Funding Scientific Research
The Principal Mission of the Life Extension Foundation®
Since its inception in 1980, the Life Extension Foundation (LEF) has conducted scientific research that goes beyond the scope of academic institutions and biomedical companies. The purpose of this research is to identify and validate technologies that can slow and reverse aging and prevent premature death.
Mainstream research today is focused on how to treat heart attacks, cancer, Alzheimer’s disease and strokes. These are the diseases that we generally assume cause death.
What most doctors don’t yet recognize is that these devastating illnesses are caused mostly by aging. The Life Extension Foundation has provided more than $110 million to scientists across the country to look beyond the disease state and instead search for authentic anti-aging and anti-death solutions. Our objective is to prevent or postpone age-related disease, restore health, and enable much longer human life spans.
As you’ll read in this annual report, Life Extension® continues to fund targeted research into killer diseases such as cancer, cardiovascular disorders, immune dysfunction and neurological deficits. These programs are part of a strategic vision to limit or prevent diseases as we mature.
The purpose of this annual report is to enlighten LEF members about the research programs we are funding and detail LEF’s commitment to meaningful scientific discovery.
This research is made possible with proceeds from the dietary supplements you buy from the Life Extension Foundation Buyers Club. Each time you purchase a Life Extension product, you are investing in your future by supporting biomedical research aimed at eradicating age-related disease. No other organization on the planet is funding so many diverse initiatives to enable aging humans to attain very long and healthy life spans.
Accelerating stem cell research
The Life Extension Foundation is helping to fund the development of stem cell technologies designed to eliminate atherosclerosis, which will prevent many premature deaths caused by occlusive arterial disease (coronary atherosclerosis and ischemic stroke).
Pluripotent stem cells (cells capable of creating any type of cell) will be used to differentiate into endothelial progenitor cells that will replace the aged, damaged, and plaque-laden cells on the walls of blood vessels. These new cells will not only be young, but may remain young indefinitely by the use of the telomere-lengthening enzyme telomerase.
When perfected, this technology may enable doctors to inject progenitor cells that will regenerate every tissue in the body, thus restoring aging humans to youthful health and vigor.
The Life Extension Foundation is also providing funding to create and differentiate pluripotent stem cells into immune system cells that could treat patients afflicted with certain cancers and HIV. This technology has the potential to rejuvenate everyone’s immune system.
A grant was made in January 2013 to researchers working at Ichor Therapeutics, Inc. to fund research into developing immune system blood stem cells (hematopoetic stem cells or HSCs) from undifferentiated stem cells. The primary challenge of this project will be to make undifferentiated stem cells develop into the specific HSC stem cell type. Once that objective has been achieved, the second objective will be to get the HSCs to multiply into large numbers of HSCs.
If this research project succeeds, the most immediate benefit will be the ability to extract cells from patients with compromised immune systems (such as patients with cancer), induce those cells to become undifferentiated stem cells, re-differentiate those cells into HSCs, expand the HSCs to become plentiful, and then administer the plentiful HSCs to patients from whom the original cells were taken —without fear of immune system rejection.
This stem cell therapy is designed to regenerate/rejuvenate tissues that have been damaged or become senescent. The advantage of using stem cells derived from the patient’s own tissue is that they will not be rejected due to immune system incompatibility (as would happen if the cells were derived from another person).
The success of this project has the potential to not only benefit patients suffering from HIV and immune system cancers, but to rejuvenate the immune systems of the elderly. Because of immune system aging, a person over age 65 is about a hundred times more likely to die from an influenza-related death than a person who is between the ages of 5 and 49.1
Find a way to live beyond 100 years in good health
Super-centenarians are people who live 110 years and beyond, usually in relatively good health. They appear to have better genes than the rest of us, and understanding the differences could be the key to allowing anyone to reach those ages.
The Life Extension Foundation is funding a project by James Clement and Parijata Mackey to travel in the USA and abroad collecting DNA samples from people who have lived longer than 105 years. Their goal is to determine what is genetically different about these very long-lived individuals that allowed many of them to live extremely long lives without cancer, diabetes, cardiovascular diseases, or Alzheimer’s.
James Clement and Parijata Mackey are working with Dr. George Church of Harvard Medical School to sequence and analyze the whole genomes of these “super-centenarians” in the hope of discovering what genes confer such health and longevity. The goal of cataloging this knowledge is to help find ways to bring such health and longevity benefits to everyone – so we can all become super-centenarians.
Cancer kills 1,500 Americans every day.2 These deaths occur — to a great extent — because of an antiquated but entrenched treatment system that relies on chemotherapy, radiation and surgery. Millions more are still alive, but survive with long-term treatment side effects, shortened life spans, and the omnipresent prospect of a cancer recurrence. Our war on cancer is just beginning.
In our quest to control human aging, Life Extension Foundation is committed to reducing these appalling deaths from malignancies. Our support of innovative cancer research is one critical means to this end.
