Skin Cells to Brain Cells? Yes and it may help MS Patients

Stem Cell Advance Could Aid in Multiple Sclerosis - WSJ.com
The Wall Street Journal by GAUTAM NAIK


Scientists have converted human skin cells into brain cells and used them to treat mice with myelin disorders, a family of diseases that includes multiple sclerosis.

The research, reported Thursday, marks another promising advance for a technique known as cell reprogramming. The approach returns mature cells to an embryonic-like state, and then transforms them into various types of fresh, healthy tissue that could be used to treat diseases.

Multiple sclerosis is the most common myelin disorder. It strikes when the body’s own immune system attacks myelin, the coating around nerve fibers. That disrupts communication between cells and can cause problems related to muscle movement, balance and vision.

In the latest study, the reprogramming technique “led to the re-myelination of the complete nervous system” of diseased animals, improving their symptoms and prolonging their life, said Steven Goldman, lead author of the report and a neurologist at University of Rochester Medical Center in Rochester, N.Y.

The findings appear in the journal Cell Stem Cell.

Myelin is made in cells known as oligodendrocytes. Those, in turn, are the offspring of oligodendrocyte progenitor cells, or OPCs.

One way to tackle a malady like multiple sclerosis is to transplant healthy, lab-made OPCs into the diseased brain, which could restore the lost myelin and reverse the damage from the disease.

Dr. Goldman’s team first reprogrammed human skin cells into embryonic-like stem cells. Then they identified the cascade of chemical signals used by the body to turn embryonic cells into OPCs—and replicated that process in a lab dish.

It was hard to do, mainly because OPCs form very late in the body’s development, via a multistage and complex process. It took the researchers six years to decipher the signals and to produce and purify enough OPCs that would yield sufficient myelin.

The OPCs were transplanted into mice with leukodystrophy, a hereditary condition that rendered them incapable of producing myelin. (Each year, thousands of children are born in the U.S. with some form of leukodystrophy.)

In the experiment, untreated mice displayed the typical symptoms of myelin-loss as they grew older: They developed tremors, lost their sense of balance and died prematurely, often from seizures.

The treated group initially also developed tremors and other symptoms. But once the transplanted cells began to produce sufficient myelin—it took four months—their symptoms improved and they no longer died of seizures.

Dr. Goldman said he hopes to start human trials using the cell-transplantation approach in 2015.

Write to Gautam Naik at gautam.naik@wsj.com

A version of this article appeared February 8, 2013, on page A6 in the U.S. edition of The Wall Street Journal, with the headline: Research Offers New Hope for Multiple Sclerosis.


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Inexpensive card-sized device runs 50 blood tests in seconds

Inexpensive card-sized device runs 50 blood tests in seconds
By Ben Coxworth

December 31, 2012

Ordinarily, when medical clinicians are conducting blood tests, it’s a somewhat elaborate affair. A full vial of blood must be drawn, individual portions of which are then loaded into large, expensive machines such as mass spectrometers. The results are usually quite accurate, but they’re not instantaneous, and require the services of trained personnel in a well-equipped lab. That may be about to change, however. Scientists from Houston’s Methodist Hospital Research Institute and MD Anderson Cancer Center have created a credit card-sized gadget, that can instantly check a single drop of blood for up to 50 different substances – and it costs about US$10.

Developed by a team led by Dr. Lidong Qin, the device is known as a volumetric bar-chart chip – or the V-chip, for short.

It consists of two thin sheets of glass, with a series of 50 tiny wells sandwiched between them. Each of those wells can contain different types of antibodies, selected for their tendency to bind to specific proteins. All of the wells also contain an enzyme known as catalase, along with hydrogen peroxide, and a dye. A sample drop of blood or other bodily fluid is placed in another well, at one end of the V-chip.

Initially, all of the wells are isolated from one another. When the two glass plates are slid against one another, however, the wells are linked by one long continuous zig-zagging microfluidic channel. The sample fluid flows along that channel, going through each of the wells as it does so.

When the antibodies in any one of the wells react with the targeted substance – such as insulin, or a specific drug or virus – the catalase is activated, which in turn splits the hydrogen peroxide into water and oxygen gas. That gas pushes the dye up a column linked to the well, where it can be seen by the user. The higher the dye goes in that column, the greater the amount of the substance in the sample. Viewed as a whole, the V-chip appears as a bar chart, indicating the relative amounts of the various targeted substances.

