CRISPR Gene Editing Fixes Muscular Dystrophy in Dogs. Are Humans Next?

The powerful gene editing technology CRISPR is one small step closer to treating a human disease.

By ALICE PARK 

August 30, 2018

In a new paper published in Science, researchers led by Eric Olson, professor and chair of molecular biology at UT Southwestern Medical Center, reported that he and his team successfully used CRISPR to correct the genetic defect responsible for Duchenne muscular dystrophy in four beagles bred with the disease-causing gene. It’s the first use of CRISPR to treat muscular dystrophy in a large animal. (Previous studies had tested the technology on rodents.) In varying degrees, the genetic therapy halted the muscle degradation associated with the disease.

Duchenne is caused by mutations in the dystrophin gene, which codes for a protein essential for normal muscle function. People born with the disease are often eventually confined to wheelchairs as their muscles continue to weaken, and in the later stages, many rely on ventilators to breathe as their diaphragm muscles stop working. Eventually, they develop heart and respiratory failure.

Olson and his team “fixed” the mutated dystrophin gene in four dogs by splicing out an offending section of the gene using CRISPR. The gene editing technology, discovered in 2012, can cut out sections of DNA at precise locations (and also potentially introduce new DNA as well). In the case of Duchenne, says Olson, simply snipping out a section of the mutated dystrophin gene allows the gene to make enough of the proper protein that muscles need to function.

Olson tried two different methods of injecting the CRISPR molecular scissors. With two dogs he directly injected the CRISPR technology into muscle, while in two other dogs he injected the same CRISPR technology into the bloodstream, so it could travel to more parts of the body and have a broader effect on different types of muscle from the limbs to the heart and diaphragm. Because Duchenne seems to affect the heart and respiratory system muscle preferentially, he also loaded the CRISPR cutting complex onto a molecular vehicle, a cold virus that was modified to seek out and splice DNA in those muscle cells in particular.

“I was frankly exuberant by the results,” says Olson. “It was jaw dropping.”

In the dogs that had received the systemic injections, he found that muscle cells in various parts of their bodies, including the heart and diaphragm, were churning out healthy dystrophin protein at anywhere from 3% to 90% of the normal levels eight weeks after injection. Olson says that muscular dystrophy experts believe that if dystrophin levels in affected people were raised to 15% of normal, it would make a dramatic difference in their lives and their ability to function. The dogs receiving the CRISPR injections directly into their muscle also showed higher levels of dystrophin production, but just in those muscles specifically. Because Duchenne affects deep organs like the heart and respiratory system, Olson says finding a way to deliver CRISPR more widely, without repeated and multiple injections, is preferable.

The idea is that CRISPR would essentially delete the mutation in muscle cells, and return the affected dogs to a nearly normal state. So far, the animals continue to make higher amounts of dystrophin after eight weeks.

The study is the latest in an encouraging string of results in applying CRISPR to treat human disease. Researchers have also successfully used the gene editing technology to splice out HIV from both infected human cells in the laband in living mice and rats, and are close to beginning trials to blood disorders like beta thalassemia and sickle cell anemia. Scientists have even corrected a genetic heart defect in embryos in the lab, which were not allowed to develop further or be implanted for ethical reasons. While serious questions about the safety of CRISPR-based therapies remain — some studies revealed greater than expected side effects from overzealous DNA snipping, for example — both academic and commercial researchers remain committed to investigating CRISPR as a new tool in addressing genetic diseases such as Duchenne.

Olson is encouraged by the results, even if they came from just a few dogs. They provide some reassurance that Duchenne, which is often diagnosed before people start to notice symptoms of muscle weakness, might be halted in its tracks before important skeletal, heart and breathing muscle are damaged beyond saving. A CRISPR-based therapy, he says, may be most effective in treating young people recently diagnosed with the disease, to prevent them from ever experiencing the symptoms of Duchenne.

Even people with more advanced disease might benefit, Olson thinks, as long as there is some muscle left to maintain a certain level of function, whether that’s moving the legs and arms or keeping the heart functioning. “I absolutely believe that whatever stage we intervene with this therapy, it could halt or slow the progression of the disease from that point forward,” he says.