Life Extension has launched a Phase I/II clinical trial to determine if the generic drug dichloracetate (DCA) is able to induce partial and/or complete remission in cancer subjects with a variety of malignancies. The three-month trial is taking place at a highly-regarded private clinic in the Caribbean, and is open to 40-60 participants who have failed conventional or investigational cancer therapies and have few options for further treatment. The DCA dosing is orally-administered twice daily, five days a week for 12 weeks. Participants also receive optimized nutritional supplements.
DCA is a metabolic modulator that retards the breakdown of glucose to lactic acid, interfering with the glucose uptake that is crucial to cancer cell survival. By suppressing the enzyme PDK (pyruvate dehydrogenase kinase), DCA disrupts aerobic glycolysis and essentially starves cancer cells of glucose, their primary fuel, which in turn induces apoptosis (normal cell death), decreases cancer cell proliferation, and inhibits tumor growth.3 DCA’s low toxicity produces only mild side effects at effective doses, with peripheral neuropathy being the most commonly reported adverse side effect. 4
Of the hundreds of studies published about DCA in the past 30 years, most relate to its use in treating the rare childhood disease congenital lactic acidosis. Only about a dozen, mostly in vitro studies have documented DCA’s efficacy as an anti-cancer agent, with several in vivo studies showing that DCA can induce apoptosis in epithelial ovarian cancer cells5 and malignant brain tumors.6 DCA was able to upregulate the apoptotic function by depolarizing the mitochondria and increasing mitochondrial reactive oxygen species.7
Adding to the record about this powerful metabolic intervention agent is a December 2012 peer-reviewed published case report by LEF associates Stephen Strum, M.D., and Orn Adalsteinsson, Ph.D., et al, documenting a complete remission of more than four years to date in a non-Hodgkin’s lymphoma patient who used DCA as a monotherapy after his cancer had progressed following conventional chemotherapy.8
Meanwhile, LEF is planning to continue with cell line studies at the University of Arkansas Medical Center to evaluate the effects of DCA when it is used in conjunction with conventional chemotherapy combinations against lymphoma and triple negative breast cancer cells.
Replenishing the immune system with the essential building blocks it needs to effectively attack cancer is the goal of several immunotherapy treatments LEF and International Strategic Cancer Alliance (ISCA) are investigating, which rely on the body’s innate ability to heal itself.
In the case of a vitamin D cofactor called Gc macrophage activating factor (GcMAF), LEF is exploring further clinical investigation into its additive or synergistic effects when used with dichloracetate (DCA). GcMAF has demonstrated some complete remissions on its own in patients who participated in three separate trials on breast,9 prostate,10 and colorectal cancer.11 The mechanism of action involves resupplying the Gc protein (also known as vitamin D binding protein), which cancer cells destroy by secreting an abundance of the enzyme Nagalase.12 GcMAF restores the deficiency, which is a critical component in activating the macrophages, the immune system’s cancer scavengers. It is interesting that vitamin D has such a potent anti-tumor effect that cancer cells produce the enzyme (Nagalase) to prevent vitamin D from binding to cancer cells. GcMAF disables the ability of cancer cells to shield against vitamin D.
While DCA and GcMAF have very different mechanisms of action – DCA restores mitochondrial metabolism, while GcMAF activates tumoricidal macrophages — the combination may prove to be a potent anti-cancer weapon by fighting the war simultaneously on two fronts. We are carrying out an investigational study to address the combination of the two products.
In order to determine the efficacy of GcMAF, we can measure the serum Nagalase concentration. When GcMAF is effective, the macrophage activation (MAF) is increased and tumor burden is decreased, as indicated by reduced serum Nagalase levels.9-11
Obtaining supplies of GcMAF were problematic in the past, but we are now pleased to report that this difficulty has been resolved, which will allow us to expand our investigational efforts in the Caribbean in the coming year.
Leukocyte Infusion Therapy
Leukocyte infusion therapy is one of the new cancer immunotherapies designed to stimulate the immune system to destroy tumors. The original animal studies were carried out by Dr. Zheng Cui of Wake Forest University, who found that a subpopulation of leukocytes (white cells) called granulocytes are primarily responsible for killing cancer cells.13,14 In order to evaluate leukocyte infusion therapy in humans, Life Extension Foundation provided two large grants for Phase I/II clinical trials. These trials are now under way for a maximum of 29 patients with metastatic, nonhematological cancers under the direction of Dipnarine Maharaj, M.D., at the South Florida Bone Marrow/Stem Cell Transplant Institute in Boynton Beach, Florida.
Granulocytes from the blood of healthy human donors are concentrated for infusion into the study participants. Because four to six donors are needed for each subject, a Donor Registry was established with strict eligibility criteria, including screening for infectious diseases and other blood testing; approximately 100 donors are currently registered.
