establishing the safety in patients with MDR/XDR TB in Durban, King Dinuzulu Hospital Complex and is investigating immunological mechanisms of anti-TB responses and markers of a response to therapy. Specific efforts have been made to study responses to MSC treatment defined by HR-CT imaging as well as to assess the best incremental value of this adjuvant therapy in the subset of patients who would benefit from this mode of cellular therapy, compared to other possible immune-interventions targeting the host immune response.43
Skrahin, A., Ahmed, R.K., Ferrara, G., Rane, L., Poiret, T., Isaikina, Y. et al. Autologous mesenchymal stromal cell infusion as adjunct treatment in patients with multidrug and extensively drug-resistant tuberculosis: an open-label phase 1 safety trial. The Lancet Respiratory medicine. 2014; 2: 108–122
Kaufmann, S.H., Lange, C., Rao, M., Balaji, K.N., Lotze, M., Schito, M. et al. Progress in tuberculosis vaccine development and host-directed therapies--a state of the art review. The Lancet Respiratory medicine. 2014; 2: 301–320
METHODS OF TREATING OR PREVENTING RESPIRATORY CONDITIONS (10/29/2015)
United States Patent Application 20150306146
The term “respiratory condition” shall be taken to include any disease or condition that reduces lung function in a subject and includes, for example, asthma, chronic bronchitis, emphysema, cystic fibrosis, respiratory failure, pulmonary oedema, pulmonary embolism, pulmonary hypertension (high blood pressure), pneumonia and tuberculosis (TB)
In 1992 FDA instituted the Accelerated Approval regulations. These regulations allowed drugs for serious conditions that filled an unmet medical need to be approved based on a surrogate endpoint.
Multistem Vs. Prochymal for TB: Will Athersys or Mesoblast get there first?
The race is on!