Note: This video was created in January 2020

Almost 18,000 Americans every year. Many of these people are unable to use their hands and arms and can’t do everyday tasks such as eating, grooming or drinking water without help.

Using physical therapy combined with a noninvasive method of stimulating nerve cells in the spinal cord, 91���� researchers helped six Seattle area participants regain some hand and arm mobility. That increased mobility lasted at least three to six months after treatment had ended. The research team Jan. 5 in the journal IEEE Transactions on Neural Systems and Rehabilitation Engineering.

“We use our hands for everything — eating, brushing our teeth, buttoning a shirt. Spinal cord injury patients rate regaining hand function as the absolute first priority for treatment. It is five to six times more important than anything else that they ask for help on,” said lead author , a 91���� senior postdoctoral researcher in electrical and computer engineering who completed this research as a doctoral student of rehabilitation medicine in the 91���� School of Medicine.

“At the beginning of our study,” Inanici said, “I didn’t expect such an immediate response starting from the very first stimulation session. As a rehabilitation physician, my experience was that there was always a limit to how much people would recover. But now it looks like that’s changing. It’s so rewarding to see these results.”

After a spinal cord injury, many patients do physical therapy to help them attempt to regain mobility. Recently, have shown that implanting a stimulator to deliver electric current to a damaged spinal cord could help paralyzed patients walk again.

The 91���� team, composed of researchers from the , combined stimulation with standard physical therapy exercises, but the stimulation doesn’t require surgery. Instead, it involves small patches that stick to a participant’s skin like a Band-Aid. These patches are placed around the injured area on the back of the neck where they deliver electrical pulses.

The researchers recruited six people with chronic spinal cord injuries. All participants had been injured for at least a year and a half. Some participants couldn’t wiggle their fingers or thumbs while others had some mobility at the beginning of the study.

To explore the viability of using the skin-surface stimulation method, the researchers designed a five-month training program. For the first month, the researchers monitored participants’ baseline limb movements each week. Then for the second month, the team put participants through intensive physical therapy training, three times a week for two hours at a time. For the third month, participants continued physical therapy training but with stimulation added.

“We turned on the device, but they continued doing the exact same exercises they did the previous month, progressing to slightly more difficult versions if they improved,” Inanici said.

For the last two months of the study, participants were divided into two categories: Participants with less severe injuries received another month of training alone and then a month of training plus stimulation. Patients with more severe injuries received the opposite — training and stimulation first, followed by only training second.

While some participants regained some hand function during training alone, all six saw improvements when stimulation was combined with training.

“Both people who had no hand movement at the beginning of the study started moving their hands again during stimulation, and were able to produce a measurable force between their fingers and thumb,” said senior author , a 91���� associate professor of electrical and computer engineering, rehabilitation medicine and physiology and biophysics. “That’s a dramatic change, to go from being completely paralyzed below the wrists down to moving your hands at will.”

In addition, some participants noticed other improvements, including a more normal heart rate and better regulation of body temperature and bladder function.

The team followed up with participants for up to six months after training and found that these improvements remained, despite no more stimulation.

“We think these stimulators bring the nerves that make your muscles contract very close to being active. They don’t actually cause the muscle to move, but they get it ready to move. It’s primed, like the sprinter at the start of a race,” said Moritz, who is also the co-director of the Center for Neurotechnology. “Then when someone with a spinal cord injury wants to move, the few connections that might have been spared around the injury are enough to cause those muscles to contract.”

The research is moving toward helping people in the clinic. The results of this study have already informed the design of that will be co-led by Moritz. One of the lead sites will be at the 91����.

“We’re seeing a common theme across universities — stimulating the spinal cord electrically is making people better,” said Moritz, who also holds the CJ and Elizabeth Hwang professorship in electrical and computer engineering. “But it does take motivation. The stimulator helps you do the exercises, and the exercises help you get stronger, but the improvements are incremental. Over time, however, they add up into something that’s really astounding.”

