• Health Watch: Stem Cell Trial

myfoxatlanta by Beth Galvin, October 18, 2010
View

A Georgia man battling Lou Gehrig's Disease or ALS, is gearing up for an experimental, risky surgery this week. On Wednesday, John Conley will become the seventh person in the U.S. to undergo a stem cell transplant for ALS.

When Conley was diagnosed with ALS in September of 2009, he said it was terrifying.

A few months later, Conley said he heard about research at Emory University where doctors were taking fetal stem cells derived from a fetus and directly injecting them into the spinal cord for the first time.

{showhide}

Conley said he signed up for because the procedure offered him hope.

If it's possible to be blessed, and cursed at the same time, Conley says that about sums up the last 13 months of his life.

At 58, Conley has a wife, two sons, and an incurable disease, known as ALS. The disease will gradually take away Conley's ability to walk and move his body.

Conley intends to allow Emory University surgeons to transplant hundreds of thousands of neural stem cells, derived from a fetus and grown in a lab, directly into his spinal cord. The procedure is high risk, and no promises.

Emory neurologist Dr. Jonathan Glass, who's heading up the stem cell study says the ultimate goal is to see if stem cells can actually slow down or stop the progression of ALS. First, researchers have to find out if the surgery and the stem cells are safe.

Conley, who gets massages to help him deal with the pain and spasms in his arms and legs, says in just the last month his leg muscles have markedly weakened.

"As ALS patients we only have hope, a renewed sense of hope," said Conley.

Conley says he knows the procedure may not help him win his battle, but, he hopes it will help others who follow in his footsteps.

Conley's surgery will take about four and half hours.

Dr. Glass says he knows this surgery is controversial because it involves the use of fetal stem cells. Controversy aside, the team feels there is tremendous potential to treat the fatal disease.

{/showhide}

• Human Neural Stem Cells Reverse Rat Stroke Brain Damage

Neuralstem has released a new report detailing positive results for stem cell treatments. Initial findings show that not only do implanted human spinal cord-derived stem cells survive, but also differentiate into neurons in rats brains affected by strokes. This finding could potentially provide new therapies for treating strokes.

{showhide}

Neuralstem stem cells survive and differentiate into neurons in rats with stroke

Neuralstem, Inc. announced that its spinal cord stem cells survived in rat brains affected by stroke and differentiated predominantly into neurons. The transplanted animals showed significant improvement in some motor skill and strength measurements. The study entitled, “Intracerebral Implantation of Adherent Human Neural Stem Cells To Reverse Motor Deficits in Chronic Stroke Rats,” was presented earlier today by senior study author, Dr. Shinn-Zong Lin, M.D., Ph.D., at the Stem Cells USA & Regenerative Medicine Conference, in Philadelphia, PA. Dr. Lin is a Professor of Neurosurgery and Vice Superintendent at China Medical University Hospital of Taiwan.

“This animal study shows the potential promise of this cell line in treating post-stroke symptoms,” Dr. Lin commented. “Four weeks after transplantation, the rats treated with Neuralstem’s cells showed significantly decreased asymmetric body swing, increased vertical movements and increased grip strength, compared with the control group.”

“Dr. Lin’s findings represent a significant milestone for Neuralstem. They are the first to show how our human spinal cord-derived stem cell product, NSI-566RSC, currently in a clinical trial for ALS, and which we expect to be in another clinical trial for spinal cord injury, also works in the stroke brain,” said Dr. Karl Johe, Ph.D., Neuralstem’s Chief Scientific Officer and Chairman of the Board of Directors. “Our proposed treatment for paralysis due to stroke will involve transplantation near the motor tracts close to the stroke lesion in the brain in order to promote regeneration and repair. While the trial protocol for ALS and chronic spinal cord injury involves transplantation into the spinal cord, and that for stroke will involve transplantation into the brain, we are nevertheless targeting the circuitry that controls motor function in each indication. We are developing clinical programs for stroke in both the U.S. and Taiwan, and hope to start our first trial in 2011.”

{/showhide}

• Neuralstem Files Spinal Cord IND Amid Stem Cell Hubbub

Neuralstem Inc.'s news that it filed an investigational new drug application for the first stem cell trial in chronic spinal cord injury came only two days after a federal judge's ruling overturned President Obama's stem cell policy, but that was merely "coincidence," said the firm's president and CEO Richard Garr.

{showhide}

“We’ve been working around the clock, and this just happened to be when we got it done,” he told BioWorld Today.

So it’s hard to say whether the 6.7 percent stock bump Wednesday was spurred by the latest IND filing or by the fact that Neuralstem, which works on fetal-derived neural stem cells rather than the more controversial human embryonic stem cells, isn’t likely to be at all affected by the late Monday ruling that claimed Obama’s March 2009 executive order to expand federal funding for hESC research was illegal. (See BioWorld Today, Aug. 25, 2010.)

Shares of Rockville, Md.-based Neuralstem (AMEX:CUR) gained 12 cents to close at $1.92.

While he doesn’t expect that ruling to stand, Garr also does not anticipate any political fallout to impede the agency’s review of Neuralstem’s IND. It shouldn’t have “any impact at all at the FDA on the ground level,” he said.

Besides, he pointed out, Neuralstem has “gone through [the IND process] once before.”

The firm gained clearance last year for a Phase I trial testing its spinal cord stem cells in amyotrophic lateral sclerosis patients, but was only allowed to move forward after a roughly nine-month clinical hold.

