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Mayo Clinic Unravels A Mystery Disease For Minnesota Lawyer

By Dan Browning, Star Tribune (Minneapolis) (TNS)

ROCHESTER, Minn. –– Greg Widseth didn’t know what hit him.

The lawyer felt fine as he coached his son’s ninth-grade basketball workout last March. He remembers smiling at a young woman as he left the building.

Now Widseth, who once had a photographic memory, is struggling to reconstruct the events that put him in the hospital and led his wife, a former emergency room nurse, to seek help from the Mayo Clinic.

Specialists at Mayo determined that Widseth, 47, was hit by a rare disease that prompted his immune system to attack his brain cells, resulting in as many as 60 seizures a day.

Mayo is one the world’s leaders in the diagnosis and treatment of autoimmune neurological diseases, an emerging specialty that drives about 2,500 patients a year to seek help at its Rochester campus. Widseth said neurologists near his home had no idea what to do for him after standard anti-seizure drugs failed to stop the lightning jolting his brain.

“They were like, ‘Well, it just happens,'” said Widseth’s wife, Nan. “No, it doesn’t just happen,” she said, recalling that her husband didn’t even recognize her after the first seizures struck.

When it became clear that her husband wasn’t getting better, she called her sister in Rochester, whose neighbor happened to be Dr. Jeffrey Britton, a Mayo neurologist specializing in autoimmune encephalitis. Britton and his colleague, Dr. Andrew McKeon, a neuroimmunologist, agreed to see Widseth within a few days.

Special blood and spinal fluid tests developed by Mayo Medical Laboratories confirmed that Widseth had antibodies known to target certain brain cells. That prompted a round of immunosuppressant drugs that had him feeling nearly normal in just four days.

“It was like a light switch was turned off,” Widseth said.

Patients who don’t get prompt immunosuppressant therapy can suffer serious memory problems or permanent seizures, Britton said. “Getting here quickly made a huge difference.”

In the 1960s, scientists discovered that patients with some types of cancer can develop autoimmune disorders that attack the central nervous system. The immune system sends antibodies to attack the cancer, but sometimes they “cross-react” with normal brain cells, leading to neurological diseases, Britton said.
“It’s kind of an innocent-bystander effect,” he said.

Then Mayo researchers started seeing patients who had nerve diseases without the underlying cancers, and it occurred to them that the patient’s antibodies might be to blame.

Widseth had one of the more common ones, known to attack the brain’s limbic system, which is involved in the emotions, memory and learning. But he had no cancer.

Some patients have a fever shortly before the onset of their illness, so it’s thought that perhaps they had an infection that set off the immune system, Britton said.

Not Widseth. The mystery deepened.

“I would say at least half the people I’ve seen don’t have an obvious trigger that we can pinpoint,” Britton said. “So we don’t know right now what sets it off.”

Dr. Sean Pittock set up the nation’s first autoimmune neurology clinic at Mayo in 2006, and he now directs the Neuroimmunology Laboratory and the Center for MS and Autoimmune Neurology. He said technological advances in the past decade have led to “an explosion” in the identification of antibodies that trigger neurological disorders.

Autoimmune responses have been identified as the cause behind a variety of diseases, including dementia, epilepsy, encephalopathy and some eye diseases and movement disorders, Pittock said.

Some forms can even mimic psychiatric disorders, such as a potentially lethal one with the unwieldy name anti-NMDA receptor encephalitis. Susannah Cahalan, a reporter with the New York Post, brought attention to the disease in her bestselling memoir, Brain on Fire: My Month of Madness, which is being made into a movie.

More recently, Dallas Cowboys tackle Amobi Okoye spent three months in a medically induced coma as he fought the disease.

Recent research suggests the disease may be triggered in encephalitis patients by the same herpes simplex virus responsible for cold sores.

Last April, Mayo published the results of a trial evaluating patients with presumed autoimmune epilepsy in the journal Neurology. Now the idea is spreading to other neurological diseases.

Autoimmune spinal cord disease and autoimmune vision problems “have also been revolutionized by Mayo labs,” Pittock said.

Now, Pittock said, researchers are exploring autoimmune disorders that cause serious, painful gastrointestinal disease. “Remember, the gut has 100 million neurons,” he said.

Since getting the right diagnosis, Widseth has been able to stay on the job and said he’s grateful he got treatment before much damage was done.

“I’ve tried eight felony cases to verdicts,” he said.

Widseth admits to struggling with some memory lapses, some of which may be permanent. But he’s found techniques to keep him on task, such as keeping good lists and asking people to put important things in writing. Only time will tell if he’s out of danger.

“Relapse happens in about 25 percent of the cases — but that’s usually in the first year,” Widseth said. “I’m almost beyond that.”

(c)2015 Star Tribune (Minneapolis), Distributed by Tribune Content Agency, LLC

Photo: Deedre Gillis, a registered EEG technician at the Mayo Clinic, wires up Polk County Attorney Greg Widseth for a checkup on an electroencephalogram on March 19, 2015 in Rochester, Minn. (Dan Browning/Minneapolis Star Tribune/TNS)

Massive Blast Of Measles Vaccine Wipes Out Cancer

By Dan Browning, Star Tribune (Minneapolis)

MINNEAPOLIS — Stacy Erholtz was out of conventional treatment options for blood cancer last June when she underwent an experimental trial at the Mayo Clinic that injected her with enough measles vaccine to inoculate 10 million people.

