In The News: October 2016

Internet search giant Google established Calico in 2013 as an independent research and development biotech company, but little information about the endeavor has been forthcoming. Calico’s new website sheds some light on their general plans in the field of anti-aging research.*

Calico’s site says their mission is to “harness advanced technologies” to increase scientific understanding of how biology controls lifespan. They say they will “use that knowledge to devise interventions that enable people to lead longer and healthier lives,” and they believe this will require “an unprecedented level of interdisciplinary effort and a long-term focus for which funding is already in place.”

Although details remain scarce, it’s also been announced that Cynthia Kenyon, an oncology professor from the University of California, San Francisco, has been promoted to vice president of aging research. Given Google’s very deep pockets, their potential for making major contributions to the anti-aging field seems promising.

Editor’s Note: Calico says their vice president of business development, Jonathan Lewis, will be in charge of supporting “the company’s growth through partnerships and collaborations,” which would seem to indicate an encouraging willingness to work with other biotech companies.

Mark Zuckerberg, the CEO and founder of Facebook, has announced a wildly ambitious proposal to fund medical research with an eye toward finding cures for and methods to prevent major diseases.*

The plan is part of the Internet giant’s Chan-Zuckerberg Initiative, which he established with his pediatrician wife, Priscilla Chan.

In a statement to investors, Zuckerberg said, “While helping to connect the world will always be the most important thing that I do, there are more global challenges that I also feel a responsibility to help solve...Things like helping to cure all disease by the end of the century.”

In his original announcement trumpeting the creation of the initiative, Zuckerberg expressed dismay at the fact that, according to him, 50 times more money is spent on medical treatments than on medical research. His response is a pledge to contribute 99% of his Facebook shares within his lifetime to a wide range of causes including medical advancement.

“We have a real shot at preventing, curing or managing (most or all diseases) in the next 100 years,” Zuckerberg said.

Editor’s Note: “Today, most people die from five things,” Mark Zuckerberg has stated, “heart disease, cancer, stroke, neurodegenerative and infectious diseases. And we can make faster progress on these and other problems.”

In the journal Hepatology, Mayo Clinic researchers reported findings from a study that compared 2,395 bile duct cancer patients with 4,769 controls matched for age and other factors.* Jonggi Choi, MD, and colleagues calculated a 2.7-fold to 3.6-fold lower risk of bile duct cancer (cholangiocarcinoma) among aspirin users compared with the risk for nonusers. Aspirin users had a 65% lower risk of intrahepatic bile duct cancer, a 66% lower risk of perihilar bile duct cancer and a 71% lower risk of distal disease. It was also shown that the presence of cirrhosis and other factors affected the risk of the three subtypes in different ways.

“Until now, there has been little evidence of a potential role for aspirin in the prevention of bile duct cancer,” noted coauthor Roongruedee Chaiteerakij, MD, PhD. “Our study provides the first evidence for this.”

Bile duct cancer is a particularly lethal malignancy.

Editor’s Note: “Chronic persistent inflammation is one of the key elements that promote cancer of the bile ducts, and well-known risk factors for bile duct cancer have all been shown to increase the risk for bile duct cancer by inducing chronic inflammation of the ducts,” Dr. Choi observed. “Aspirin is an anti-inflammatory agent and may reduce the risk of bile duct cancer by reducing inflammation through inhibition of the cyclooxygenase enzyme. Previous studies have shown that aspirin also blocks additional biological pathways that promote cancer development.”

A meta-analysis that included a total of over 1.4 million subjects found a lower risk of dying from cardiovascular disease in patients using metformin compared to those treated with another class of diabetes drugs known as sulfonylureas.*

Researchers analyzed data from 204 studies (179 trials and 25 observational studies) that included men and women treated with metformin, sulfonylureas and other drugs. The investigators examined cardiovascular and other effects associated with the different therapies.

Metformin as well as sulfonylureas were found to be more effective at reducing blood glucose levels than DPP-4 inhibitors. Another type of drug known as SGLT-2 inhibitors was associated with fungal infections in 10% of users, however, the drugs supported patients’ weight loss efforts. In contrast, sulfonylurea drugs were associated with weight gain. Compared with the use of sulfonylureas, metformin was associated with a 30% to 40% lower risk of dying from cardiovascular disease.

