Clinical Trial Fights ALS
http://www.usatoday.com/news/health/story/2012-08-05/clinical-trial-fights-ALS/56791326/1
DETROIT – Sometimes she glares at the painting of Jesus in her dining room.
By Kimberly P. Mitchell, Detroit Free Press
Regis Kleiss, 28, of Royal Oak, Mich., is taking part in a clinical trial to combat amyotrophic lateral sclerosis, led by the University of Michigan.
EnlargeClose
By Kimberly P. Mitchell, Detroit Free Press
Regis Kleiss, 28, of Royal Oak, Mich., is taking part in a clinical trial to combat amyotrophic lateral sclerosis, led by the University of Michigan.
Sponsored Links"I just let it loose," said Mary Kleiss at her Royal Oak home. "I look at that picture and I say, 'You get down here and put on your boxing gloves and let's get this over with.' I am so damned angry."
Her son, Regis, was diagnosed 2½ years ago with Lou Gehrig's disease, formally known as amyotrophic lateral sclerosis, or ALS. It is, he writes, "as if God is torturing me."
The disease kills with swift and stunning efficiency — deadening its victims' peripheral nerves, withering muscles and, in a final assault, shutting down their ability to breathe. An estimated 30,000 people have the disease at any given time; 5,000 are diagnosed yearly. Most die within a few years. There is no cure.
The disease has reduced Regis Kleiss, 28, a formerly thick-bodied shot and discus thrower and captain of the high school track team, to a bony echo of himself.
Paralyzed except for some minor movement he can make with his head, he will spend his final days on a feeding tube, unable to hold his bassett hound, Riley, or hug his parents or his niece or even scratch his head. And the cruelest thing of all? ALS leaves its victims' minds intact.
"It's a miserable, damned disease," his mother said.
Now, a clinical trial overseen by the University of Michigan may provide hope. It's tentative and early. But when the rest of a person's life has been compressed to an expectancy of two to five years, it is hope, nonetheless.
The trial has been based in Atlanta since 2010, but Michigan has requested approval from the U.S. Food and Drug Administration to expand it and move it to Ann Arbor. It is cutting-edge and audacious work — the only ALS trial so far in which neural stem cells are injected directly into a patient's spinal cord. So far, 15 patients have undergone the procedure — two of them twice — as the FDA monitors its safety.
One patient showed a remarkable improvement, though Michigan's Dr. Eva Feldman, who heads the research, cautions not to read too much into that.
The trial involves injecting 500,000 to 1 million stem cells into the spine. The ancestry of the line of cells dates to the spinal cord of an aborted fetus in 2000.
Feldman and others theorize that these new cells act as nursemaids to damaged nerve cells, sending out repair signals, and somehow halting the progression of the disease.
The procedure worked in rats. It has been shown to be safe in pigs.
If the FDA approves the expansion of the human trial, patients will have access to an experimental treatment that not only might offer insight into a disease that kills an estimated 15 Americans a day, but also push back the battle lines against other neurodegenerative diseases, such as Parkinson's, Alzheimer's or Huntington's.
Last month, Feldman flew down with a team of Michigan staff for the 17th surgery in the trial, in anticipation that the trial might soon move to Ann Arbor. The trial has been at Emory University in Atlanta since it began.
Feldman is clear and she repeats this often: This part of the trial tests safety only. By design, it doesn't assess the efficacy of the treatment yet.
So the clinical trial patients so far — all from the Atlanta area — know the experimental stem cell therapy probably will not cure them. Still, they're empowered, knowing their participation might one day cure others, said Ed Tessaro, a retired Macy's executive.
The following morning, Tessaro, 66, lay on an operating room table at Emory's hospital, as doctors removed part of the bone in his spine and laid bare a pulsating, bright-white spinal cord for a second infusion of stem cells.
"It may kill us," Tessaro said of the disease, "but it's not going to defeat us before we die."
'The worst thing I could tell you'
It was 2008 when a single misstep and near-stumble during a half-marathon in Bangkok, Thailand, first worried Tessaro. It happened more than once. His muscles weakened, even as he stepped up his time at the gym.
