Prestige sometimes springs from unfortunate circumstance.
Such was the case for Mayo Clinic in 1939 when baseball player Lou Gehrig got his devastating diagnosis of amyotrophic lateral sclerosis, or ALS, in Rochester.
As a result, Lou Gehrig's disease and Mayo Clinic will forever be inseparably linked.
Mayo researchers hope the clinic's next inextricable connection to Lou Gehrig's disease will be a patient-derived stem-cell treatment to slow — or even "arrest" — progression of the disease.
Research progress can seem to move slower than a fishing worm crawls, especially for those affected by a progressive neurological illness like ALS.
It's important to manage public expectations, said Dr. Anthony Windebank, deputy director for discovery in the Center for Regenerative Medicine at Mayo.
But he and his team are hopeful they can guide newly grown stem cells to make them protect neuromuscular function.
"We're making them from the patients," Windebank said.
Deep inside the Mayo Human Cellular Therapy Laboratory, past multiple layers of contamination-preventing security, rest vats and refrigerators containing stem-cell growth media.
Patients donate cells
The media are used to multiply fat-cell samples. The samples are donated by patients like Brian McCoy, a Rochester carpenter diagnosed with ALS in October 2012.
McCoy and 24 other patients in a Phase I clinical trial get injections of their own stem cells, to verify it's safe.
Each group of five patients gets more stem cells than the previous group, said Mayo neurologist Dr. Nathan Staff. That's the "dosing" aspect of the study, used to make sure each dose is safe and to see which dose might work best.
The first patients got a single dose of 10 million of their own stem cells.
The final group of patients will get two doses of 100 million, Staff said. The study is designed to continue following patients for two years. At each visit, patient strength is measured and patients fill out a standard ALS survey to measure ability to function in daily life.
For example, McCoy wears slip-on shoes because shoestrings have become difficult to tie.
The study is remarkable for providing hope that a treatment against the disease itself is possible. But Windebank said a previous study most-filled with hope, once results were revealed, turned out negative and researchers had to go back to the drawing board.
Ironically, Staff said, "in ALS trials, there's usually a very strong placebo effect."
"People can feel better and it can sometimes be very difficult to tell the difference between placebo effect and a real effect," he said.
Objective measure is key
That's why it's important to have an objective measure over time using the survey.
"The bad thing about this disease is you don't realize how it affects your family," McCoy said.
If the study demonstrates giving self-derived stem cells to people with ALS is safe, Staff said, it will be possible to move on to a larger, Phase II study of 48 patients to demonstrate effectiveness of the treatment.
McCoy would like people to know more about ALS as a disease. Although effects are individualized to the person, ALS has affected McCoy's speech in particular.
"It's hard for me to slow down enough for people to understand when I talk," he said recently while under observation at the Clinical Research Unit at Mayo Clinic Hospital. It's easier for him to talk when he has the most energy, during the morning hours.
MayoClinic.org indicates early symptoms of ALS can include tripping, hand and leg weakness, slurred speech, trouble swallowing, muscle cramps, trouble holding the head up and twitching in the arm, shoulder and tongue.
If the stem cells in the research study could add six months or a year to the life of a person with ALS, and include better quality of life related to symptom progression, it would be worth the effort to get the treatment, McCoy said.
Of course, researchers figure if they're able to take that first, monumental step, they might be able to add more treatment tools and continue chipping away at extending life, and quality of life, bit by bit.
Stem-cell purity is essential, said Windebank.
"You have to have very special ways to make sure they don't get contaminated," he said.
Stem-cell doses multiplied
Vats containing liquid nitrogen offer safe storage so stem-cell doses can be multiplied over time for use in patients and then stored until it's time to use them.
"If at any time the temperature started to change, there are alerts that go off," Windebank said. There are always personnel on duty in case something like that happens.
Patients selected for participation in the clinical trial visit the clinic, where a sample of fat is taken through a small incision in the belly.
That fat sample goes to the Human Cellular Therapy Laboratory, where research and development technologists like Greg Butler don booties, caps and protective clothing before entering the first security level.
Even before entering the changing room, technologists step upon sticky-tape on the floor to prevent contaminants from entering.
Once in the clean room, Butler said, technologists "digest" the fat sample.
"We break the fat apart basically, mash it up … mix it up with media and grow up our stem cells," he said. The clean room and "biological safety cabinets" are controlled at a constant temperature ideal for stem-cell growth.
Fat cells, fortunately, "kind of float" to the surface "and the stem cells kind of sink down to the bottom," Windebank said, where they actually stick to the plastic of the container, making it easier to isolate them.
This isn't a Frankenstein laboratory growing body parts. Rather, the flasks basically look like containers of colored liquid and contain stems cells invisible to the naked eye that are modified for protection of nervous tissue before injection into the spinal column during a spinal tap.
The research focus, Windebank said, is based on "unmet needs of the patient."
Return for injection
The stem cells, he said, are treated to make them "more likely to make factors protective to nerve cells," something patients' bodies aren't able to do without help.
Weeks after initial sample collection, the patient returns to get the spinal tap injection.
The purpose of using the protective stem cells is to "arrest the patient where they're at" in ALS progression.
It's unclear if stem cells might actually heal some patients even further.
Cells that are damaged in ALS are the same ones damaged in people affected by polio. The idea, Windebank said, is if the loss of cells could be kept at 20 to 30 percent "that person would probably actually have pretty good function."
Motor cells of the nerves that trigger muscle movement are the ones dying in ALS.
"As they die, they lose the muscle function," Windebank said. That can affect abilities, such as speech and swallowing. When death occurs in ALS, it is generally due to loss of breathing ability. Electronic stimulation of the diaphragm can help, but it's loss of breathing that eventually causes death, Windebank said.
The ability of patients and their loved ones to deal with their diagnoses amazes him.
"The individual patients give you inspiration," he said, calling them "amazing people."
Doesn't affect intelligence
One silver lining of ALS is that it doesn't usually affect intelligence.
"So you can be in control" of decision making, Windebank said.
Once the shock of diagnosis wears off, "they know they have a period of time." That allows affected individuals to make decisions about how to deal with the disease and its effects.
"It often brings family closer together," Windebank said. "Most of us, we don't get that chance, usually. We're taken from this earth without warning."
The Phase II study called "Brainstorm" will give the treatment to some patients and not give it to others, meaning it's "blinded" so patients won't know whether they will get their own stem cells or a placebo. Researchers also won't know who gets the stem cells and who gets placebo.
"Within two to three years we'll know whether this works or not," Windebank said.
McCoy said he remains able to stand and perform basic tasks. But ALS frustrates his ability to use clothes with buttons and it has caused him to fall recently.
He's playing a role in bringing hope to those with the unforgiving illness.
Likewise, to be a researcher, you've got to be optimistic, Windebank said.
"You've got to believe."
Health reporter Jeff Hansel writes the Pulse on Health column every Monday. Follow him on Twitter @JeffHansel.