Although lab tests would likely still be the way to go for the most accurate, detailed results possible, the V-chip could prove very useful in places like developing nations, where laboratories are inaccessible or non-existent. It could also find use in emergency rooms or ambulances, where caregivers need to detect the presence of specific drugs or poisons as fast as possible.

Qin and his team are now working on making the V-chip more user-friendly. A paper on the research was recently published in the journal Nature Communications, which also features a video on the device.



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A bionic eye may be closer

The Quest to Create a Bionic Eye Gets Clearer
By SHIRLEY S. WANG

Have scientists finally created a bionic eye? The quest to develop a device that will give some blind people vision again, a retinal prosthesis, has been challenging. Shirley Wang joins Lunch Break with the latest on the research. Photo: Second Sight.

Restoring sight to the blind has proved particularly challenging for scientists, but a new technology combining an eye implant and video-camera-enabled glasses may soon be available in the U.S.

Researchers have been pursuing the development of such a bionic eye for decades, in some cases spending hundreds of millions of dollars to tackle engineering challenges. One device designed to help people with a rare eye condition is awaiting U.S. regulatory approval. It is known as Argus II, made by Second Sight Medical Products Inc. of Sylmar, Calif. Other researchers, including at the Massachusetts Institute of Technology and Stanford University, continue to work on what they believe are even more sophisticated versions.


Second Sight's product uses what is known as a retinal prosthesis that bypasses the dead or damaged cells in the eye needed to detect light. Instead, the device reroutes visual data via the implant to parts of the eye that still work. Like other similar devices under development, it uses a video camera embedded in a pair of eyeglasses to collect visual input in the form of light and transmit it to the implant as an electrical signal.

If Argus II is approved by the Food and Drug Administration, it would be the first retinal prosthesis to hit the market in the U.S. The device is already available in Europe.

The patients most likely to benefit from these devices are those with retinitis pigmentosa, a rare disease that damages and kills the cells in the retina—a tissue layer at the back of the eye—that process light. For people with the condition, their vision grows increasingly blurry until they eventually can't see at all. Some 100,000 patients in the U.S. have the condition.

Another group of patients who may find such technology useful, scientists say, is those with severe macular degeneration. This is an age-related disease that damages the part of the eye that perceives fine detail, according to the National Eye Institute. The various retinal prostheses under development all use video cameras to send light information to chip implants. Most of them use the data to trigger electrodes in the chip to stimulate pixels of light on the retina, which are then processed normally by the brain as images.

The technology tested to date lets the wearer primarily see in black and white. It is most useful for seeing sharp contrasts, such as the painted white line of a crosswalk on a dark road. But scientists hope that they can improve the detail to eventually enable color vision in its wearers.

Barbara Campbell, a 59-year-old vocational rehabilitation counselor, has had virtually no sight since her 40s. She had the Argus II implanted in her left eye in 2009 after hearing about the device through her work at the New York state Commission for the Blind and Visually Handicapped.

Though she was told the device was experimental, Ms. Campbell thought, "anything I gain will be a plus," she said.

Ms. Campbell had a five-hour surgery at New York-Presbyterian Hospital and two months later was fitted for the video glasses. Returning to her apartment, she could see that the light fixtures in the hallway of her building were different from how she remembered they used to be.

While her vision is still limited to discerning large objects such as furniture, she said, she can now see the pole at her bus stop instead of having to locate people standing nearby. When she goes to the theater, she can follow the actors on stage, though she cannot see their facial expressions.

"It's very exciting and it's very cool," Ms. Campbell said. "I felt that my brain now had to become used to using vision again," she said.

Some 50 patients, including Ms. Campbell, have been implanted with the Argus II, with two-thirds of them experiencing benefits. The patients who respond the best can read large letters a few inches tall. Patients report the biggest gains are in improved orientation and mobility, said Robert Greenberg, Second Sight's CEO, who also is a medical doctor.

Designing a bionic eye has been much more difficult than developing other types of aids, such as a cochlear implant for hearing, say scientists. For one thing, visual information is two-dimensional—both horizontal and vertical coordinates must be sent to the brain—while sound waves needed for hearing are one-dimensional.