First, however, more studies need to be done in larger animals like dogs. Olson is planning on a longer term study to see how long the CRISPR cells remain in the dogs, and how safe the therapy is.

The hope is that if those animal studies and human trials prove this technique is safe and effective, CRISPR could potentially lead to a cure for Duchenne, Olson says. “We are going for a cure, not a treatment,” he says. “All of the other therapies so far for Duchenne muscular dystrophy have treated the symptoms and consequences of the disease. This is going right at the root cause of the genetic mutation.”

http://time.com/5382101/crispr-muscular-dystrophy-in-dogs/

Can This Banned Condiment Boost Brain Function? (Marmite)

Not many in the US eat Marmite, the British version of Australia's savory spread known as Vegemite. Somewhat controversial in some countries (for an...

April 17, 2017 

Story at-a-glance

• Marmite, the U.K. version of Vegemite, is a salty spread made since the 1800s from yeast extract and now shown by researchers to have numerous compounds to enhance your health
• A single serving of Marmite provides 36 percent of the Reference Daily Intake (RDI) recommended for niacin, 50 percent of the RDI in folic acid and 40 percent of the RDI in vitamin B12, as well as other B vitamins
• Marmite may increase gamma-aminobutyric acid (GABA) levels to optimize brain function and stave off cognitive disorders such as Alzheimer’s
• Studies show Marmite to be better than peanut butter in terms of its ability as a brain booster, can successfully treat anemia and helps protect your body against resistant bacteria, including MRSA

By Dr. Mercola

Perhaps you first heard about Vegemite in the early 1980s from the Men at Work song, "Down Under."

The Australian sandwich spread, described by the Telegraph as a sticky, gloopy, salty spread made from yeast extract, may be the flavor that embodies the entire continent, as 23 million jars are purchased in Australia every year.1

Vegemite's first cousin, Marmite, is the British version of the controversial condiment. Both are considered an acquired taste, but it's the latter that's been scrutinized in scientific circles and found to contain some very impressive properties for the human body.

In fact, several studies show it contains vital nutrients, including 40 percent of the reference daily intake (RDI) for vitamin B12, 50 percent for folic acid and 36 percent for niacin, helps to protect against antibiotic-resistant superbugs such as MRSA and boosts gamma-aminobutyric acid (GABA) levels to restore optimal brain balance.2

Invented in the late 1800s, Marmite came first, followed by Vegemite, invented in the 1920s. In fact, Marmite was included in the ration packs English soldiers carried during World War I. The high level of different B vitamins is also attributed to its effectiveness as a mosquito repellent.

The Daily Meal describes the dark, rich sauce as "full of umami and, at first blush, one of the most disgusting things most Americans have ever tried."3

The British are serious about their Marmite. Owned by Unilever, the company's spoof Ministry of Marmite exists "to enrich the existence of all Marmite lovers, whether resident in the U.K. or overseas, through the comprehensive application of Marmite in every facet of their domestic, professional, cultural and social lives."4

Brits and Aussies are wild about their respective yeast extracts like many Americans are about jam on their morning toast, but Marmite isn't sweet like jelly and marmalade; it's umami, the newest flavor among the basic tastes of sweet, sour, salty and bitter. Umami is the Japanese word for "delicious," which in English means "savory."

Popular as a meat flavor for vegetarians, this yeast-based paste can be stored at room temperature and, although it might dry out, remains edible for years, according to the International Business Times (IBT).5 One must ask what's in it to give it such a remarkable calling card.

Sweden Not a Fan: Marmite's Controversial Components

The main ingredients in Marmite are yeast extract, vegetable extract and salt augmented with thiamin, folate, riboflavin, niacin, iron and vitamin B12. It's flavored with things like celery extract, although the exact ingredients and the amounts are a carefully guarded and undisclosed recipe.

The Marmite website reports that a jar contains 100 grams (just over 3.5 ounces) with 34 grams of protein, 30 carbs, 1.2 grams of sugar and 10.8 grams of salt.6 In spite of its strong flavor, some consider Marmite to be a bona fide superfood. According to Daily Mail:

"Both products are made via a complex method in which salt is added to a suspension of yeast and then heated, resulting in a rich paste loaded with free glutamic acids, also known as umami (it's the primary component of MSG).