To date, eight cancer patients with advanced solid tumors of the colon, breast, esophagus, ovaries and prostate have undergone treatment of which two have completed the treatment. Each subject received a total of four granulocyte transfusions, which were well-tolerated. The protocol calls for the treatment of 20 study subjects before any conclusions can be drawn about the effectiveness of the therapy. The trial’s four endpoints are dose response at 90 days, tolerance, safety and efficacy. The response at 90 days after the last infusion will be based on comparison of tumor measurements at baseline. Given the success of the original animal studies conducted at Wake Forest University which were able to cure animals of cancer, Dr. Maharaj is seeking similar results when leukocyte infusion therapy is used in humans.15
Laser Assisted Immunotherapy
Laser-assisted immunotherapy (LIT), the innovative procedure carried out by Dr. Adalsteinsson and his team, continues to produce positive outcomes from an ongoing out-of-country trial for metastatic breast cancer patients. Results to date document that the novel laser therapy combined with the administration of an immunoadjuvant has the potential to both destroy primary tumors and to act as an autologous tumor vaccine.16
Study participants were Stage III and IV late-stage breast cancer patients who had failed conventional or investigational treatments, and had limited options for further therapy. Two courses of LIT treatments were administered to the primary tumor area over two weeks using an 805-nm near-infrared laser and the photosensitizer indocyanine green, followed by injections of the immunoadjuvant (glycated chitosan) to stimulate immunological response. Early study results confirmed good safety, tolerance and low toxicity, with mild adverse reactions occurring only in the treatment area from photothermal injury and local administration of the immune-adjuvant drugs. No grade 3 or 4 side effects were observed. Follow-up to establish treatment efficacy over a one-year period included physical examinations and PET/CT scans.
The first clinical study in the Caribbean has been completed. Of the 15 women study subjects, a total of 12 experienced remission or extensive reduction of primary tumors, and all of them experienced either complete or significant reductions in distant metastases in the lungs, liver, bone, and the brain, indicating a strong systemic response to the treatment. Today, at an average of 31 months post-treatment, 80% of the women remain alive, compared with a typical survival rate of 23.8% at 5 years for women with advanced breast cancer who receive conventional treatment. We intend to expand our evaluation of laser assisted immunotherapy with a second clinical study in 2013 in the Caribbean with a larger number of study subjects.
Laser-assisted immunotherapy’s positive findings have been presented at several major scientific conferences,16 and additional follow-up data is being prepared for publications.
Many cell lines can lurk in a single tumor, making cancer as individualized as a human fingerprint. For this reason, attempts to date to produce cancer vaccines have not been encouraging. Laser-assisted immunotherapy holds the promise of a non-toxic cancer intervention to eliminate primary tumors and to manufacture within each cancer patient’s body a personalized vaccine that can train the immune system to detect malignant cells wherever they lurk in the body and to eradicate them.
In Oklahoma City, the Life Extension Foundation funds a triple-negative (ER-, PR-, Her2Neu-negative) breast cancer cell line overseen by researcher Robert Nordquist, Ph.D. This cancer cell colony enables us to test a wide range of compounds to evaluate their efficacy alone, and in combination with other anti-cancer agents. One compound we have identified in this laboratory improved the cytotoxicity of a standard chemotherapy drug (Adriamycin) by 16 to 20 times. A lethal side effect of Adriamycin is cardiotoxicity that can kill the patient. By reducing the dose of Adriamycin needed, this new compound may enable Adriamycin to cure the cancer while sparing the patient’s heart. The efficacy of this novel combination therapy approach is being evaluated and clinical studies are being planned.
We have been testing a chemotherapy drug discovered by oncologist and Professor Don Richard Ishmael, M.D. Unlike conventional chemo drugs that work via one or two mechanisms, this compound interferes with cancer progression in several distinct ways. The significance of this discovery is that cancer cells develop their own survival pathways that circumvent the efficacy of chemo drugs. This is why conventional chemotherapy usually provides only a temporary benefit in those with clinically verified metastatic disease. By blocking cancer cell progression via distinct pathways that tumors use to escape eradication, this drug may provide the cancer patient with a greater chance of attaining a complete response or outright cure.
When tested on the breast cancer cell colony that we fund in Oklahoma City, Dr. Ishmael’s compound demonstrated greater cytotoxicity than any other compound the scientists have observed in more than 35 years. The synthetic protocol for the compound has been developed and has been tested in several animal models. We have been evaluating the optimal animal mode which we plan to complete in 2013. Upon successful completion of these studies the plan is to carry out primate studies in preparation for filing for an investigational new drug (IND) application to carry out Phase 1 human clinical studies.
The breast cancer cell colony in Oklahoma City has historical precedent in identifying better treatment methods. In 2001 and 2002, for example, poster presentations at prestigious cancer conferences revealed that separating the administration of the conventional chemo drugs gemcitabine and docetaxel greatly improved their cytotoxic effect against breast cancer cells. Move forward to year 2005 and a Phase I/II clinical study showed greater efficacy against a wide range of malignancies when alternating doses of these drugs were given (one week apart), i.e., the response rate was significantly improved compared to giving them together. In 2007, we committed to fund a Phase II clinical study to ascertain the efficacy of administering these two conventional chemo drugs (Gemzar® and Taxotere®) on an alternating week dosing schedule, despite no interest being expressed by pharmaceutical companies that owned the patents of these drugs. Surprisingly few patients have enrolled in this study, which is one reason why progress against horrific diseases like cancer has been so slow, i.e., recruiting patients for fully-funded clinical studies can be excruciatingly slow. Nevertheless, we are moving forward with the clinical evaluation.