Months later, a doctor delivered the news to him and his wife, Judy.
"She said, 'It's the worst thing I could tell you,'" Judy Tessaro recalled.
"'You have ALS, and you have two to four years to live,'" Ed Tessaro added.
Tessaro took stock. Life had been good, he decided.
Tessaro has been married for 43 years. He has a daughter and son, and is a grandfather to two little girls.
Now, every conversation, every gentle touch from his wife, the babbling of his grandbabies — his senses are in now in hyperdrive.
"In retrospect, I was living in analog. What I'm now living my life in is high-definition. I'm living my life fully, because I know I have less of it," Tessaro said.
When he heard about the clinical trial, Tessaro jumped at it.
"It's not like I can hope for a miraculous reversal of this disease — it's not coming," he said. "I don't think I have anything to lose and I can be part of something bigger. It's great therapy when you commit yourself to something bigger."
He became Patient No. 12 on April 13. Doctors slipped stem cells into the lower — or lumbar — section of his spine. The area that controls lower body movement, it was considered least risky because Tessaro was already losing the strength in his legs anyway.
Tessaro survived. In fact, he left the hospital days earlier than expected and felt better sooner than he expected.
So doctors decided — and the FDA approved — a second, riskier, surgery for Tessaro. This time, doctors would move to the upper — or cervical — portion of Tessaro's spine, the area in which the nerves are responsible for breathing.
Feldman calls this area "precious real estate," the stretch of spine where researchers say they believe the treatment may be most effective.
"Higher risk, but maybe higher reward," Tessaro said, shrugging. He was in the pre-operating room of Emory University Hospital, surrounded by family and overnight bags and medical tubes and equipment.
It was July 20.
In a stretch of hallway and an elevator ride away, a nondescript FedEx box was being delivered to Dr. Jonathan Glass, director of the ALS clinic at Emory. His hands were working quickly.
An unexpected result
Ted Harada is on Page 8 of the March Journal of Stem Cells, which published the first study announcing the preliminary results of the first 12 patients.
Harada is the anomaly. Like Tessaro did last month, Harada this month will undergo a second surgery. And like with Tessaro, it took some time to diagnose the mysterious weakening of Harada's body.
The former FedEx managing director, now 40, noticed he was getting winded in 2009 while playing Marco Polo in the family pool with his three children: "I'd go under water and come back up, and I was sucking for air."
After a string of doctors — a family doctor, an orthopedist, a neurologist — the final diagnosis came in August 2010: ALS. The diagnosis was devastating, but the timing couldn't have been better, the neurologist told him.
By the time Harada went in for his surgery in March 2011, he was using a cane, unable to walk to the end of the driveway for the mail without losing his breath or to climb the 15 stairs to tuck his children in at night.
He saw the trial as a way to smirk at the disease, to become part of the solution that might one day beat it back for other patients, even if it didn't do a thing for him: "I did the research, and I said to the doctors, 'Yeah, I'll be your guinea pig.'"
But what happened after his surgery no one had expected.
The 14 other patients involved in the trial to date have shown no improvement; four have died — three from complications of ALS, and the other from a heart-related issue, according to Neuralstem.
In contrast, Harada put aside his cane soon after the surgery. And he was again tucking his children into their beds.
Feldman is insistent: Don't read too much into Harada's turnaround. The number of patients is tiny, and Ted is an oddity among them.
Still, Harada's improvement, even if temporary, can't be ignored.
The researchers have used several tests to measure patients' outcomes, such as breathing capacity, the strength of their handgrip, and even the electrical impulses that flow through their muscles. There on these graphs is Harada, his dotted lines suddenly shooting upward after surgery.
In designing the clinical trial, "we were only aiming at stopping the disease," said Dr. Karl Johe, chairman and chief scientific officer of Neuralstem. "But this is a patient that has clearly improved."
Recently, Harada has begun to get winded again climbing the steps to his children's bedrooms. He and wife, Michelle, 39, a sixth-grade teacher, have explained to their children that he probably won't get better this time.
A six-hour procedure
Ed Tessaro was facedown, mostly draped in surgery blue in the crowded Emory operating room. It was 12:23 p.m. on July 20.