The exact recipe is a secret, but various vegetable extracts and vitamins are also added."7

The glutamic acid in MSG, or monosodium glutamate, is an excitotoxin, which means it overexcites your cells to the point of damage or death. But the glutamic acid found in nutritional yeast binds to and is absorbed by other amino acids or proteins, while what is found in MSG is not. In essence, your body controls the glutamic levels.

While Marmite isn't exactly banned in Sweden, the government requires retailers to obtain special permission from the Danish Veterinary and Food Administration to place it on their shelves. IBT explains it this way:

"The paste is made by adding salt to the yeast by-product from breweries, heating the solution until the cell walls of the yeast are softened, then straining the solution to make it smooth.

The result is naturally rich in vitamins, especially the Vitamin B complex, but additional vitamins and minerals are added to Marmite — and that is what the Danish government dislikes."8

While in the U.S. Marmite barely shows up on the radar in terms of nutrition, it's been lab tested and declared better than peanut butter in terms of its ability as a brain booster. Recent studies have determined that the savory substance may increase your brain's neurotransmitters, the function involving messaging.

Marmite May Boost Your Brain's GABA Levels

Of course, it was a study based in the U.K., kicked off when researchers found that a single teaspoon of Marmite, taken daily by study participants, prompted a decrease in neural response to visual stimuli.

Scientists at the University of York said that's an indicator of increased gamma-aminobutyric acid (GABA) levels.9 According to Medical News Today:

"GABA is a neurotransmitter responsible for inhibiting the excitability of brain cells, helping to restore the optimal balance of neuronal activity required for healthy brain functioning. Put simply, GABA 'calms' the brain.

Previous studies have associated low GABA levels with an increased risk of numerous neurological and mental health disorders, including anxiety, depression, autism and epilepsy. As a result, researchers have been investigating ways to boost GABA levels in the brain."10

Study author Daniel Baker, Ph.D., used data from 26 adults, divided into two groups. One group was directed to eat a teaspoon of Marmite every day for a month, while the others ate the same amount of peanut butter.

Thirty days later, the study subjects underwent electroencephalography to measure brain activity in response to visual stimuli in the form of flickering lights.

The latter group had a 30 percent decrease in neural response to visual stimuli in comparison to the Marmite group but, even better, those responses were ongoing for another eight weeks.

The result was similar to that resulting from an animal study in which there was a 300 percent decrease in neural response to visual stimuli. The study concluded:

"This 'response gain' effect should provide a clear index of GABA availability in cortex, in that increasing GABA concentration should reduce the neural response evoked by visual stimuli to below normal levels."11

Baker said the main reason for the significantly reduced responsiveness to visual stimuli in the participants was most likely the high concentration of vitamin B12 in the Marmite.

Interestingly, while the scientists stressed that therapeutic recommendations couldn't yet be made, they touted the study as the "first example of how dietary interventions can alter cortical processes."12

B Vitamins: 'Super' Compounds in Marmite

According to the Journal of Clinical Investigation,13 niacin, or vitamin B3, one of the main ingredients in Marmite, helps protect your body against staphylococcus bacteria. The Telegraph reports that in tests, niacin:

" … [P]roduces neutrophils, a white blood cell that fights bacteria — [and] increased our immune system's ability to kill different strains of the bugs by up to 1,000 times.

This could mark a turning point in the battle against antibiotic-resistant superbugs, such as MRSA, the deadly strain that poses a threat in hospitals."14

Folate, vitamin B6 and vitamin B12 are essential for converting what could become a damaging molecule, called homocysteine, into the amino acid cysteine in a process called the methylation cycle.

Without this suppression mechanism, studies show heart disease and Alzheimer's to be an increased risk, as homocysteine can lead to brain and blood vessel deterioration. According to the George Mateljan Foundation:

"Homocysteine promotes atherosclerosis by directly damaging blood vessel walls and by interfering with the formation of collagen (the main protein in connective tissue).