Editor’s Note: “Metformin looks like a clear winner,” announced co-primary investigator Nisa Maruthur, MD, MHS, who is an assistant professor of medicine at Johns Hopkins University School of Medicine. “This is likely the biggest bit of evidence to guide treatment of type II diabetes for the next two to three years.”

The Hellenic Journal of Nuclear Medicine reported finding an association between low serum vitamin D levels and a marker of the autoimmune disease known as Hashimoto’s thyroiditis.*

The study included 218 Hashimoto’s thyroiditis patients with normal thyroid-stimulating hormone levels. Subjects in the study lived on Crete, an island in Greece that provides the abundant sunlight needed for vitamin D formation. Blood tests measured serum 25-hydroxyvitamin D and other values. Hashimoto’s thyroiditis diagnosis was determined by elevated levels of the antibodies antithyroid peroxidase and/or antithyroglobulin, as well as ultrasound results.

Deficient serum vitamin D levels of less than 30 ng/mL were detected in 85.3% of the participants. Among deficient subjects, antithyroid peroxidase levels were significantly higher than levels measured in the sufficient group. However, supplementation with 1,200 to 4,000 IU vitamin D3 daily by the deficient group for four months resulted in a 20.3% decrease in anti-thyroid peroxidase antibody by the end of the study.

Editor’s Note: In Hashimoto’s thyroiditis, the thyroid gland is attacked by the immune system, which can lead to hypothyroidism. The condition is the most common cause of hypothyroidism in the US.

Researchers from Roswell Park Cancer Institute and SWOG presented findings at the American Association for Cancer Research meeting, which found that regularly taking a multivitamin prior to breast cancer diagnosis may reduce the risk of chemotherapy-induced peripheral neuropathy in patients treated with taxane-based chemotherapy drugs.*

Gary Zirpoli, PhD, and colleagues analyzed data collected from 1,125 breast cancer patients enrolled in a National Cancer Institute group trial to determine whether use of dietary supplements was related to the presence of chemotherapy-induced peripheral neuropathy.

The use of individual supplements didn’t appear to offer any help. However, patients who regularly took a multivitamin prior to diagnosis were significantly less likely to experience symptoms than those who did not.

Editor’s Note: “Because development of chemotherapy-induced neuropathy is difficult to predict and symptoms can remain long after treatment has concluded, identifying preventive measures has the potential to greatly enhance quality of life for a substantial number of breast cancer survivors,” says Dr. Zirpoli.

Considerable evidence links both vitamin D and metformin to reduced cancer risk as well as better patient outcomes.^1-6 Now, emerging research suggests that in combination, these two safe and well-studied compounds may be even more effective against cancer than either alone.⁷

In 2015, Dr. Hong-Xia Li and colleagues from Lanzhou University in China published compelling evidence of a synergistic growth-inhibitory effect of metformin and vitamin D on prostate cancer cells.⁷

Metformin is thought to exert anticancer effects through several pathways. One of these is by suppressing cancer cell proliferation via increased phosphorylation of AMPK and subsequent inhibition of the mTOR/S6K pathway, which influences protein synthesis and cell growth.^7,8

Metformin also appears to downregulate the expression of some matrix metalloproteinases,⁹ enzymes that can contribute to cancer growth and spread.^10,11 (Interestingly, recent studies suggest that vitamin E, particularly its gamma-tocotrienol form, can also downregulate expression of certain matrix metalloproteinases, raising the possibility that metformin and vitamin E may provide additive or complementary benefits in cancer.^12,13)

Vitamin D promotes healthy cell differentiation, a process by which immature cells develop into specific types of cells with specialized functions. Tumors containing poorly differentiated cancer cells tend to be more aggressive than those with well-differentiated cells.^14,15

Dr. Li and his team observed that incubating androgen-insensitive prostate cancer cells with metformin reduced their growth by 28% while vitamin D3 slowed the cancer cells’ growth by nearly 45%. But when the prostate cancer cells were incubated with a combination of metformin and vitamin D3, growth inhibition reached an impressive 86%.⁷