Another challenge is protecting the implant in the eye, since it essentially has to sit in a bath of organic liquid. "It's like taking your television and throwing it in the ocean and expecting it to work," said Dr. Greenberg. Scientists have spent time working out how to manufacture tiny, airtight boxes that can shield implants when they are in the eye.

A big obstacle has been figuring out how to adequately capture and stimulate enough pixels of light on the retina to produce a clear image. Normal vision is based on more than one hundred million receptors in each eye, but it is impossible to squeeze that many electrodes into a tiny device that has to lay on the retina, said John Wyatt, a professor in the department of electrical engineering at MIT who has been working on a retinal prosthesis since 1988.

Second Sight's Argus II contains 60 electrodes, but some other scientists say that for a retinal prosthesis to be truly useful to patients, hundreds are needed. "In theory, you'd like to have more electrodes, but not if it means an implant that doesn't survive more than a few months" because the device is too bulky and unstable to stay in place in the eye, Dr. Greenberg said. "That was the trade-off we made."

Instead, the company is working to create better video cameras and software, which are external to the eye and easily updated, to better enhance and interpret the information sent to the implant, he said.

Dr. Wyatt and his group at MIT are developing a bionic eye that will contain between 256 and 400 electrodes. They are currently working on their fifth version. Earlier models have been implanted successfully in Yucatán miniature pigs and temporarily in six humans. They are planning to form a company to commercialize their technology.

At Stanford University, ophthalmology professor Daniel Palanker's group has taken a different approach to the problem. Instead of using electrodes, his team developed rows of tiny "photovoltaic" pixels (like solar panels), powered by the pulsed light from the video goggles, which are implanted under the retina. These implants convert light into electric current that stimulates local retinal neurons, which then send signals to the brain, meaning no wires are necessary to stimulate the retina.

Using this technology, Dr. Palanker expects to be able to fit enough light-powered panels to stimulate 5,000 pixels in a space similar to what the other retinal prostheses use. The device is currently being tested in rats and is expected to begin a human trial in a year or two, he said.

Write to Shirley S. Wang at shirley.wang@wsj.com

A version of this article appeared January 29, 2013, on page D1 in the U.S. edition of The Wall Street Journal, with the headline: The Quest To Create A Bionic Eye Gets Clearer.


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Rehab for Cancer Survivors, its about time

The informed Patient
Prescribing a New Kind of Rehab for Cancer Survivors
By LAURA LANDRO


Patients who undergo cardiac-bypass or joint-replacement surgery routinely are given specific guidance to the exercises and therapies they will need to return to their everyday activities and to prevent complications or relapse.

For cancer patients, the story is very different.

After undergoing often harsh and debilitating treatments, there is often little help for their return to normal life.

Now, an increasing number of hospitals are offering programs to provide cancer patients with comprehensive rehabilitation services, amid mounting evidence that these can help speed recovery, shorten hospital stays and improve quality of life.

Rehabilitation services are "an absolutely essential part of cancer care," says Dan McKellar, chairman of the Commission on Cancer. Last year the nonprofit standards-setting group, overseen by the American College of Surgeons, began requiring cancer programs to offer rehabilitation services to be eligible for accreditation. Major cancer centers are taking steps to better coordinate rehabilitation after treatment. And Medicare and most insurance companies are covering such services.

Doctors who specialize in rehabilitation medicine can evaluate patients for fatigue, pain, anemia and decreased endurance that result from chemotherapy, radiation and surgery. They can then prescribe physical and occupational therapy, as well as treatment for sleep problems, depression and cognitive impairment. Dietitians help with nutrition, as cancer can change the way the body uses food and patients often lose their appetite from treatment. Some institutions offer massage and yoga.

More than a third of the nation's 12.6 million cancer survivors had physical or mental health problems that put their overall health in jeopardy and had a negative impact on their quality of life, according to a recent study of federal health data funded by the National Cancer Institute. While patients may get emotional help from friends, family and support groups, physical problems may get scant attention once they are no longer in the care of oncologists and surgeons.

