Stem cell studies a long way from autism answers

A recent post in the Nature blog Spoonful of Medicine talked about how the Sutter Neuroscience Institute in Sacramento has started recruiting kids for a clinical trial on an experimental stem cell therapy for autism. The author, Kathleen Raven (@sci2mrow), reported that the research team there hopes their study answers questions about a disease with "few, largely ineffective treatments."

The California team will recruit 30 autistic children between ages 2 and 7 who have cord blood banked at a Cord Blood Registry near the institute. That’s because the Sacramento study will use each child’s own stem cells as treatment, and because cord blood is a stem cell source that avoids the debate surrounding embryonic stem cells. Other autism stem cell trials underway include a Chinese study using cells donated from other children’s cord blood, and a Mexican study where stem cells will be harvested from each child’s fatty tissue.

We asked Alan Percy, M.D., professor in the UAB School of Medicine’s Division of Pediatric Neurology, and Fred Biasini, Ph.D., associate professor in the Department of Psychology, for their take on the studies. Their short answer was that the three studies are unlikely to soon answer the question of whether or not stem cells can treat autism. The Chinese study is complete but has not published any papers and the Mexican study is still recruiting.

Percy says the most important, eventual achievement of the California trial may be to prove with rigorous science that such treatments do not work. The problem, he says, is that some parents are so hungry for answers that they will pursue therapies even If the science is not there. In many cases they leave the U.S. to gain access to treatments in places with much less rigorous patient protection laws in place. Percy sees many pursue this course but no evidence of treatment success.

While the techniques used in the Sutter study have a very small chance of working, Percy says, they may provide insights into better ways to use a patient’s own stem cells in future attempts to create treatments.
The idea that stem cells might improve an autistic child’s ability to speak is based on the theory that the disease has some autoimmune roots. Immune cells in the brain mistakenly attack brain cells to cause inflammation. The hope is that injected stem cells would recognize the ‘autoimmune’ cells as foreigand clean them out. The problem, says Percy, is that such cells would have to enter the central nervous system, an obstacle that has stymied many promising treatments.

UAB is one of the 14 study sites within the Autism and Developmental Disabilities Monitoring (ADDM) Network, says Biasini. Funded by the Centers for Disease Control, the network had been working in recent years to determine how common autism is and how that changes over time and by region. So far, they have determined that about 1 in 88 children have a confirmed autism spectrum disorder.

Biasini also mentioned the following as samples of key UAB autism research:

• An effort led by Biasini and Maria Hopkins, Ph.D., an assistant professor of psychology in the UAB College of Arts and Sciences, seeks to understand how the ability to interpret facial expressions, or not, affects social skills in children with autism with the goal of improving social interactions.
• Work by Sarah O’Kelley, Ph.D., assistant professor in UAB Department of Psychiatry and Behavioral Neurobiology, who is studying social interventions such as the organizing of social skills groups, to see which are most effective in improving social skills in children and adolescents with ASD.
• Kristi Menear, Ph.D., associate professor in the Department of Human Studies within the UAB College of Arts and Sciences, is looking at the impact of exercise on cognitive and social development in adolescents with an ASD.  Exercise has been shown to reduce the impact of various mental and physical health conditions, and her study will look at whether the effect is there in autism as well.
• Irena Bukelis, a psychiatry resident at UAB, is examining the types of medications prescribed to children suspected of having an ASD, which typically include antipsychotic, ADHD and antidepressant drugs. The work will help researchers understand the medication-related issues faced by families as they seek to address a child’s cognitive, social and language challenges, often before they receive an official diagnosis of ASD.

For more information on the state of autism research, Biasini recommends a new and thorough review of current work just published by the Interagency Autism Coordinating Committee (IACC), organized under the auspices of the U.S. Department of Health & Human Services.  Another strong source of information, research resources and registries is Autism Speaks.

Tornado/hurricane shelter and the 9/11 anniversary

When I heard my first tornado siren this spring, it reminded me of the experience of living through Sept. 11, 2001, in New York City, a tragedy now two weeks from its eleventh anniversary.

My wife and I lived in a small apartment on the Upper East Side of Manhattan. That morning we saw a seemingly endless caravan of fire engines rushing downtown as the news flashed the first images of planes hitting the World Trade Center. We spent the day huddled without power, and breathed in dust from the fallen towers as it blew in through our windows.

The same career that had taken me to Manhattan carried me south late last year to UAB. I arrived about six months after the April 27, 2011, tornadoes that took so many lives in Alabama, and we often felt echoes of the storms' aftermath. Our son played his first Alabama baseball in Cahaba Heights near neighborhoods that had been stripped of trees, and where many homes had been recently repaired.



On March 2 this year, we sat up at 3:30 a.m. listening to the storm sirens echo across Vestavia Hills, me getting pings on my phone from UAB’s B-ALERT system. I remember feeling that same nervous dread I felt on 9/11.

My family’s current plan is to huddle in an internal closet should a tornado hit, with our options improving if we have more notice. We would have the kids put on their baseball helmets, but of course getting them into a storm shelter would be the best thing.