The 50-year-old Pequot Lakes mother is now part of medical history.

The cancer, which had spread widely through her body, went into complete remission and was undetectable in Erholtz’s body after just one dose of the measles vaccine, which has an uncanny affinity for certain kinds of tumors.

Erholtz was one of just two subjects in the experiment and the only one to achieve complete remission. But the experiment provides the “proof of concept” that a single, massive dose of intravenous viral therapy can kill cancer by overwhelming its natural defenses, according to Dr. Stephen Russell, a professor of molecular medicine who spearheaded the research at Mayo.

“It’s a landmark,” Russell said in an interview last week. “We’ve known for a long time that we can give a virus intravenously and destroy metastatic cancer in mice. Nobody’s shown that you can do that in people before.”

Until now.

The research, published online Wednesday in the journal Mayo Clinic Proceedings, represents a “benchmark to strive for and improve upon,” according to an accompanying editorial by Dr. John C. Bell of the Centre for Innovative Cancer Research in Ottawa.

“Without trying to hype it too much, it is a very significant discovery,” Bell said in an interview.

The next step is a bigger trial to see if the measles blitzkrieg works in a larger number of patients — a trial that Mayo expects to launch no later than September.

Researchers have known for decades that viruses can be used to destroy cancer. They bind to tumors and use them as hosts to replicate their own genetic material; the cancer cells eventually explode and release the virus. Antiviral vaccines that have been rendered safe can produce the same effects and can also be modified to carry radioactive molecules to help destroy cancer cells without causing widespread damage to healthy cells around the tumors. The body’s immune system then attacks any remaining cancer that carries remnants of the vaccine’s genetic imprint.

Researchers worldwide are working with a variety of cancer-killing viruses, including herpes and poxvirus, and they have produced long-lasting cures in rodent studies, Bell noted in his editorial. “Many have been tried in humans but no one has shown this type of systemic activity (seen in the Mayo study),” he said.

The Mayo research could also help solve a related puzzle. Researchers have suspected for some time that there is a threshold level of virus that is required to defeat the defense mechanisms in cancerous tumors, Bell said, and the Mayo study helps set the bar.

In addition, various viruses show an affinity for particular organs, Russell said. Pneumonia and influenza, for example, damage the lungs. Hepatitis damages the liver.

“We have a virus that can do that selectively to a tumor without at the same time causing damage to normal tissues in the body,” Russell said.

The strain that Russell used was isolated in 1954 from the throat of an 11-year-old boy named David Edmonston and has been used to safely make all of the measles vaccines used in the West, he said. The virus treats multiple myeloma tumors as food and turns them into machines to make copies of itself.

Most people have been inoculated with the vaccine, rendering it vulnerable to their immune systems. But patients with multiple myeloma often have suppressed immune systems, which can allow the virus to do its work.

The normal dose of vaccine contains 10,000 infectious units of the measles virus, Russell said. Mayo started out giving patients 1 million infectious units and gradually cranked up the dosage — but it didn’t work until Erholtz and another patient were injected with 100 billion infectious units, he said.

While the treatment worked in Erholtz, whose tumors were primarily in her bone marrow, the results weren’t sustained in the second patient, whose tumors were largely confined to her leg muscles. Russell said researchers need to study how the nature of the tumor affects the lethality of the virus.

“I think if we had been able to give bigger dose, we might have got a better outcome in that second patient,” he said.

But at least for now, there’s no second chance. Once the vaccine has been delivered, the body’s immune system will recognize it and attack it. Russell said breaking down the immune system before the treatment will be part of another upcoming clinical trial.

Researchers also may be able to bypass the immune system by taking a patient’s cells and converting them into Trojan horses. The virus is loaded into the cells, and they are injected back into the bloodstream. “That way it doesn’t get destroyed before it reaches its target,” Russell said.

At the James Cancer Hospital and Solove Research Institute in Ohio, Dr. Tanios Bekaii-Saab is working on a study to treat pancreatic cancer using Reolysin, a proprietary variant of the virus that causes the common cold.

Researchers, he said, have two primary approaches: Inject the virus directly into tumors to get past their defenses or inject it into the bloodstream and hope it will seek out tumors and overwhelm them, as was done in the Mayo study.

Bekaii-Saab said he expects one of these virus “platforms” is likely to become standard treatment for a cancer such as myeloma or pancreatic cancer within three to four years.

After reading a draft of the Mayo study, Bekaii-Saab called it “an incredibly innovative way to actually attack the cancer and perhaps even offer a better chance at complete remission,” especially in combination with radioactive molecules and immune system therapy.

He cautioned that the study still must be confirmed in large randomized clinical trials — the point where many hopes get dashed.

“Unless we get to the third stage of development, we are only cautiously optimistic,” he said.

For her part, Erholtz has no regrets about participating in the study and remains optimistic that she will remain cancer-free at her annual checkup next month in Rochester.

“We don’t let the cancer cloud hang over our house, let’s put it that way, or we would have lived in the dark the last 10 years,” Erholtz said.

Photo via Wikimedia commons