This research followed up on similar findings from an earlier study by this same laboratory. In the earlier study, mice and rats were given colon cancer-promoting chemicals, and combined treatment with metformin and vitamin D3 suppressed the development of precancerous lesions and tumors more effectively than either compound alone.¹⁶

Other scientists have observed similar synergistic effects of vitamin D3 and metformin in bladder and breast cancer cells.^17,18

This mounting evidence suggests combined metformin and vitamin D3, both of which have an established safety record,^19-22 could represent a powerful tool in the fight against cancer. By undermining cancer cell viability by different mechanisms, metformin together with vitamin D3 fulfills a key criterion of conventional chemotherapeutic drug combinations.⁷ Additionally, research indicates that certain forms of vitamin E may have anticancer properties complementary to those of vitamin D and metformin.^12-13,23

The German Internet mogul Michael Greve has announced his intention to contribute $5 million over the next five years via his Forever Healthy Foundation to Aubrey de Grey’s SENS Research Foundation (SENS).*

SENS is a nonprofit group dedicated to promoting new approaches to the way medical science traditionally researches and treats age-related disease. Additionally, Greve’s company KIZOO Technology Ventures will commit $5 million to seed investments for startups that aim to bring rejuvenation biotechnology treatments to market.

Greve said, “I think we should have more people contribute to the step-by-step creation of cures for the root causes of all age-related diseases. And we should have a whole rejuvenation industry based on the SENS treatment model including the self-accelerating feedback-loop of success stories and amazing opportunities for scientists, entrepreneurs, and VC investors. This will truly accelerate both research and therapies. I have decided to lead by example and make this $10 million commitment.”

Editor’s Note: The initial donation from the Forever Healthy Foundation will benefit such projects as the study of pharmacological and/or enzymatic cleavage of glucosepane crosslinks led by Dr. David Spiegel at Yale University, as well as allotopic expression of mitochondrial genes led by Dr. Matthew O’Connor at the SENS Research Foundation, and the SENS Research Foundation’s Education Program led by Greg Chin.

In a study announced at the American Society of Clinical Oncology annual meeting on June 5, 2016,¹ the recently approved drug Darzalex™ demonstrated substantial efficacy in improving survival rates in end-stage multiple myeloma patients.^2-4

Darzalex™ was incorporated as a part of a multiple drug combination therapy for those whose cancer had responded poorly to existing treatments. The newly tested protocol adds Darzalex™ into the currently existing practice of a two-drug combination therapy of the proteasome-inhibitor bortezomib and the side-effect counteractant dexamethasone.

In the 498-patient study, subjects whose multiple myeloma had not formerly responded to a median of two standard therapies were enrolled. Treatment consisted of Darzalex™ in a three-drug combination group, with the control group being the standard two-drug combination protocol. Patients treated with the three-drug combination that included Darzalex™ showed a 61% decrease in the incidence of disease progression or death over the control group after a median follow up of 7.4 months.⁴

Additionally, the proportion of patients with a reduction in malignancies was markedly higher in the group that incorporated Darzalex™ into its treatment regimen. The Darzalex™ group showed an overall response rate of 83% while the control group demonstrated a 63% overall response rate.⁴

Despite the documented effectiveness of the drug in combination therapy, the costliness of the regimen appears to make it unattainable to most as a first-line treatment. The price to undergo the first years’ therapy using the three-drug protocol is $180,000, and insurance companies may refuse to pay for this because they can claim it’s still “experimental.”⁵

—By Chase Falcon

A new study has found another mechanism that may account for reported negative health effects of over-the-counter heartburn drugs.*

Studies have linked longtime use of these types of medications, known as proton pump inhibitors, with such maladies as dementia, heart disease, and kidney disease. This research established correlation without identifying a possible cause. But now, a study led by Dr. John P. Cooke at Houston Methodist Research Institute, Texas, has found that prolonged use of proton pump inhibitors may lead to premature aging of the endothelial cells that line the interior of blood vessels. Results also showed that proton pump inhibitors interfere with the ability of lysosomes—organelles that take out the body’s biological trash—to do their job, which also contributes to premature cell aging.

Editor’s Note: Says Dr. John P. Cooke, “Unless otherwise indicated, physicians should consider proton pump inhibitors only for short-term use for relief of symptoms of GERD.”