Keeping one step ahead of cancer cells

Date:September 15, 2015

Source:Research Institute of Molecular Pathology

Summary: BRD4 inhibitors are among the most promising new agents in cancer therapy that are currently evaluated in clinical trials. In a new study, a team of researchers reveals how leukemia cells can evade the deadly effects of BRD4 inhibition. Understanding this adaptation process could aid the development of sequential therapies to outsmart resistant leukemias.

BRD4 inhibitors are among the most promising new agents in cancer therapy that are currently evaluated in clinical trials. In a study published in NATURE, a team of researchers at the Research Institute of Molecular Pathology (IMP) and Boehringer Ingelheim in Vienna reveals how leukemia cells can evade the deadly effects of BRD4 inhibition. Understanding this adaptation process could aid the development of sequential therapies to outsmart resistant leukemias.

Over the past years, scientists have drawn an almost complete map of mutations in cancer. However, translating complex genetic knowledge into effective cancer therapies turns out to be a major challenge for modern medicine. Searching for new ways to attack cancer cells, the laboratory of Johannes Zuber at the IMP in Vienna uses so-called functional genetic screens to probe vulnerabilities of cancer cells in a systematic and unbiased way. The major goal is to find genes that cancer cells particularly depend on, and then exploit these “Achilles’ heels” for the development of targeted therapies. In a first study applying this technology, Zuber and his former colleagues at Cold Spring Harbor Laboratory (New York) in 2011 found that the gene BRD4 is such an “Achilles’ heel” in acute myeloid leukemia (AML), an aggressive form of blood cancer. This discovery sparked a lot of excitement about BRD4 as a new target for leukemia therapy, and only four years later several BRD4 inhibitors have entered clinical trials, some of which have already reported promising results.

Resistance to new cancer therapies is often poorly understood

Despite this rapid advance, doctors and researchers still do not understand why some cancers are so sensitive to BRD4 inhibitors while others remain resistant. “After discovering a new Achilles’ heel, we often have no clue why cancer cells depend on a certain gene, although this knowledge would be crucial for developing targeted therapies and selecting the right patients,” explains Zuber. In the case of BRD4, finding an answer to this question turned out to be particularly challenging. To tackle this problem, Zuber and his group at the IMP teamed up with previous co-workers in the U.S. and scientists at Boehringer Ingelheim in Vienna led by Norbert Kraut to characterize sensitive and resistant cancer cells. Results from this work have been published in Nature and reveal a fascinating new mechanism how leukemia cells evade their dependency on BRD4.

As a known regulator of transcription, BRD4 controls the activity of hundreds of genes, which are simultaneously turned off after inhibitor treatment. In leukemia, one particularly important gene controlled by BRD4 is the MYC oncogene, which leukemia cells need for their indefinite growth. Treatment with BRD4 inhibitors shuts off this important cancer gene, and leukemia cells either die or develop into normal blood cells. To better understand why only certain leukemia subtypes are sensitive to BRD4 inhibition, Zuber and his colleagues first performed a genetic screen and found that loss of the so called PRC2 complex, which is known to inactivate genes during normal development, can render leukemia cells resistant to BRD4 inhibitors. By further characterizing these cells they found out that MYC and other BRD4-regulated genes were back on again, so leukemia cells had found a way to activate these genes in the absence of BRD4.

Cancer cells “learn” to evade the effects of BRD4 inhibitors

When the researchers then compared cells that had acquired resistance during drug treatment to leukemia cells that were resistant in the first place, they found that in both cases leukemia cells use very similar pathways to turn critical genes such as MYC back on and thereby escape the deadly effects of BRD4 inhibition. “It looked as if sensitive leukemia cells just learned what resistant cells already knew,” explains postdoctoral scientist Philipp Rathert, who spearheaded the study together with Mareike Roth, a graduate student in the Zuber laboratory. One particularly important pathway turned out to be WNT signalling, which is known to activate MYC in colon cancer and other cancer subtypes.

To look at the regulation of MYC in even more detail, Zuber was able to take advantage of close interactions with Alexander Stark at the IMP, whose laboratory has recently developed a method called “STARR-seq.” This technology has revolutionised the study of so-called enhancers, which are DNA regions involved in gene regulation. Using this new method, the team found that resistant leukemia cells activate MYC through a very small enhancer region that is bound by WNT components and gains activity following BRD4 inhibition.