Elevations in homocysteine are found in approximately 20 [to] 40 percent of patients with heart disease, and it is estimated that daily consumption of 400 mcg of folate alone would reduce the number of heart attacks suffered by Americans each year by 10 percent."15

Further, high levels of homocysteine not only are linked to blood vessel damage, but are often found in Alzheimer's patients, suggesting that many people all over the world may be suffering from a "Marmite" (or B vitamin) deficiency.

Other brain and mental capacities positively influenced by vitamin B3, or niacin, found liberally in Marmite, include attention deficit hyperactivity disorder (ADHD), anxiety, depression and obsessive-compulsive disorder. And B12 deficiency can trigger different types of psychoses and paranoia. Unfortunately, this deficiency is common.

SEE ALSO:  The Importance of B Vitamins for Brain Health and Combating Dementia

How an Early Scientist Discovered One of Marmite's Most Important Benefits

In the 1930s, English scientist Lucy Wills discovered that the folic acid content in Marmite could successfully treat anemia. In studying whether a vitamin deficiency might contribute to what was at the time called pernicious anemia of pregnancy, one review noted her research on the effects of Marmite, a "cheap yeast extract," on monkeys:

"One particular monkey did especially poorly, and for reasons which are not recorded — perhaps in desperation — she tried the cheap yeast extract, Marmite. It had a dramatic effect. Thus, after all the intensive examination of diets and exhaustive testing on rats, it was a chance intervention with a single animal that led to the breakthrough. Wills had taken the first step to the discovery of folic acid."16

According to nutritionist Melanie Brown, who specializes in pre-conception and pregnancy nutrition, Marmite can help pregnant women through morning sickness, as well as help elderly individuals who have lost their sense of taste.

High Salt Content Leads to Marmite Bans, but —

Denmark, which hasn't sold Marmite since May 2011, isn't the only country to look unfavorably on the savory condiment that a large portion of the known world swears it can't live without. The powers-that-be in Ceredigion, Wales, banned Marmite in elementary schools in 2008.

Oregon State University jumped on the bandwagon and began warning people not to take high "doses" of the stuff without medical supervision due to its high salt content. However, salt is not the ogre it's been made out to be. In fact, not enough salt in your diet isn't good for your heart. The more important question is whether or not your salt quotient is properly balanced with that of your potassium intake.

http://articles.mercola.com/sites/articles/archive/2017/04/17/marmite-boosts-brain-function.aspx

SEE ALSO:

• Marmite may be brain food, study says
• Marmite the 'cure all' spread
• Little sympathy for Unilever in town where Marmite is made
• Can This Banned Condiment Boost Brain Function? (Marmite)
• The Importance of B Vitamins for Brain Health and Combating Dementia

Iron in Your Blood and Anemia Drugs - MUST READ

...an investigation by the Washington Post revealed the benefits were “wildly overstated, and potentially lethal side effects, such as cancer and strokes, were overlooked”

Anemia Drug Made Billions but at What Cost?

August 22, 2012

Story at-a-glance

• Three anemia drugs -- Epogen, Procrit and Aranesp -- have been among the best-selling prescription drugs in the United States for years, generating more than $8 billion a year for their makers, Amgen and Johnson & Johnson
• After millions of people have taken these drugs, an investigation by the Washington Post revealed the benefits were “wildly overstated, and potentially lethal side effects, such as cancer and strokes, were overlooked”
• Thanks to the drug companies’ lobbying, doctors and hospitals received major incentives for prescribing the drugs, particularly at high dosages
• Effectiveness claims were based on a series of incomplete and never-published research, some of which were drawn out over a decade or more only to show inconclusive results; safety data was also misleading, and concerning results showing a higher risk of death and heart attacks in patients taking higher doses of the drugs were downplayed
• No major class-action suits have so far been filed against the drugs’ makers; it is, unfortunately, often difficult to prove the drugs were the cause of death, particularly because patients who received them were typically already facing chronic health problems and were on a multitude of other prescriptions

By Dr. Mercola

Three anemia drugs – Epogen, Procrit and Aranesp – have been among the best-selling prescription drugs in the United States for years, generating more than $8 billion a year for their makers, Amgen and Johnson & Johnson.

They were blockbuster drugs that stimulate your body to produce new red blood cells, which supposedly helped boost kidney and cancer patients' energy and, ultimately, enhanced their lives.