The critical need to develop superior cancer imaging tools cleared a major hurdle in December 2012, when a U.S. pharmaceutical giant agreed to sell the shelved research and development rights to Combidex, a revolutionary magnetic resonance imaging (MRI) contrast agent. Combidex-enhanced scans can detect metastatic cancer lesions too small to be seen by traditional PET/CT imaging.17
Life Extension has been a strong advocate of Combidex since 2007, but bureaucratic red tape and an inadequately designed FDA application sidelined its approval, and the development of this cutting-edge diagnostic procedure seemed all but lost. As research collaborator, the International Strategic Cancer Alliance stayed the course and was able to negotiate the sale of the Combidex technology package to Radboud University Medical Center in the Netherlands. This year, world-renowned radiologist Jelle Barentsz, M.D., will begin the process of launching multi-country research trials, which will ultimately lead to new license applications, a commercialized product and widespread patient access.
While standard CT scans are unable to visualize a malignancy of less than 8 cm, Combidex allows for pinpoint detection of lymph node metastases as small as 4 mm.18 With an earlier and far more accurate diagnosis using this non-invasive procedure, positive nodes can be precisely treated with targeted radiation, or, in some cases, surgery.
Combidex (ferumoxtran-10) is composed of a simple sugar compound, dextran, and superparamagnetic iron oxide, or USPIO.19 These extremely small iron crystals (25-50 nanometers in diameter), become powerfully magnetized when exposed to the magnetic field of an MRI scanner. The injected Combidex contrast fluid is taken up selectively by the macrophages (scavenger cells) that are primarily found in lymph nodes and other inflammatory tissue.19,20
Dr. Barentsz is one of the few physicians in the world to have worked extensively with Combidex technology, predominantly in prostate cancer cases. In one study, Dr. Barentsz and his team compared traditional CT scans and Combidex-enhanced MRI lymphangiography (MRL) for 375 prostate cancer patients, 16% of whom had lymph node metastases. CT imaging detected only 34% of the positive nodes, while Combidex MRL identified a remarkable 82%. The diagnoses were microscopically confirmed by either a lymph-node dissection or a needle biopsy. The study group concluded that Combidex-enhanced MRL is 96% accurate, and can eliminate the need for highly invasive surgical lymph node dissections.21
Combidex scans have also been used to successfully evaluate patients with cancers of the uterus,22 head and neck,23 kidney, 24 breast,25 and liver.26
Life Extension is committed to pursuing emerging and novel technologies that have significant benefits at a reasonable cost to people who suffer from cancer. Our approach is very much focused on the best use of a healthy immune system to fight the disease, integrated with the most effective cancer therapies we can discover and clinically evaluate. With Life Extension Foundation funds, we have created an environment where researchers and clinicians can most efficiently explore new and promising treatment protocols. The cost of funding these research programs is significant, but we view the benefits to Life Extension members and the public at large as well worth the expenditure of our time and financial resources.
Enhanced PET Scan Reporting
The rapid expansion in the use of Positron Emission Tomography, or PET scans to obtain metabolic information about cancer lesions can provide oncologists and their patients with extremely valuable diagnostic and treatment management information.
PET scans use an injected radioactive tracer material like fluorodeoxyglucose (FDG) to produce functional imaging that can help differentiate benign from malignant masses, evaluate tumor stage, monitor response to therapy and detect tumor recurrence in a variety of malignancies.27 Coupled with the precise anatomical imagery produced by computerized tomography, FDG PET/CT can give rapid and accurate information about tumor size, location and rate of growth.
As useful as PET imaging can be, statistical errors can at times result in “false negative” or “false positive” reporting.28 Other issues that may trigger errors include improper PET scanner calibration with patient body weight, and the variability in FDG uptake depending on the elapsed time from when the radiotracer was injected into the patient. But the most egregious errors are perhaps due to incomplete or inconsistent scan interpretations caused by inadequate training and a lack of overall standards for the quantified reporting of results. Incorrect PET scans are common today and can result in improper treatments for cancer patients.
Working with radiologist Richard Black, M.D., the International Strategic Cancer Alliance adopted invaluable PET reporting practices in its Life Extension-supported laser-assisted immunotherapy breast cancer trial. Dr. Black has interpreted more than 70,000 PET/CT studies, and his methodology for an across-the-board upgrade in PET scan reporting should be incorporated at the national level to provide oncologists and their patients with the full potential PET technology has to offer. Dr. Black’s approach will assure that oncologists receive the same kind and quality of information on each and every scan, regardless of who interpreted the scan, or where it was taken. Here are the five key features of Dr. Black’s protocol:
- Quantitative Reporting : Standardized uptake values, or SUV readings are collected for every object of concern in the scan, not just narrative descriptions.
- Reproducible Reporting : SUV readings are standardized to an area of normal homogenous tissue in the liver to generate a corrected SUV for every area of concern. The correction factor allows different experts using different equipment to obtain similar results.