A new biomarker to predict success of leukemia therapy

To explore whether this detailed knowledge could be used to predict which patients respond to BRD4 inhibitors, the team harnessed a long-standing collaboration with the group of Peter Valent at the Medical University of Vienna. When measuring WNT signalling markers, the team found that patient cells with low WNT activity were sensitive to BRD4 inhibitors, while high WNT activity was associated with resistance. This means the researchers may hold in hands a first “biomarker” for predicting the success of BRD4 inhibitor therapy.

Collectively, the study reveals that leukemia cells can become resistant to BRD4 inhibitors by rewiring the regulation of critical BRD4 target genes. This “transcriptional plasticity” highlights an emerging mode of drug resistance that is distinct from established resistance mechanisms such as mutations in binding pockets or drug elimination through efflux pumps. While this showcases once more that cancer cells can adapt to targeted therapies, Zuber and his colleagues at the IMP and Boehringer Ingelheim believe that a better understanding of these adaptation mechanisms will lead to combination therapies that will ultimately outsmart cancer cells: “We now have learned that cancer cells can adapt to targeted therapies, but their repertoire of escape routes is quite limited,” comments Zuber on the implications of their study. “A better understanding of the common escape routes will allow us to predict the next effective targeted therapy, so that we are always one step ahead of the cancer cell.”

---

Story Source:

The above post is reprinted from materials provided by Research Institute of Molecular Pathology. Note: Materials may be edited for content and length.

Read More

Researchers taking bold steps toward engineering new lungs

According to the World Health Organization, chronic obstructive pulmonary disease (COPD) currently affects more than 64 million people worldwide and is poised to become the third leading cause of mortality by 2030.

A hallmark of COPD is scarring of the lungs, a condition called pulmonary fibrosis, which impacts breathing. There is no cure for the condition or ability to repair the scarring that has occurred. Thus, in the late stages of lung disease, one remedy exists: organ transplantation.

Unfortunately, the combination of a severe shortage of donor organs and frequent rejection of the transplant by the recipient’s immune system has made even this method of last resort impractical for many.

In new research by Cheryl Nickerson and her team at Arizona State University’s Biodesign Institute and external collaborators, a radical approach to addressing the problems of transplantation potential and repairing scarred lungs is under investigation.

In work appearing in the advanced online edition of the journal PLOS ONE, the researchers describe an elegant method to improve aspects of lung engineering that may in the future contribute to providing a nearly limitless supply of donor organs, ideally matched to their recipients, or to repairing damaged lungs. Although years of work and further study remain before such research could be a reality in the clinic, the potential is there and the results in animal studies are promising.

The research team builds upon previous research that involves the removal of cells from the lung of a deceased individual and reseeding the resulting decellularized scaffold structure with stem cells from the lung recipient. The desired future outcome of such work would be a fully functioning lung built from the organ recipient’s own cells, therefore avoiding graft-host rejection. Although current research involves use of animal cells and scaffolds, the potential for translation to the clinic is an area of active research.

The new study, jointly funded by NIH, NASA, and a Mayo Clinic-ASU seed grant, demonstrates a number of critical advantages to conducting the cell re-population process in a dynamic suspension culture, in which the cells are allowed to gently tumble as they re-seed the decellularized lung.

“There is an urgent need for the development of lab-engineered lungs from patient stem cells that are suitable for both transplantation and as predictive models for biomedical research to probe the links between cell function and respiratory disease,” Nickerson said.

“This was an extraordinarily challenging but rewarding study that took years to complete, and we are excited that it will contribute to the current and growing body of knowledge in the field with potential downstream implications for regenerative medicine as well as identifying the underlying factors that may contribute to the transition of normal to fibrotic lung disease.”

Aurélie Crabbé, lead author of the new study (formerly with the Nickerson group and now at Ghent University, Belgium), highlights the tremendous potential for this pioneering strategy.

“Our study demonstrates that reseeding lung scaffolds under dynamic conditions could be beneficial for ex vivo lung engineering,” Crabbé said. “Dynamic culture conditions enhanced cell growth and viability, and stimulated stem cells to differentiate into matrix-producing cells as compared to static conditions – both findings might help rebuilding lungs from acellular scaffolds.