A stainless steel, crane-like contraption had been screwed into the cervical section of his spine. A steady beep-beep-beep of the monitors punctuated the hiss of a respirator. A digital camera recorded every movement for the FDA.
Standing just a few feet from Dr. Nicholas Boulis, who collaborated with Feldman on her research for seven years during his residency, Glass was ready with the spinal cord exposed.
It was 2:34 p.m. when Boulis asked for the cells.
For the next half hour, the vials were readied for the patented apparatus, on which an injection device slid along a guide to Tessaro's spinal cord. It would inject 100,000 cells for each of five stops precisely 4 millimeters apart.
The target was the ventral horn of the spinal cord, a tiny area associated with motor neurons.
At 3:06 p.m., the injection device slid into place. A needle extended, injecting deep into the spinal cord and, for two minutes, the stem cells were forced into the ventral horn.
At 3:29 p.m., the fifth and final injection began, and two minutes later, the relief was palpable. From her viewing spot just a few yards from Tessaro's neck, Feldman shifted on her feet and exhaled. The procedure, from start to finish, took a little more than six hours.
Technicians began to check recordings and run over the notes for the FDA. Boulis and the others began the process of removing the device and closing in the gaping hole in Tessaro's back.
Feldman transferred the digital recording of the process to a memory stick she could review back at the office. A copy would go to the FDA, too.
There will be many more months of data, continued animal tests and most likely, hundreds of pages of reports.
Even if this early stage is proved safe and the clinical trial continues, doctors must figure out whether these are the stem cells that work best in this therapy, and, if so, in what amounts and injected into which areas. There's the issue of the patients' bodies rejecting these foreign bodies, too.
"This is not a small molecule pill, and your patients go home and take the pill and you see them in your clinic in a few months," said Steve Perrin, CEO of ALS Therapy Development Institute, a Massachusetts-based nonprofit focused on finding a treatment or cure for ALS. "These are the challenges this trial and this technology have in front of (them). They're paving the road, because no one has been down this way before."
Friday, Tessaro was recuperating well at his home.
http://www.usatoday.com/news/health/story/2012-08-05/clinical-trial-fights-ALS/56791326/1
DETROIT – Sometimes she glares at the painting of Jesus in her dining room.
By Kimberly P. Mitchell, Detroit Free Press
Regis Kleiss, 28, of Royal Oak, Mich., is taking part in a clinical trial to combat amyotrophic lateral sclerosis, led by the University of Michigan.
EnlargeClose
By Kimberly P. Mitchell, Detroit Free Press
Regis Kleiss, 28, of Royal Oak, Mich., is taking part in a clinical trial to combat amyotrophic lateral sclerosis, led by the University of Michigan.
Sponsored Links"I just let it loose," said Mary Kleiss at her Royal Oak home. "I look at that picture and I say, 'You get down here and put on your boxing gloves and let's get this over with.' I am so damned angry."
Her son, Regis, was diagnosed 2½ years ago with Lou Gehrig's disease, formally known as amyotrophic lateral sclerosis, or ALS. It is, he writes, "as if God is torturing me."
The disease kills with swift and stunning efficiency — deadening its victims' peripheral nerves, withering muscles and, in a final assault, shutting down their ability to breathe. An estimated 30,000 people have the disease at any given time; 5,000 are diagnosed yearly. Most die within a few years. There is no cure.
The disease has reduced Regis Kleiss, 28, a formerly thick-bodied shot and discus thrower and captain of the high school track team, to a bony echo of himself.
Paralyzed except for some minor movement he can make with his head, he will spend his final days on a feeding tube, unable to hold his bassett hound, Riley, or hug his parents or his niece or even scratch his head. And the cruelest thing of all? ALS leaves its victims' minds intact.
"It's a miserable, damned disease," his mother said.
Now, a clinical trial overseen by the University of Michigan may provide hope. It's tentative and early. But when the rest of a person's life has been compressed to an expectancy of two to five years, it is hope, nonetheless.