- Index Lesion Focus : “Hotspots” indicating tumor activity must be monitored from one study to the next to enable rapid and accurate measurements of changes over time or in response to therapy.
- Comparative Readings Mandate : PET scan reporting must make reference to the size, SUV, and other features of an index lesion(s) from previous scans, obligating the current radiologist to request those studies for a side-by-side comparison.
- Image Snapshots of Index Lesions : Allows the ordering physician to visualize the areas of abnormality, rather than relying solely on a written report.
Dr. Black presented his findings at one of LEF’s Scientific Advisory Board Meetings in 2012. His presentation can be viewed on the Life Extension website at the following URL: www.lef.org/PET-CT
Ursolic acid is a chemical found in plants that is known to have anti-cancer, antioxidant, and anti-inflammatory effects. The Life Extension Foundation has been funding a clinical trial on ten subjects to assess the absorption, distribution, metabolism, and excretion of varying doses of ursolic acid. Ursolic acid has been used in cosmetic and health products, and is non-toxic.29
America’s obesity epidemic is unparalleled in modern times and comparable only to smoking in terms of the collateral disease it generates.30 Diabetes, hypertension, heart disease, stroke and cancer are among obesity’s many co-morbidities,31 creating a public health challenge of massive proportions.
A Life Extension-supported multi-year review of 9,088 patients in a private practice clinic documented that the obesity crisis is far more widespread 32 than the current national estimate of slightly more than one in three Americans suggests.33 Published in the April 2012 issue of the scientific journal PLoS One, our study found that 39% of the patients classified as non-obese, were, in fact, obese, when body fat percentages were taken into account.
This huge discrepancy was caused by the failure of the routinely used body mass index (BMI) to measure adiposity accurately. The 200-year-old BMI measurement is a simple calculation of weight (kg) divided by height (m) squared. Study co-authors Nirav Shah, M.D., who is now the New York State Commissioner of Health, and Eric Braverman, M.D., of Weill Cornell Medical College and the longevity research non-profit the PATH Foundation, analyzed the charts of 1,393 of the patients for whom both BMI and direct body fat percentages were available. Dual-energy X-ray absorptiometry scans provided precise body adiposity measurements. Based on BMI scores alone, only 26% of the study participants were classified as obese. When the DXA body fat scans were utilized, an astounding 64% were found to be obese. The findings from this study made headline news stories around the world.
By gender, BMI measurements produced false-negative results for 25% of men and 48% of women. The scores were particularly misleading for women over the age of 50, who lose far more muscle mass as they age than men. As women advance in years, this misclassification increases, with 59% of women misclassified as non-obese by age 70+.
Aging women are also far more likely to have higher levels of leptin, a 16 kDa peptide secreted by adipocyte cells to regulate the body’s energy balance by decreasing food intake and increasing energy expenditure. Leptin insensitivity and high leptin levels are associated with chronic inflammation, type 2 diabetes, hypertension and myocardial injury.32
The National Institutes of Health (NIH) currently classifies a BMI score of 25 to 29.9 as overweight and a BMI of 30 or above as obese.34 The study’s authors propose revised BMI cut-off points of 24 for women and 28 for men, along with a blood test for leptin levels and DXA scanning, when available, to obtain a more precise diagnosis of obesity, and improved clinical management of the disease.
More than 5 million Americans are stricken with Alzheimer’s disease today. One out of three Americans over age 85 is diagnosed with Alzheimer’s. As the aging population increases, the prevalence will approach 13 to 16 million cases in the United States by 2050.
A startling discovery revealed that an FDA-approved autoimmune disease drug (Enbrel®) may reverse the clinical course of Alzheimer’s disease by blocking a pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a) that damages the brain. Alzheimer’s patients who had this drug perispinal extrathecal-administered in the posterior neck, delivering Enbrel® to the brain via the cerebrospinal venous system, experienced remarkable cognitive improvements in minutes.35 Data published in 2011 also showed the benefit of perispinal Enbrel® in restoring cognitive function in three consecutive patients with stable and persistent chronic neurological deficits due to strokes that had failed to resolve despite previous treatment and rehabilitation. The onset of clinical response was evident within 10 minutes of perispinal injection in all patients, including improvements in hemiparesis, gait, hand function, hemi-sensory deficits, spatial perception, speech, cognition and behavior.36
Enbrel® is an expensive drug and administering it in a way that delivers it to the brain is an intricate medical process. The Life Extension Foundation has been sponsoring a study being conducted in Florida for individuals diagnosed with mild to moderate Alzheimer’s disease. The objective of the research initiative is to measure the effects of weekly Enbrel® injections plus nutritional supplements that may suppress the inflammatory factor implicated in the neuronal degeneration of Alzheimer’s disease.
As of January 2013 six subjects have completed the study, but the study is continuing to recruit. To participate in this study register now online at www.lef.org/clinicalresearch or send an e-mail expressing your interest in participating in this study to: LEClinicalResearch@LifeExtension.com. For any further information you may call the Life Extension Clinical Research Department at (866) 517-4536 between 9:00 a.m. and 5:00 p.m. ET or leave a voicemail after hours with your name and contact information.