“Tremendous progress has recently been made on the use of cadaveric lungs as building blocks for the generation of new lungs, and we are hopeful that continued advancements in this field will one day provide a new source of much-needed organs.”

Nickerson and Crabbé were part of a multidisciplinary, multi-institute team, including researchers from the University of Vermont College of Medicine; Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona; and Arizona State University’s School of Life Sciences.

Pulmonary crisis

COPD is a lung disease characterized by increasing difficulty in breathing. The disease is progressive; the most common culprit is damage to the lungs caused by cigarette smoking.

The disease usually has two components, chronic bronchitis (an inflammation and partial blockage of the bronchial tubes supplying the lungs with air) and emphysema (loss of elasticity in the air sacs or alveoli of the lungs, causing shortness of breath). Cigarette smoking irritates the lung tissue and gradually destroys the malleable fibers of the lungs. Air pollution, chemical fumes, dust and secondhand smoke can also cause COPD.

Symptoms of the disease include shortness of breath, tightening of the chest and persistent cough accompanied by mucus. The underlying cause of these symptoms is scarring of the lungs (pulmonary fibrosis), which damages the lung tissue and cannot be repaired. Little is known regarding the cause of the scarring. Symptoms generally worsen with physical exercise. Flare-ups of severe symptoms, known as COPD exacerbation, become more frequent with disease progression and can be life-threatening.

COPD is usually diagnosed in middle age. The disease has no cure, and in severe cases, the only available medical intervention is organ transplantation. The clinical success of lung transplantation, however, requires lifelong immunosuppression, and chronic rejection of the new organ is common, with patients showing only 10-20 percent survival rate 10 years after transplantation.

Building designer lungs

To overcome the severe shortage of suitable donor organs and the issue of organ rejection by the recipient’s immune system, a daring new bioengineering strategy is being explored.

The idea is to remove the cells from a donor lung extracted from a cadaver, reseed the remaining decellularized scaffold with stem cells from the patient, allow the cells to adhere to the scaffold, grow and mature into the different cell types found in the functioning lung, and transplant the freshly developed, functioning organ in a living organism.

While not a reality for humans at this time, if successful in the future, this regenerative medicine approach holds the potential for a paradigm-shifting advance for sufferers of otherwise incurable lung disease.

Currently, the approach is being explored in animal models. The decellularization process is accomplished by sequentially treating lung tissues with specialized detergents, salts and enzymes. These act to remove the cellular material of the lung, leaving just the stripped-down extracellular matrix – a kind of scaffolding on which the new lung will be constructed using stem cells from the recipient.

To date, studies in which decellularized lungs from rodents were recellularized and transplanted showed marginal success in generating functioning pulmonary tissue. Experimental efforts have thus far demonstrated only partial recellularization of alveoli, airways and pulmonary vasculature. Though the fundamental approach appears sound, significant hurdles remain before the strategy can be applied to humans.

In the current study, researchers sought to improve the recellularization of the lung scaffold in a mouse model. Two cell types were used for the recellularization process, bone-marrow-derived mesenchymal stromal (stem) cells (MSCs) and alveolar type II cells, respectively.

Stem-cell challenge

Stem cells have the remarkable ability to differentiate into virtually any form of specialized cell in the body, when placed in the proper environment. Thus, the premise of the study is that stem cells exposed to the decellularized lung scaffold will take up residence and differentiate into all the specialized cell types necessary for a complete, functioning lung, much as the skeletal frame of a house is gradually dressed with walls, roof, windows and doors.

This is an audacious challenge, given the complexity of the lung, which contains more than 50 different cell types. Accordingly, optimizing the recellularization efficiency of lung scaffolds with stem cells under conditions that mimic the parental tissue environment is critical to coax the cells to multiply and mature into the different respiratory cell types, and to achieve the long-term goal of developing functional lungs in the lab that could one day be suitable for transplantation, as well as for building models of diseased or injured lungs to understand the underlying mechanisms of why damage is happening.

In an effort to improve lung recellularization, a dynamic rotating wall vessel (RWV) bioreactor was used. In previous research, this cell-culture technique has been shown to promote growth and differentiation of stem and epithelial cells. The apparatus provides a continuous suspension of the repopulating cells, which are contained in horizontally rotating cylinders, filled with a nutrient-rich media.