But now, after millions of people have taken these drugs, it's come out that the benefits were "wildly overstated, and potentially lethal side effects, such as cancer and strokes, were overlooked."1

Worse still, the Washington Post has uncovered a series of unsettling events that show just how far drug makers were willing to go to get rich…

Doctors Earned Profits of Up to 30 Percent Just for Prescribing the Drugs

And this was one of the first problems. Drug makers lobbied Congress in order to put a system into place so that doctors and hospitals would be reimbursed more for the drugs they prescribed to Medicare patients than what they actually paid for them. The markup could be as high as 30 percent, and the higher the dose prescribed, the more money they made.

According to Charles Bennett, endowed chair at the Medication Safety and Efficacy Center of Economic Excellence at the University of South Carolina, in the Washington Post:

"It was just so easy to do – you put this stuff in the patient's arm, and you made thousands of dollars… An oncologist could make anywhere from $100,000 to $300,000 a year from this alone. And all the while they were told that it was good for the patient."

Higher Doses Pushed to a Growing Number of Patients

Initially, patients with kidney disease, who often suffer from anemia, were the key target market for the drugs. If anemia is severe enough, blood transfusions are required to boost red blood cell counts. Epogen, Procrit, and, later, Aranesp, were able to accomplish the same boost in blood cells without the need for transfusions.

The Washington Post reported:

"The trouble would arise as the drugmakers won FDA approval for vastly expanded uses, pushing it in larger doses, for milder anemia and for patients with a wider array of illnesses. Very quickly, the market included nearly all dialysis patients, not just the roughly 16 percent who required blood transfusions. The size of average doses would more than triple. And over the next five years, the FDA would approve it to treat anemia in patients with cancer and AIDS, as well as those getting hip and knee surgery.

The key to their marketing was the claim that the drugs at higher doses could make patients feel better. By 1994, the drug's label, approved by the FDA, advertised a range of benefits: 'statistically significant improvements for... health, sex life, well-being, psychological effect, life satisfaction, and happiness.'"

These claims, however, were based on a series of incomplete and never-published research, some of which were drawn out over a decade or more only to show inconclusive results. One safety study on cancer patients that was supposed to be finished in 2008 is still not complete, and won't be until 2017, according to Amgen, which will be nearly 25 years after the drugs were approved for cancer patients.

And as it turns out, the claims that the drugs lead to improved quality of life have since been withdrawn because they don't meet the U.S. Food and Drug Administration's (FDA) standards of proof.

Higher Doses Increased Patients' Risk of Dying – Study Results Missing Key Data

In 1998, the Normal Hematocrit Trial was published, which explored giving higher doses of drugs to dialysis patients in order to boost their red blood cell count above those generally achieved with transfusion.2 The study did, in fact, find that patients receiving the higher drug dose were dying or having heart attacks at a higher rate than those receiving the lower dose; the trial was actually halted because of this.

However, rather than sounding an alarm bell, when the study was published the authors downplayed the danger, calling the increased death and heart attack rate "not significant." And while no difference was found in quality of life between patients receiving the higher or lower dose, this was not noted in the published study. (Four of the study's eight authors were employed by Amgen, and two have served as consultants.)

As the years went by, health care providers and the drug companies continued to profit from the ever-rising doses of these drugs being prescribed – despite continued studies coming out questioning their safety. It wasn't until years later, in 2011, that the FDA put out a safety announcement calling for more conservative dosing of the drugs "because of data showing increased risks of cardiovascular events."3

The Washington Post reported:

"For years, a small Bethesda-based nonprofit think tank, the Medical Technology and Practice Patterns Institute, had been publishing studies that challenged the conventional enthusiasm for the drug and the government policies that it said promoted their overuse.

Then in November 2006, a study published in the New England Journal of Medicine reported that kidney patients targeted for higher doses were linked to higher risks of hospitalization, strokes and death. In December, a group of Danish researchers said that it had stopped a trial of Aranesp in cancer patients because of an increase in deaths and tumor growths. And that was just the beginning of the bad news…"

The FDA Finally Cracks Down

The Danish research seemed to be the breaking point for the anemia drug trio.