, a research scientist at the 91����; , a 91���� doctoral student in rehabilitation medicine; and , an associate professor of neurological surgery in the 91���� School of Medicine, are co-authors on this paper. This research was funded by the Center for Neurotechnology, the Washington State Spinal Cord Injury Consortium and the Christopher and Dana Reeve Foundation.

For more information, contact Inanici at finanici@uw.edu and Moritz at ctmoritz@uw.edu.

Grant number: EEC-1028725

Preclinical studies show that gene therapy can improve muscle strength in small- and large-animal models of a fatal congenital childhood disease know as X-linked myotubular myopathy.

The findings, appearing  as the in the January 22, 2014 issue of Science Translational Medicine, also demonstrate the feasibility of future clinical trials of gene therapy for this devastating disease.

Watch a by Brian Donohue on this study.

Researchers at the  91����,   in France, , and in Blacksburg, Va., conducted the study.

The study was based on seminal work on local and systemic administration in a mouse model of the disease performed by Anna Buj-Bello, at ��é��é�ٳ�Dz� since 2009. The 91����’s Martin K. Childers, working with Buj-Bello and Beggs groups, tested gene therapy using an engineered adenovirus vector, created by ��é��é�ٳ�Dz�. The vector carries a replacement MTM1 gene.

They used two animal models: mice with an engineered MTM1 mutation and dogs carrying a naturally occurring MTM1 gene mutation. These mutant animals appear very weak with shortened lifespans, similar to patients with myotubular myopathy.

The scientists found that both mice and dogs responded to a single intravascular injection of an adenovirus vector engineered for gene replacement therapy, produced at ��é��é�ٳ�Dz�. The treated animals had robust improvement in muscle strength, corrected muscle structure at the microscopic level, and prolonged life. No toxic or immune response was observed in the dogs.

These results demonstrate the efficacy of gene replacement therapy for myotubular myopathy in animal models and pave the way to a clinical trial in patients.

Children born with X-linked myotubular myopathy, which affects about 1 in 50,000 male births, have very weak skeletal muscles, causing them to appear floppy. They also have severe respiratory difficulties. Survival beyond birth requires intensive support, often including tube feeding and mechanical ventilation, but effective therapy is not available for patients, and most die in childhood.

Alan H. Beggs of Boston Children’s Hospital, co-senior author on the paper, has studied the mutated gene, known as MTM1, for many years and previously showed that replacing missing myotubularin protein effectively improved MTM muscles’ ability to contract.

“The implications of the pre-clinical findings are extraordinary for inherited muscular diseases,” said Childers, co-senior author on the paper, and co-principal investigator of the study with  Buj-Bello and  Beggs. “Two of our dogs treated with AAV gene therapy appear almost normal with little, if any, evidence, even microscopically, of disease caused by XLMTM.” Childers is a 91���� professor of rehabilitation medicine and a regenerative medicine researcher.

“These results are the culmination of four years of research and show how gene therapy is effective for this genetic muscle disease,” said Buj-Bello. “We finally can envision a clinical trial in patients. These are very promising results for future trials in humans. ”

Robert W. Grange, Virginia Tech associate professor of human nutrition, foods and exercise, and Virginia Tech graduate student Jon Doering provided expertise to demonstrate the dramatic rescue of muscle function in the treated dogs. “The functional improvement was truly remarkable,” said Grange. “It is both incredibly exciting and humbling to contribute to such a meaningful project – a true highlight of our careers.”

The study was funded by the Association Francaise contre les Myopathies, the Muscular Dystrophy Association, Myotubular Trust, Genopole d’Evry, INSERM, Region d’Alsace, the Anderson Family Foundation,  the Joshua Frase Foundation,  Where There’s a Will There’s a Cure Foundation, and the  Peter Khuri Fund for Myopathy Research. National Institute of Health grants P50 N5040828, R01 AR044345, R21 AR 064503, AR 0659750 and Ro1 HL115001 also funded the work.