Other investigational stem cell treatments also have been hit with clinical holds, most notably Geron Corp., which waited several months for FDA clearance after filing an IND in 2008.

The agency lifted the hold in January (only a few days after Obama took the oath of offi ce), but Geron’s Phase I was stalled by another hold due to safety issues. The Menlo Park, Calif.-based fi rm was permitted earlier this month to resume the study of hESC therapy GRNOPC1 in subacute thoracic spinal cord injuries. (See BioWorld Today, Jan. 26, 2009, and Aug. 2, 2010.)

The FDA’s caution isn’t unusual for new therapeutic approaches, Garr said, but the good news is that the firm’s ALS trial is proceeding as planned.

To date, six patients have been transplanted with cells via direct injection into the gray matter of their spinal cords. Five of those have been reviewed by the study’s safety monitoring board and “are all doing well,” he added.

The proposed 16-patient Phase I trial in chronic spinal cord injuries – defined as patients with complete injuries for one to two years – will involve the same cells and same injection as in the ALS trial.

The plan is to start with eight patients who have thoracic injuries and, if data show the firm’s spinal stem cells are safe, to move on to patients with the riskier cervical spinal cord injuries, Garr said.

As in the ALS trial, safety is the primary endpoint, though Neuralstem hopes to measure some functional recovery as a secondary endpoint.

The company’s stem cells are not embryonic, but neither are they really adult stem cells. Its technology is designed to isolate CNS stem cells derived from fetal tissues and then expand each cell up to 60 doublings, or a billion billionfold, Garr said. “So one donated tissue can transplant over a million patients,” he explained.

But the cells are not immortal, so there’s less risk of expanding beyond the treatment area compared to hESCs. “And they have the best part of adult cells, in that we know what they will turn into,” he added.

Though there are no predictive animal models of chronic human spinal cord injury, transplantation of Neuralstem’s neural stem cells in a rat model of ischemiainduced spinal cord injury resulted in signifi cant motor recovery. Data from that study, published in the June 29, 2007, issue of Neuroscience, also indicated robust graft survival, extensive neuronal differentiation and integration of grafted cells into the host circuitry.

Pending smooth FDA clearance, Neuralstem hopes to start the spinal cord trial before the end of this year.

The company is funding its clinical programs on its own. As of June 30, it had cash, equivalents and marketable securities totaling $14 million, which included $9.3 million in proceeds from a June offering.

{/showhide}

• The Future of Stem Cell Research

On Monday an injunction regarding federal funding of embryonic stem cell research was issued that made  most of stem cell researchers very…confused. We look for clarity with Dr. Curt Civin, Director of the Center for Stem Cell Biology & Regenerative Medicine at the University of Maryland School of Medicine, Richard Garr, President and CEO of Neuralstem, and Dan Gincel, director of the Maryland Stem Cell Research Fund.

• Neuralstem wants trials on spinal patients

Biotech company Neuralstem Inc. said Wednesday it wants to test its stem cell treatment on patients with spinal cord injuries that have caused paralysis.  The Rockville-based company filed an application with the U.S. Food and Drug Administration seeking approval to start a new clinical trial, hopefully by the end of the year.

{showhide}

The spinal cord injury research would follow a current project that is testing the effectiveness of spinal cord stem cells on patients with amyotrophic lateral sclerosis, or Lou Gehrig’s disease.

“Since this is similar to the ALS trials, once we felt comfortable with the safety we felt it was time to move forward,” Neuralstem CEO and President Richard Garr said. In the proposed trial, researchers would inject spinal cord stem cells into 16 volunteers suffering from complete paralysis who had been injured up to two years beforehand.

Eight of the patients would have mid-back injuries with no motor or sensory function below the injury, while the second group would include patients with spinal injuries in the cervical area and no motor or sensory function below the injury.

With the ALS trial, the company directly injected stem cells into the “gray matter” of the spinal column using specially designed medical devices. In the proposed trial, the company would use a similar technique, but injections would be made at the site of the original injury.

Researchers hope the injections of healthy and functional spinal stem cells will replace or repair damaged and missing nerve cells at the injured areas.

Neuralstem’s spinal stem cell line is fetal-derived, coming from donated, eight-week-old tissue. Garr said that unlike embryonic stem cells that can be programmed to become other kinds of cells, Neuralstem’s fetal-derived cells are already “committed” to being central nervous cells. The trial would not be affected by Monday’s judicial decision that halted federal funding of stem cell trials using embryonic stem cells.

Neuralstem, a publicly traded company, would not use National Institutes of Health funding, and the U.S. District Court ruling did not affect private or state funding for stem cell trials.

Neuralstem said there are more than 10,000 new spinal cord injuries in the U.S. each year. A recent survey by the Christopher & Dana Reeve Foundation found there were approximately 840,000 people living with chronic spinal cord injury. According to the National Spinal Cord Injury Association, 85 percent of spinal cord injury patients who survive the first day are still alive 10 years later.

Shares of Neuralstem gained 12 cents, or 6.67 percent, Wednesday to close at $1.92. Shares had reached as high as $2.12 on the news of the clinical trial.

Neuralstem reported this month that it recorded a net loss of $4.9 million, or 12 cents a share, in the second quarter, compared to a net loss of $3.2 million, or 9 cents a share, in the corresponding quarter of 2009. The company attributed the change to the associated costs of moving its treatments from “the laboratory into the clinic.”

Neuralstem plans to conduct other trials on central nervous system diseases including ischemic spastic paraplegia and Huntington’s disease.

{/showhide}