21st Century Medicine (21CM) is largely funded by Life Extension Foundation. 21CM’s mission is to develop methods for reversibly cryopreserving complex systems, particularly systems too complex for anyone else to cryopreserve.
21CM has been successful with cartilage, corneas, and organ slices including brain, kidney, and, most recently, liver. Cartilage banking could help people suffering from degenerative joint conditions or sports injuries. Cornea banks should help patients with corneal blindness. Organ slice banking could help the pharmaceutical industry develop new drugs for treating any number of diseases affecting the brain, kidneys, and livers.
Organ slice banking is desirable because many drugs are metabolized to toxic byproducts in the liver even if they are intended for the treatment of a site that otherwise has nothing to do with the liver. So organs that metabolize drugs, such as livers, kidneys, intestines, and lungs, have more general relevance for the drug discovery and development process, thus making the successful banking of such organ slices a major advance.
The biggest payoff for organ slice banking for drug development purposes will come from the ability banking will create for drug companies to have access to human tissue. Right now, for example, with only a few hours of viability after collecting a liver from a human cadaver, it’s effectively impossible for most livers (either basically good ones or diseased ones) to get processed into slices by drug companies before they become useless, but with banking, regional centers could rapidly reduce the organs to massive numbers of slices that could be utilized years or decades later, by large numbers of users including not only drug companies but also universities interested in human biology.
21CM also has an ongoing program for banking whole kidneys, the only such program in the world as far as they know. 21CM has shown that the goal can be achieved, because they once vitrified a kidney, transplanted it, and had it support the recipient’s life indefinitely, but the method is currently being refined to make it more perfect. Banks of major transplantable organs would reduce waste caused by logistic problems and by the current short storage times for most organs, would potentially allow for immune-engineering methods to be applied that would enable all allografts to be accepted without rejection and without long term immunosuppression. When laboratory mass production of organs becomes possible so as to meet the shortfall between supply and demand, organ banking would enable these newly available organs to be distributed safely and without constraints, much the way that blood is preserved until it is needed. These generic organs could be distributed to local hospitals and kept there in banks, where they could be used under emergency conditions, saving accident, poisoning, or assault victims who otherwise could have perished from acute organ failure. This could have applications for the treatment of wounded soldiers as well.
21CM also has a brain program. Its two aims are 1) to be able to bank brains well enough to establish an excellent case for revival, or even to be able to bank brains with demonstrable recovery of viability, and 2) to be able to preserve brains by more conventional means long enough for them to be cryopreserved under good conditions. The second goal could enable critically injured people to be shipped cross-continentally for emergency surgeries or other repairs that are not possible locally, and there may be applications for the protection of wounded soldiers, who might be cooled and stabilized in mobile units and then transported to aircraft carriers for repair and resuscitation. This is complementary to the Critical Care Research (another company funded by LEF) work, and LEF can justify the stabilize-ship-and-repair scenario that might emerge from brain cold storage research because of the foundation CCR has created and continues to refine. 21CM’s work on brain models here suggests that the brain is the weak link in the chain, so that when 21CM can take care of that link, CCR may be able to apply it successfully to demonstrate longer reversible preservation.
Rejuvenation of Old Worms
Dr. Cynthia Kenyon is a Distinguished Professor of Biochemistry and Biophysics at the University of California who achieved world fame in 1993 when she doubled the life span of nematode worms by means of a single mutation. Recently she has discovered indications that certain worm mutations under some conditions will allow worms to become younger. In mid-2012 LEF made a grant to Dr. Kenyon to investigate these mechanisms with the hope of rejuvenating old worms. If this works, it could potentially make old people young again.
Funding a Former Ellison Foundation Scholar
Every year, the Ellison Foundation awards four-year grants to some of the most promising and productive aging researchers in the world. At the end of their four-year grants, these researchers must look elsewhere for funds if they wish to continue their work. In January 2013, the Life Extension Foundation began funding former Ellison Foundation New Scholar Dr. Victoria Belancio to continue her work on the molecular biology of transposable DNA elements (“jumping genes”). She will be studying different levels of light at night in rats. By learning how disturbances in circadian rhythm (such as is experienced by shift workers and world travelers) lead to genetic instability, cancer, and aging, Dr. Belancio hopes to demonstrate how intervention can mitigate the negative effects.
Clinical Trials of Depression Therapies
Early in 2013, Dr. Matthew Bambling at the Department of Psychiatry of the University of Queensland in Australia began recruiting patients for a Life Extension Foundation-supported clinical trial. Dr. Bambling was impressed by the report of the effects of a 6-week study described in the December 2010 issue of Life Extension Magazine®37 in which SAMe (S-Adenosyl Methionine) produces anti-depressive benefits for patients who have not responded to conventional anti-depression therapy using serotonin-reuptake inhibitors. Dr. Bambling and his colleague will extend the study cited in Life Extension Magazine to 15 weeks using twice the dose of SAMe, and more carefully assess symptom improvement and relapse effects.