The motion of the RWV bioreactor offsets the natural sedimentation of cells, creating a gentle falling of cells along with their scaffolds contained in the culture medium. The activity mimics natural conditions of fluid shear – the motion of extracellular fluid over cell surfaces, which is believed to help direct proper growth and regeneration.

In the current study, comparisons were made between standard methods of recellularization using cells grown on lung scaffolds under static conditions, and those grown dynamically in a rotating bioreactor.

Cell fates

The results showed markedly different outcomes for cells grown under static and dynamic conditions. The decellularized lung scaffolds recellularized with mesenchymal stem cells for a total of 14 days displayed more abundant cells in the bioreactor, compared with static conditions. As a consequence, the quantity of RNA detected in recellularized lungs grown under bioreactor conditions was on average 3.8 times higher than for static recellularization.

Cells were more homogeneously distributed across the recellularized lungs raised in the bioreactor, compared with their static counterparts. In the case of C10 epithelial alveolar cells, static conditions yielded poor recellularization results, with abundant cell debris and low RNA compared with an abundance of intact cells cultured in the bioreactor. Both MSCs and C10 cells exhibited lower rates of cell death or apoptosis and higher cell proliferation in bioreactor vs. static recellularization conditions.

The authors speculate that biomechanical forces like fluid shear and accompanying changes in oxygenation, nutrient availability and waste dispersal, may contribute to the improved trajectories for cells grown in the dynamic suspension bioreactor system (RWV).

Also, when grown in the RWV, the stem cells expressed phenotypic markers of matrix-producing cells, or fibroblasts. This cell type normally contributes to fibrosis in the lungs of patients with COPD and other lung diseases, leading to the generation of afunctional scar tissue. However, in the context of ex vivo lung regeneration using acellular scaffolds, these fibroblast-like cells could help rebuild the matrix, which is normally deteriorated due to the chemical treatment. Therefore, the differentiation of stem cells into fibroblast-like cells under dynamic culture conditions in the RWV might generate a microenvironment that is beneficial for other cell types to grow and differentiate into the desired functional lung tissue.

In addition to furthering the immediate goals of the project focused on transplantation, study of decellularized scaffolds also provides a novel means of studying cell-matrix interactions and other aspects of normal and diseased lung biology. Such studies will advance our understanding of how normal lung tissue becomes fibrotic, with potential for novel strategies to repair damaged lung tissue.

“Imagine, if we can one day create a fully functional normal or fibrotic lung in the lab, understand the reasons why it behaves the way that it does, learn the tipping points that cause it to transition either way, and test how preventative therapies work,” Nickerson said.

“The potential findings could have tremendous implications for diagnosis, treatment and prevention for a variety of respiratory disorders, including those due to infectious disease, cancer and environmental toxins.”

---

More information: “Recellularization of Decellularized Lung Scaffolds Is Enhanced by Dynamic Suspension Culture.” PLoS ONE 10(5): e0126846. DOI: 10.1371/journal.pone.0126846

Journal reference: PLoS ONE

Read More

Sensitive Blood Test May Help Rule Out Heart Attack

WEDNESDAY Oct. 7, 2015, 2015 — A new, highly sensitive blood test may help doctors quickly rule out heart attack for almost two-thirds of people who seek emergency room treatment for chest pain, a new study suggests.

Researchers said their findings could potentially reduce unnecessary hospital admissions and substantially lower health-care costs. “Until now, there were no quick ways to rule out a heart attack within the emergency department,” said the study’s lead author, Dr. Anoop Shah, from the University of Edinburgh in Scotland.

“Over the last two decades, the number of hospital admissions due to chest pain has tripled. The overwhelming majority of these patients do not have a heart attack,” Shah said. Assessing a possible heart attack requires lengthy stays in the ER or hospitalization for repeat testing, the study authors pointed out.

The new test is more sensitive than the standard version, Shah’s team said. It can detect far lower blood levels of troponin, a protein released when heart muscle is damaged. The more damage that occurs, the higher blood levels of troponin will be. A slight increase in troponin suggests some damage has occurred, while very high levels indicate a person has had a heart attack, the researchers explained.

