spinal cord injury, embryonic stem cells, paralysis, pain …

By LizaAVILA

SAN FRANCISCO Researchers have successfully transplanted healthy human cells into mice with spinal cord injuries, bringing the world one step closer to easing the chronic pain and incontinence suffered by people with paralysis.

The research team did not focus on restoring the rodents ability to walk; rather, it helped remedy these two other debilitating side effects of spinal cord injury.

If successful in humans, thefindingscould someday ease the lives of those with these distressing conditions, said Dr. Arnold Kriegstein, co-senior author of the study and director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UC San Francisco. The research was published in Thursdays issue of the journal Cell Stem Cell.

This is a very important step, Kriegstein said. The treated animals improved in pain relief and bladder function.The research offers the promising potential of using a new therapeutic approach cell therapy to repair damaged neural tissue, showing that new cells can be integrated into an injured spinal cord.

A similar approach also has helped mice with epilepsy and Parkinsons disease.

More than aquarter of a million Americans live with spinal cord injuries, and 17,000 new cases occur each year, according to the National Spinal Cord Injury Statistical Center. More than half of those people go on to develop chronic pain in their limbs, called neuropathy. And nearly all develop bladder problems, which can result in kidney damage.

The spinal cord is the major highway for nerve cells to relay information between the brain and the rest of the body. When the spinal cord is injured, tears and inflammation harm surrounding cells.

The field has been very focused on restoring patients ability to walk, perhaps because thats often their most visible impairment, study co-authorLinda Noble-Haeusslein, a professor of physical therapy and rehabilitation at UCSF, said in a statement.

But a recent study showing that patients complained of pain and loss of bladder control more than paralysis suggested that we had really missed the boat as a field, she said. It caused us to dramatically shift what we do in the lab.

The cells used in the study, called neurons, were grown from human embryonic stem cells the bodys building blocks, capable of generating more than1,000 different types of adult cells.

They arent just any garden-variety neuron. These cells have the ability to inhibit, rather than excite, the neural network of the spine. Thats important because the pain and loss of bladder control are believed to be caused by overactivated neural circuits.

The healthy body keeps this excitable circuitry under control.But inflammation caused by a spinal cord injury causes a loss of this control.

The UCSF team grew the replacement cells in a South San Francisco biotech lab ofNeurona Therapeutics, founded by study co-authorCory Nicholasand Kriegstein, UCSFprofessor of developmental and stem cell biology. The company hopes to mass-produce these cells for use in future clinical trials.

They injected the young human cells into the spines of mice about two weeks afterinjury. They targeted the thoracic region about halfway up the spinal cord because thats a common site of injury for humans.But they were careful not to inject the young cells directly into the injured areas because that is a toxic place full of inflammation.

Remarkably, over the next six months the human cells matured, migrated toward the site of the injury and made connections with the spinal cords of the mice.

Compared to untreated mice, the treated rodents showed significantly less hypersensitivity to touch and painful stimuli and reduced abnormal scratching. Treated mice also had improved bladder function and produced more normal, voluntary patterns of urination in their cages.

A different research team is focusing on a fix for paralysis. This necessitatesa different strategy, requiring treatment with stem cell-derived neurons whose job it is to conduct electrical impulses down the spine. And these cells may face a more daunting environment if injected directly into injured areas.

The first trial by Geron Corp. stalled in late 2011, mostly because of financial concerns. But a Fremont-based biotech company calledAsterias Biotherapeutics, a subsidiary of BioTime, bought Gerons intellectual property and is continuing the research. It recently received approval fromthe U.S. Food and Drug Administration for a safety and early trial of the cells for treating spinal cord injury.

Meanwhile, the UCSF team is working to replicate their findings of improved bladder control and chronic pain. And they seek to learn the best time to inject the cells. Funders for the research included the National Institutes of Health and the California Institute of Regenerative Medicine.

The team is hoping to scale up their production of their specialized cells with the goal of entering human trials, after proving to the FDA that their effort is safe.

We are eager to move in that direction as quickly as we can, Kriegstein said.

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