The Life Extension Foundation has been funding another study on depression — a double-blind randomized clinical trial at the University of Miami using magnesium sulfate. Low blood levels of magnesium38 and low levels of dietary magnesium intake37 have been observed in patients suffering from depression. Mouse studies support the view that magnesium is critical for synthesis of depression-related neurotransmitters in the brain, 40,41 so clinical trials on human subjects seem justified.
Clinical Trials with Cognitive Enhancing Nutrients
Life Extension has an in-house Clinical Research Department that has conducted numerous clinical trials, including the Alzheimer’s disease study with Etanercept mentioned above. The Clinical Research Department has also conducted a clinical trial assessing the effects of supplementation with a multi-nutrient formula called Cognitex® on subjects displaying subjective memory complaints. Study results were presented on April 24 at the 2012 Experimental Biology Conference in San Diego, authored by three of Life Extension’s staff physicians: Dr. Steven Hirsh, Dr. Peter Zhang, and Dr. Steven Joyal. Statistically significant improvement was obtained in several tests of cognitive function after 60 days of supplementation with Cognitex ®.
Spearheading the Search for Authentic Anti-Aging Therapies
Finding better treatments for cancer, Alzheimer’s disease and other ailments is one part of Life Extension’s larger goal of developing therapies that will enable humans to gain control over aging.
The discovery of authentic anti-aging therapies will preempt or postpone the diseases of aging, in addition to extending the length of the human life span.
The commitment of Life Extension Foundation to achieve these goals has been unwavering; despite relentless attacks by government bureaucrats who believe that pathological aging and death are natural events that should not be interfered with.
- Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003 Jan 8;289(2):179-86.
- Available at: http://www.cancer.org/research/cancerfactsfigures/cancerfactsfigures/cancer-facts-figures-2012 Accessed January 12, 2013
- Bonnet S, Archer SL, Allalunis-Turner J, et al. A mitochondria-K+ channel is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 2007 Jan;11(1):37-51.
- Felitsyn N, Stacpoole PW, Notterpek L. Dichloroacetate causes reversible demyelination in vitro: potential mechanism for its neuropathic effect. J Neurochem. 100:429-436, 2007.
- Wong JY, Huggins GS, Debidda M, et al. Dichloracetate induces apoptosis in endometrial cancer cells. Gynecol Oncol. 2008;109:394-402.
- Michelakis ED , Sutendra G, Dromparis P, et al. Metabolic modulation of glioblastoma with dichloracetate. Sci Transl Med. 2010 May 12;2(31)ra34.
- Strum SB, Adalsteinsson O, Black RR, et al. Case Report: Sodium Dichloracetate (DCA) inhibition of the “Warburg Effect” in a human cancer patient: complete response in non-Hodgkin’s lymphoma after disease progression with rituximab-CHOP. J Bioenerg Biomembr. 2012 Dec 20 (Epub ahead of print).
- Strum SB, Adalsteinsson O, Black RR, et al. J Bioenerg Biomembr. 2012 Dec 20. [Epub ahead of print]
- Yamamoto N, Suyama H, Yamamoto N, Ushijima N. Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF). Int J Cancer. 2008 Jan 15;122(2):461-7.
- Yamamoto N, Suyama H, Yamamoto N. Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF. Trans Oncol. 2008 Jul;1(2):65-72.
- Yamamoto N, Suyama H, Nakazato H, Yamamoto N, Koga Y. Immunotherapy of metastatic colorectal cancer with vitamin D-binding-protein-derivedd macrophage-activating factor, GcMAF. Cancer Immunol Immunother. 2008 Jul;57(7):1007-16.
- Mohamad SB, Nagasawa H, Uto Y, Hori H. Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation. Comp Biochem Physiol A Mol Integr Physiol. 2002 May;132(1):1-8.
- Sanders AM, Stehle JR Jr, Blanks MJ, et al. Cancer resistance of SR/CR mice in the genetic knockout backgrounds of leukocyte effector mechanisms: determinations for functional requirements. BMC Cancer. 2010 Mar 31;10;121.
- Riedlinger G, Adams J, Stehle JR Jr., et. al. The spectrum of resistance in SR/CR mice: the critical role of chemoattraction in the cancer/leukocyte interaction. BMC Cancer. 2010 May 3;10:179.
- Available at: http://www.clinicaltrials.gov/ct2/show/record/NCT00900497?term=maharaj+granulocytes&rank = Accessed January 25, 2013.
- Li X, Ferrel GL, Guerra MC, et al. Preliminary efficacy and safety results of laser assisted immunotherapy for the treatment of metastatic breast cancer patients. Photochem Photobiol Sci. 2011 May;10(5):817-21.
- Harisinghani MG, Barentsz J, Hahn P, et al. Noninvasive Detection of Clinically Occult Lymph-Node Metastases in Prostate Cancer. N Engl J Med. 2003 Jun;348:2491-2499.