Using this new test, doctors could potentially double the number of low-risk patients able to be safely discharged from the emergency room, the researchers reported in the Oct. 8 issue ofThe Lancet.”Use of this approach is likely to have major benefits for both patients and health-care providers,” Shah said in a journal news release.

For the study, the researchers measured troponin levels in more than 6,000 patients admitted to the hospital with chest pain, and assessed their risk for heart attack and death from heart attack within 30 days.

The investigators found that 61 percent of the patients with a troponin level below 5 ng/L (nanograms per liter of blood) were at very low risk of heart attack and could have been discharged early, regardless of age, gender, and risk factors for heart disease. One year out, these patients had a three times lower risk of heart attack and cardiac death than those with higher troponin levels, the researchers said.

The authors of an accompanying editorial in the journal said patient follow-up will be needed to validate use of this test in routine practice.”Trials are needed to assess the safety and effectiveness of clinical pathways that involve no further testing for such patients,” wrote Martin Than from Christchurch Hospital, New Zealand, and colleagues.

---

More information

The American Heart Association describes the symptoms of heart attack.

Read More

Insight into cancer resistance in elephants could aid human treatment !!!!

They are the largest land animals in the world, weighing up to 14,000 pounds and standing up to 4 meters tall. Given their size, elephants should be highly susceptible to cancer – they have at least 100 times more cells than humans – but they rarely develop the disease. In a new study, researchers shed light on the mechanisms behind elephants’ resistance to cancer – information that could fuel knowledge on cancer resistance in humans.

Study leader Dr. Joshua D. Schiffman, of the University of Utah School of Medicine, and colleagues publish their findings in JAMA.

Theoretically, an animal’s cancer risk should increase with their size and lifespan; the bigger an animal is, the more cells they have, which should increase the rate of cell division and susceptibility to gene mutations.

In 1975, however, a study by Dr. Richard Peto, of the University of Oxford in the UK, challenged this notion. He observed that cancer incidence across species is not dependent on an animal’s size or lifespan – a theory that is now hailed “Peto’s Paradox.”

A good example of this theory is the disparity in cancer incidence between humans and elephants; despite elephants being significantly larger than humans, their risk for cancer is much lower.

Previous research has suggested that specific molecular mechanisms in elephants protect them against cancer, though Dr. Schiffman and colleagues note that such mechanisms are poorly understood.

For this latest study, the team set out to learn more about the disparities in cancer mortality rates across different mammals, with a specific focus on elephants, and to shed light on possible mechanisms that induce cancer resistance in different species.

ELEPHANTS HAVE MULTIPLE COPIES OF KEY TUMOR-SUPPRESSOR GENE

The researchers assessed information on disease and cause of death for 36 mammalian species, including African or Asian elephants.

The genomes of all species were assessed, as well as the activity of peripheral blood lymphocytes – a type of white blood cell – among elephants, healthy humans and patients with a disease called Li-Fraumeni syndrome (LFS), a rare inherited condition that greatly increases the risk for cancer. This was to assess response to DNA damage.

Overall, the researchers found that cancer mortality rates did not increase with the size or lifespan of a mammal. For example, the cancer mortality rate for elephants was only 4.8%, compared with an 11-25% cancer mortality rate in humans.

The team also revealed that elephants possess at least 20 copies of a major tumor-suppressor gene called TP53, while healthy humans only have one copy, with two alleles (gene variants) inherited from each parent. People with LFS only inherit one functioning allele of the TP53 gene, according to the team, putting them at a 90-100% lifetime risk for cancer.

The researchers explain that the TP53 gene plays a key role in the response to DNA damage by triggering a form of cell death called apoptosis via the p53 protein. Compared with human lymphocytes, the researchers found that elephant lymphocytes were subject to p53-induced apoptosis at higher rates.

Based on their findings, the team suggests the additional copies of the TP53 gene and increased p53-induced apoptosis in elephants have evolved to protect them against cancer.

The authors write:

“Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage.

These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.”

HUMAN CANCER VULNERABILITY LIKELY DOWN TO MODERN LIFESTYLE FACTORS

In an editorial linked to the study, Mel Greaves, PhD, of the UK’s Institute of Cancer Research, says the theory that elephants may be protected against cancer due to the acquisition of multiple copies of the TP53 gene seems “plausible.”