The trial has been based in Atlanta since 2010, but Michigan has requested approval from the U.S. Food and Drug Administration to expand it and move it to Ann Arbor. It is cutting-edge and audacious work — the only ALS trial so far in which neural stem cells are injected directly into a patient's spinal cord. So far, 15 patients have undergone the procedure — two of them twice — as the FDA monitors its safety.
One patient showed a remarkable improvement, though Michigan's Dr. Eva Feldman, who heads the research, cautions not to read too much into that.
The trial involves injecting 500,000 to 1 million stem cells into the spine. The ancestry of the line of cells dates to the spinal cord of an aborted fetus in 2000.
Feldman and others theorize that these new cells act as nursemaids to damaged nerve cells, sending out repair signals, and somehow halting the progression of the disease.
The procedure worked in rats. It has been shown to be safe in pigs.
If the FDA approves the expansion of the human trial, patients will have access to an experimental treatment that not only might offer insight into a disease that kills an estimated 15 Americans a day, but also push back the battle lines against other neurodegenerative diseases, such as Parkinson's, Alzheimer's or Huntington's.
Last month, Feldman flew down with a team of Michigan staff for the 17th surgery in the trial, in anticipation that the trial might soon move to Ann Arbor. The trial has been at Emory University in Atlanta since it began.
Feldman is clear and she repeats this often: This part of the trial tests safety only. By design, it doesn't assess the efficacy of the treatment yet.
So the clinical trial patients so far — all from the Atlanta area — know the experimental stem cell therapy probably will not cure them. Still, they're empowered, knowing their participation might one day cure others, said Ed Tessaro, a retired Macy's executive.
The following morning, Tessaro, 66, lay on an operating room table at Emory's hospital, as doctors removed part of the bone in his spine and laid bare a pulsating, bright-white spinal cord for a second infusion of stem cells.
"It may kill us," Tessaro said of the disease, "but it's not going to defeat us before we die."
'The worst thing I could tell you'
It was 2008 when a single misstep and near-stumble during a half-marathon in Bangkok, Thailand, first worried Tessaro. It happened more than once. His muscles weakened, even as he stepped up his time at the gym.
Months later, a doctor delivered the news to him and his wife, Judy.
"She said, 'It's the worst thing I could tell you,'" Judy Tessaro recalled.
"'You have ALS, and you have two to four years to live,'" Ed Tessaro added.
Tessaro took stock. Life had been good, he decided.
Tessaro has been married for 43 years. He has a daughter and son, and is a grandfather to two little girls.
Now, every conversation, every gentle touch from his wife, the babbling of his grandbabies — his senses are in now in hyperdrive.
"In retrospect, I was living in analog. What I'm now living my life in is high-definition. I'm living my life fully, because I know I have less of it," Tessaro said.
When he heard about the clinical trial, Tessaro jumped at it.
"It's not like I can hope for a miraculous reversal of this disease — it's not coming," he said. "I don't think I have anything to lose and I can be part of something bigger. It's great therapy when you commit yourself to something bigger."
He became Patient No. 12 on April 13. Doctors slipped stem cells into the lower — or lumbar — section of his spine. The area that controls lower body movement, it was considered least risky because Tessaro was already losing the strength in his legs anyway.
Tessaro survived. In fact, he left the hospital days earlier than expected and felt better sooner than he expected.
So doctors decided — and the FDA approved — a second, riskier, surgery for Tessaro. This time, doctors would move to the upper — or cervical — portion of Tessaro's spine, the area in which the nerves are responsible for breathing.
Feldman calls this area "precious real estate," the stretch of spine where researchers say they believe the treatment may be most effective.
"Higher risk, but maybe higher reward," Tessaro said, shrugging. He was in the pre-operating room of Emory University Hospital, surrounded by family and overnight bags and medical tubes and equipment.
It was July 20.
In a stretch of hallway and an elevator ride away, a nondescript FedEx box was being delivered to Dr. Jonathan Glass, director of the ALS clinic at Emory. His hands were working quickly.
An unexpected result
Ted Harada is on Page 8 of the March Journal of Stem Cells, which published the first study announcing the preliminary results of the first 12 patients.