"'Then the FDA cracked down,' The Washington Post reported. 'The drugs' use was ruled out in cancer patients considered curable, it was ruled out in patients considered just slightly anemic, maximum recommended doses were lowered, and the agency told doctors in many cases to use the smallest amount possible to avoid a blood transfusion.

The agency also began to look askance at the alleged benefits, for which the evidence, in retrospect, seemed flimsy. There was no solid proof, under revised FDA guidelines for such measures, that use of the drugs leads to 'statistically significant' improvements in happiness and other benefits, the agency said. Those quality-of-life claims, once so critical to the drug's adoption, were removed from the label.

…Last year, nearly two decades after the Office of the Inspector General first suggested it, the economic incentives to use more of the drugs on patients in dialysis disappeared."

No major class-action suits have so far been filed against the drugs' makers; it is often difficult to prove the drugs were the cause of death, particularly because patients who received them were typically already facing chronic health problems. Still, Amgen has put aside a reported $780 million to settle various claims, including some for alleged illegal sales tactics – a paltry compensation to those who have lost loved ones. This is, unfortunately, just the latest drug scandal to be brought to the public's attention… and it surely won't be the last.

Pharma Giant Pfizer Fined for Bribing Officials in Eastern Europe and China

Earlier this month, it was revealed that U.S. pharmaceutical giant Pfizer and its subsidiary Wyeth have been charged with paying off officials, doctors and healthcare professionals in Eastern Europe and China to secure approval and registration of the companies' products.

The company allegedly paid millions of dollars in bribes from 2001 to 2007. The bribery was so blatant and entwined in the sales practices that they even offered points and bonus programs to improperly reward foreign officials who proved to be the best customers, according to the head of the SEC's Foreign Corrupt Practices Act Unit. Obviously, such corrupt pay-offs puts honest companies at a disadvantage, James McJunkin, assistant director of the Washington field office of the Federal Bureau of Investigation pointed out.4

And that is the over-riding theme we see again and again – these companies are typically NOT honest, yet we trust them with the most sacred possession we have, our health. For punishment, Pfizer will be paying various fines ranging from $15 million to $26 million – barely a slap on the wrist for a company that makes billions of dollars a year.

Big Pharma's Lack of Ethics, Regard for Patient Safety Seemingly Knows No Bounds

If it seems like the number of lawsuits that Big Pharma is settling – many of them out of court without going to trial – are rising, they are. From Merck's $950-million Vioxx deal to the latest announcement that Pfizer has made an $896-million settlement with Prempro victims, the deals show no signs of stopping. Most of the lawsuits are being filed in conjunction with, or aided by, the U.S. Department of Justice, many of them originating from former employees-turned-whistle blowers who divulged marketing misdoings by their employers.

The litigation and settlements are starting to rattle the drug industry, which is becoming no stranger to billion-dollar settlements. Most likely near the end of 2012, Johnson & Johnson reportedly will settle for as much $2.2 billion for its fraudulent marketing of the antipsychotic drug Risperdal.

That amount rivals what was the largest health care fraud settlement to date – $2.3 billion paid by Pfizer in 2009, also for illegally promoting uses of four of its drugs. However, now it's come out that GlaxoSmithKline has agreed to a whopping $3-billion settlement – the largest in U.S. history for health care fraud – with the U.S. government, again for advertising drugs for unapproved uses, along with using gifts to persuade doctors to prescribe the drugs.5

Unfortunately, Americans are disproportionally supporting this behemoth of an industry. Americans, including children, are the most drugged people in the entire world, with the average adult taking 11 prescription drugs – each of which comes with an average of 70 different potential side effects that are then typically addressed with even more drugs...

The situation has gotten out of hand, especially since there's a mountain of evidence supporting the use of alternatives, and there's very strong evidence that some "alternative" treatments, such as diet and exercise, are FAR more effective, not to mention safer, than any of the drugs currently in use. My site is chock full of free comprehensive recommendations that can serve as an excellent starting point to break free from this fatally flawed paradigm. The tools I provide on this site will help you to reduce your reliance on the broken health care system, including its overuse of drugs, and provide you with the tools and resources to Take Control of Your Health.

http://articles.mercola.com/sites/articles/archive/2012/08/22/blockbuster-anemia-drugs.aspx

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