However, Greaves notes that it is unclear what implications the findings have for cancer in humans. “Perhaps the main message from this innovative investigation is to bring into focus the question of why humans appear to be so ill-adapted to cancer, given the average size and life span,” he speculates.

“The human genome is replete with footprints of positive selection in the not-too-distant historical past. Humans may have acquired, in one particular respect, an extra cancer suppressor gene variant early on in evolutionary history approximately 1.8 million years ago,” Greaves continues.

He points out, however, that modern humans are particularly vulnerable to cancer, which is more down to lifestyle factors – such as smoking – that are not seen in other animals. “These behaviors are relatively recently acquired by humans, over a few hundred years, and the risks they impart far exceed prior and otherwise effective cancer suppressor mechanisms that were inherited from primate ancestors,” explains Greaves.

Read More

Beetroot supplementation and hypertension

Beetroot supplementation lowers daily systolic blood pressure in older, overweight subjects

A. Jajja a, 1, A. Sutyarjoko a, 1, J. Lara a, K. Rennie b, K. Brandt c, O. Qadir c, M. Siervo a,a Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK b Centre for Lifespan and Chronic Illness Research, University of Hertfordshire, Hatfield Hertfordshire, AL10 9AB c Human Nutrition Research Centre, School of Agriculture, Food & Rural Development, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK

A B S T R A C T

Although inorganic nitrate and beetroot juice supplementation are associated with decreased systolic blood pressure (BP), these results have primarily been obtained from short-term trials that focused on healthy young adults. Therefore, we hypothesized that oral supplementation of beetroot juice concentrate would decrease systolic BP in overweight older participants but that the decline in BP would not be sustained after a 1-week interruption of the beetroot juice supplementation. For 3 weeks, 24 participants were randomized to either the beetroot juice concentrate or blackcurrant juice group, with a 1-week post supplementation phase (week 4). Changes in systolic and diastolic BP were assessed during the supplementation and post supplementation phases. Blood pressure was measured using 3 different methods:
(1) resting clinic BP, (2) 24-hour ambulatory BP monitoring, and (3) home monitoring of daily
resting BP. The first 2 methods were applied at baseline and after weeks 3 and 4. Daily measurements were conducted throughout the study, with 21 subjects completing the study (beetroot/blackcurrant = 10/11; male/female = 12/9; age = 62.0 ± 1.4 years; body mass index = 30.1 ± 1.2 kg/m2). After 3 weeks, beetroot juice supplementation was not associated with significant changes in resting clinic BP or 24-hour ABPM. Conversely, beetroot juice concentrate reduced daily systolic BP after 3 weeks (−7.3 ± 5.9 mm Hg, P = .02); however, the effect was not maintained after the interruption of the supplementation (week 4, 2.8 ± 6.1 mm Hg, P = .09). In overweight older subjects, beetroot juice concentrate supplementation was associated with beneficial effects on daily systolic BP, although the effects were not significant when measured by 24-hour ABPM or resting clinic BP.

Read More

Coconut Oil for Alzheimer’s Disease?

Leilani Doty University of Florida Cognitive & Memory Disorder Clinics, Department of Neurology, Florida, 32610-0236, USA

Abstract 

An estimated 5.4 million people in the United States diagnosed with Alzheimer’s disease or related disorders (ADRD) receive about $210 billion worth of unpaid care annually from about 15 million loved ones. As these numbers grow, the urgency builds to discover causes, treatments, and cures. Ever searching for promising, effective, and less expensive treatments, family caregivers are eager to adopt treatments, promoted strongly in the media. Coconut oil, especially virgin coconut oil, has starred in recent years in several internet and newspaper anecdotes as providing significant cognitive improvements in people with ADRD. A comprehensive literature review found only two studies examining the impact of coconut oil in humans though neither study dealt with ADRD. Research on dementia leading to diminishing cerebral glucose metabolism has reported on the benefit of ketone food. More controlled research is needed about the value of ketone foods, such as the varieties of coconut oil and MCT Oil. Though well researched the FDA-regulated (2009) ketone-medical-food Axona® which contains some coconut oil ingredients has shown evidence of cognitive improvements in people with mild to moderate Alzheimer’s disease but more research is needed to clarify individual sensitivities, side effects, and health risks such as acidosis or hypocalcemia, possible with long-term use by people with ADRD.

Read More