- Deserno WM, Harisinghani MG, Taupitz M, et al. Urinary bladder cancer: preoperative nodal staging with ferumoxtran-10- enhanced MR imaging. Radiology. 2004 Nov;233(2):449-56.
- Barentsz JO, Futterer JJ, Takahashi S. Use of ultrasmall superparamagnetic iron oxide in lymph node MR imaging in prostate cancer patients. Eur J Radiol. 2007 Sep;63(3):369-72.
- Corot C, Robert P, Idée JM, Port M. Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliv Rev. 2006 Dec 1;58(14):1471-504.
- Heesakkers RA, Hovels AM, et al. MRI with a lymph-node-specific contrast agent as an alternatie to CT scan and lymph-node dissection in patients with prostate cancer: a prospective multicohort study. Lancet Oncol. 2001 Sep;9(9):850-6.
- Laghi A, Paolantonio P, Panebianco V, et al. Decrease of signal intensity of myometrium and cervical stroma after ultrasmall superparamagnetic iron oxide (USPIO) particles administration: an MR finding with potential benefits in T staging of uterine neoplasms. Invest Radiol. 2004 Nov;39(11):66670.
- Curvo-Semedo L, Diniz M, Miguéis J, et al. USPIO-enhanced magnetic resonance imaging for nodal staging in patients with head and neck cancer. J Magn Reson Imaging. 2006 Jul;24(1):123-31.
- Guimaraes AR, Tabatabei S, Dahl D, et al. Pilot study evaluating use of lymphotrophic nanoparticleenhanced magnetic resonance imaging for assessing lymph nodes in renal cell cancer. Urology. 2008 Apr;71(4):70812.
- DaldrupLink HE, Rydland J, Helbich TH, et al. Quantification of breast tumor microvascular permeability with feruglose enhanced MR imaging: initial phase II multicenter trial. Radiology. 2003 Dec;229(3):88592.
- Yoo HJ, Lee JM, Lee MW, et al. Hepatocellular carcinoma in cirrhotic liver: doublecontrastenhanced, highresolution 3.0T MR imaging with pathologic correlation. Invest Radiol. 2008 Jul;43(7):53846.
- Yoon KT, Kim JK, Kim do Y, et al. Role of 18F-flourodeoxyglucose positron emission tomography in detecting extrahepatic metatastasis in pretreatment staging of hepatocellular carcinoma. Oncology. 2007;72 Suppl 1:104-10.
- Black RR. Optimization of FDG PET-CT imaging in oncology 2012 (Power point presentation).
- Liu J. Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol. 1995 Dec 1;49(2):57-68.
- Jia H, Lubetkin EI. Trends in quality-adjusted life-years lost contributed by smoking and obesity. Am J Prev Med. 2010 Feb;38(2):138-44.
- Malnick SD, Knobler H. The medical complications of obesity. QJM. 2006 Sep;99(9):565-79.
- Shah NR, Braverman ER. Measuring adiposity in patients: the utility of body mass index (BMI), percent body fat, and leptin. PLoS One. 2012;7(4):e33308.
- Berrington de Gonzalez A, Hartge P, Cerhan JR, Flint AJ, Hannan L, MacInnis RJ, Moore SC, Tobias GS, Anton-Culver H, Freeman LB, Beeson WL, Clipp SL, English DR, Folsom AR, Freedman DM, Giles G, Hakansson N, Henderson KD, Hoffman-Bolton J, Hoppin JA, Koenig KL, Lee IM, Linet MS, Park Y, Pocobelli G, Schatzkin A, Sesso HD, Weiderpass E, Willcox BJ, Wolk A, Zeleniuch-Jacquotte A, Willett WC, Thun MJ. Body-mass index and mortality among 1.46 million white adults. N Engl J Med. 2010 Dec 2;363(23):2211-9.
- Tobinick E. Tumour necrosis factor modulation for treatment of Alzheimer’s disease: rationale and current evidence. CNS Drugs. 2009 Sep 1;23(9):713-25.
- Tobinick E. Rapid Improvement of Chronic Stroke Deficits after Perispinal Etanercept: Three Consecutive Cases. CNS Drugs. 2011 Feb. 1;(25):145-155.
- Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry. 2010 Aug;167(8):942-8.
- Barragan-Rodríguez L, Rodríguez-Morán M, Guerrero-Romero F. Depressive symptoms and hypomagnesemia in older diabetic subjects. Arch Med Res. 2007 Oct;38(7):752-6.
- Jacka FN, Overland S, Stewart R, Tell GS, Bjelland I, Mykletun A. Association between magnesium intake and depression and anxiety in community-dwelling adults: the Hordaland Health Study. Aust N Z J Psychiatry. 2009 Jan;43(1):45-52.
- Kantak KM. Magnesium deficiency alters aggressive behavior and catecholamine function. Behav Neurosci. 1988 Apr;102(2):304-11.
- Cardoso CC, Lobato KR, Binfaré RW, Ferreira PK, Rosa AO, Santos AR, Rodrigues AL. Evidence for the involvement of the monoaminergic system in the antidepressant-like effect of magnesium. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Mar 17;33(2):235-42.