"When cancer patients are diagnosed, everyone sits down to look at the case, decide what to do and convey that plan to the patient, but the same sort of process doesn't happen for survivors of the treatment," says Kathryn Weaver, lead author of the study and an assistant professor at Wake Forest Baptist Medical Center in Winston-Salem, N.C. Patients, she adds, may feel their physical problems are "the new normal" and may not ask their doctors for help. And even though most hospitals have rehabilitation services, there may not be a formal program to identify cancer-patient needs or coordinate a care plan among different therapists.

One model being adopted by hospitals, including Johns Hopkins in Baltimore, M.D. and Bon Secours St. Francis Health System in Greenville, S.C., is called STAR, for Survivorship Training and Rehab. It uses specially trained teams of caregivers, coordinated by navigators such as nurses, to help patients with physical and emotional issues, as well as any other concerns that arise.

In 2011, Dan Yarborough, a 67-year-old attorney, had two stem cell transplants within months of each other and high-dose chemotherapy to treat multiple myeloma, a form of blood cancer, at Bon Secours. The treatments left him weak and fatigued, with pain and numbness in his feet that threw off his balance and left him unable to walk steadily and unable to stop himself from falling if he tripped. Golf and travel, favorite pastimes, were out of the question, and he was worried about being able to argue his cases standing in court.

While hospitalized for his second transplant, a nurse navigator from the hospital's STAR program set him up with regular physical therapy appointments and nutrition counseling. Staffers helped him establish goals such as improving his ability to get in and out of his SUV, and worked with his doctors to change medications that were linked to his foot problems.

The program was "incredibly valuable," Mr. Yarborough says, giving him back the stamina to return to work. He is following up with a recommended exercise program at a medical fitness facility owned by the hospital where his exercise plan is overseen by a STAR-certified physiologist for a $30-per-month fee.

The Bon Secours STAR team also deals with specific issues such as helping head and neck cancer patients restore normal functions of swallowing, speech and movement after treatment. "In a lot of hospitals you will see these patients fall through the cracks after surgery, so their cancer is gone but they can't turn their neck to drive a car," says Lori McKitrick, a speech therapist who oversees the program. "We are doing a great job saving people's lives but we have to help them live their lives too."

Julie Silver, an assistant professor at Harvard Medical School and expert in rehabilitation medicine, developed STAR after her own treatment for breast cancer, which she says left her too sick to care for her family or return to work. Her oncologist suggested she rest and try to heal on her own, but "it left me thinking there has to be a better way," Dr. Silver says. "Every cancer survivor should have the opportunity to heal as well as possible and function at optimal level whether their cancer is cured, in remission or they live with cancer as a chronic disease," Dr. Silver says.

She started a company, Oncology Rehab Partners, which helps health systems and hospitals create their own STAR programs for many types of cancer. STAR certification is used by insurance companies in reimbursement decisions. The program costs a typical hospital about $25,000 to launch with an annual fee of $10,000 for continuing education and recertification, Dr. Silver says.

Michelle Houle, 45, has been participating in the STAR program at Bon Secours since she was diagnosed with breast cancer in 2010. After chemotherapy, a bilateral mastectomy and radiation, Ms. Houle, on long-term disability from her job as a food company shelf manager, says she felt "about 90 years old." Nurse navigators at the hospital set her up with a specialist to help prevent lymphedema, a painful swelling of the lymph nodes and a common side effect of breast surgery, and she began a physical therapy regimen.

Ms. Houle suffered a recurrence in 2011 and is now on another chemotherapy regimen, but keeps up her exercises at the hospital's medical fitness facility. She is slowly returning to activities like gardening and housework. The rehabilitation program provides "a base to keep you going," she says, "and there is always someone to talk to if I'm feeling side effects."

Signature Healthcare in Brockton, Mass, which includes Brockton Hospital and 150 employed doctors, treats local cancer patients and those who have had treatment at major centers in Boston, then return home for follow-up with difficult physical aftereffects. Last week, it launched its own STAR program after 23 staffers went through six months of training and received STAR certification. "These needs have been unmet for such a long period of time, and they are very excited to be able to offer this enhanced level of service" says Linda McAlear, the program's coordinator.

A version of this article appeared January 29, 2013, on page D1 in the U.S. edition of The Wall Street Journal, with the headline: Prescribing a New Kind of Rehab for Cancer Survivors.


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