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 article, 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 article is to enlighten people about the research programs we are funding and detail LEF’s commitment to meaningful scientific discovery.
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 the State University of New York – Upstate Medical University 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 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.