Harada is the anomaly. Like Tessaro did last month, Harada this month will undergo a second surgery. And like with Tessaro, it took some time to diagnose the mysterious weakening of Harada's body.
The former FedEx managing director, now 40, noticed he was getting winded in 2009 while playing Marco Polo in the family pool with his three children: "I'd go under water and come back up, and I was sucking for air."
After a string of doctors — a family doctor, an orthopedist, a neurologist — the final diagnosis came in August 2010: ALS. The diagnosis was devastating, but the timing couldn't have been better, the neurologist told him.
By the time Harada went in for his surgery in March 2011, he was using a cane, unable to walk to the end of the driveway for the mail without losing his breath or to climb the 15 stairs to tuck his children in at night.
He saw the trial as a way to smirk at the disease, to become part of the solution that might one day beat it back for other patients, even if it didn't do a thing for him: "I did the research, and I said to the doctors, 'Yeah, I'll be your guinea pig.'"
But what happened after his surgery no one had expected.
The 14 other patients involved in the trial to date have shown no improvement; four have died — three from complications of ALS, and the other from a heart-related issue, according to Neuralstem.
In contrast, Harada put aside his cane soon after the surgery. And he was again tucking his children into their beds.
Feldman is insistent: Don't read too much into Harada's turnaround. The number of patients is tiny, and Ted is an oddity among them.
Still, Harada's improvement, even if temporary, can't be ignored.
The researchers have used several tests to measure patients' outcomes, such as breathing capacity, the strength of their handgrip, and even the electrical impulses that flow through their muscles. There on these graphs is Harada, his dotted lines suddenly shooting upward after surgery.
In designing the clinical trial, "we were only aiming at stopping the disease," said Dr. Karl Johe, chairman and chief scientific officer of Neuralstem. "But this is a patient that has clearly improved."
Recently, Harada has begun to get winded again climbing the steps to his children's bedrooms. He and wife, Michelle, 39, a sixth-grade teacher, have explained to their children that he probably won't get better this time.
A six-hour procedure
Ed Tessaro was facedown, mostly draped in surgery blue in the crowded Emory operating room. It was 12:23 p.m. on July 20.
A stainless steel, crane-like contraption had been screwed into the cervical section of his spine. A steady beep-beep-beep of the monitors punctuated the hiss of a respirator. A digital camera recorded every movement for the FDA.
Standing just a few feet from Dr. Nicholas Boulis, who collaborated with Feldman on her research for seven years during his residency, Glass was ready with the spinal cord exposed.
It was 2:34 p.m. when Boulis asked for the cells.
For the next half hour, the vials were readied for the patented apparatus, on which an injection device slid along a guide to Tessaro's spinal cord. It would inject 100,000 cells for each of five stops precisely 4 millimeters apart.
The target was the ventral horn of the spinal cord, a tiny area associated with motor neurons.
At 3:06 p.m., the injection device slid into place. A needle extended, injecting deep into the spinal cord and, for two minutes, the stem cells were forced into the ventral horn.
At 3:29 p.m., the fifth and final injection began, and two minutes later, the relief was palpable. From her viewing spot just a few yards from Tessaro's neck, Feldman shifted on her feet and exhaled. The procedure, from start to finish, took a little more than six hours.
Technicians began to check recordings and run over the notes for the FDA. Boulis and the others began the process of removing the device and closing in the gaping hole in Tessaro's back.
Feldman transferred the digital recording of the process to a memory stick she could review back at the office. A copy would go to the FDA, too.
There will be many more months of data, continued animal tests and most likely, hundreds of pages of reports.
Even if this early stage is proved safe and the clinical trial continues, doctors must figure out whether these are the stem cells that work best in this therapy, and, if so, in what amounts and injected into which areas. There's the issue of the patients' bodies rejecting these foreign bodies, too.
"This is not a small molecule pill, and your patients go home and take the pill and you see them in your clinic in a few months," said Steve Perrin, CEO of ALS Therapy Development Institute, a Massachusetts-based nonprofit focused on finding a treatment or cure for ALS. "These are the challenges this trial and this technology have in front of (them). They're paving the road, because no one has been down this way before."
Friday, Tessaro was recuperating well at his home.