For that reason, I was fascinated to learn about the work of Uday Vaidya, Ph.D., professor within the UAB Department of Materials Science & Engineering, who is designing a new high-tech tornado shelter.  The panels making up the shelter just passed the tornado threat test from the National Storm Shelter Association (NSSA).

In a feat of materials science, Vaidya and his team used thermoplastic and fiberglass resins, foams and fibers to make panels that are stronger in some ways than the steel in many current shelters. Some of the same materials are used in the latest armored vehicles, and in the UAB team's case they're recycled from discarded oil rig pipe insulation that would otherwise be piling up in landfills.

In the NSSA test, 15-pound two-by-fours fired from a pressure cannon were unable to penetrate the panels in a dozen attempts. The wooden missiles hit the panels at 100 mph, the speed at which projectiles typically exit a tornado funnel spinning at more than 200 mph. Such a storm would rate EF5 on the Enhanced Fujita scale and be capable of leveling well-built homes. Take a look at our recent article and the included video for details.

The successful NSSA test represents a first step toward commercial availability, which the team hopes to achieve by the 2013 tornado season. They started the effort after Hurricane Katrina, and have been working even more urgently since last year's tornadoes. The NSSA test was on Aug.1, and the team just filed its patent applications on Aug. 24.

For more information on tornadoes, please see the National Oceanic and Atmospheric Administration site or its storm prediction center. To follow the design project, look up the UAB spin-off company led by Vaidya: Innovative Composite Solutions.

Guest post: stronger laws may mean less childhood obesity

A New York Times piece earlier this month reported on a study that found Body Mass Index (BMI) increases were smaller for students from the 5th to the 8th grade in states where strong laws govern what foods can be sold at schools outside of the federal meal program. These “competitive foods” include products sold in vending machines, at cafeteria ala carte lines and in school stores.  

The study, published on Aug. 13 in the journal Pediatrics, was titled “Weight Status among Adolescent in States that Govern Food Nutrition Content.”  Its findings establish an interesting correlation for public health advocates like me who have been looking for evidence to support a more global approach to our fight against the childhood obesity epidemic. The Times piece links to the Centers for Disease Control, which reports that about one fifth of American children are obese.

Among the strengths of the study is that it objectively rates 40 states on how strong and specific their laws are concerning the types of foods sold in schools. The research team also used data gathered on the actual, competing foods obtained rather than relying on self- reports from parents or children. The study also appropriately stopped short of stating that stricter states laws were the cause of the lower BMI increase because this type of study could not answer that question. But the correlation seen in their data does raise the possibility that stronger state laws could help.

BMI overall increased from 5th to 8th grade for the 6,000 students in this study, but for the kids in the states that had stronger laws, the BMI gain was not as great. This is hard to interpret for individual children because I have taken care of some adolescents who have medical conditions, or are underweight and need to gain. From a population perspective in a country with an epidemic underway, however, any change that can slow weight gain is a plus. For many children, especially in Alabama, laws that promote the slowing of BMI increases should be welcomed.

Speaking of Alabama, I am left to wonder how we did in this study. The authors did not disclose how each state ranked in terms of their scale of strong to weak. There were data license restrictions and they could not report this. They did mention that, at the start of the study in 2003, 70 percent of the students in states with strong laws lived in the South.

Alabama was given a “B+” grade in 2006 by the Center for Science in the Public Interest in regards to policies for competitive foods in school.  In 2009 the “F as in Fat Reports” funded by the Robert Wood Johnson Foundation reported that Alabama has a nutrition standard for school meals and snacks that exceeds government standards, nutritional standards for competitive foods and limited access to such competitive foods. That said, Alabama, along with several Southern states, continues to rank among the highest in terms of childhood obesity levels. The research presented in Pediatrics does suggest that stronger laws could help slow the obesity epidemic facing our children.

Guest Blogger: Stephanie Wallace, M.D., is an assistant professor in the UAB Department of Pediatrics who is active in UAB's Pediatric Weight Management Program.

Cost of stigma, here and abroad

AIDS came home for my family when my mother, a nurse practitioner who cared for HIV-positive patients in the late 1980s, had a needle-stick accident. After injecting medication into a patient, she had pricked herself with the same needle, potentially exposing herself to the virus. She dodged the bullet, but many of her patients, well-loved members of our community, did not.

For this reason, I read with interest a recent feature article in the journal Science. It detailed how AIDS has shifted over 31 years from a disease of white, economically secure gay men on the coasts to one of poor African Americans – gay and straight – in the South, home to 43 percent of the country’s HIV-infected people. The virus has followed a trail of poverty south.

In an interview following publication of the article, Michael S. Saag, M.D., director of the UAB Center for AIDS Research, talked about how one contributor to the spread of HIV in the Deep South is fear. AIDS symptoms are ignored or hidden more in the African-American community due to cultural differences with respect to tolerance of homosexuality, says Saag. Being gay is taboo in both African-American and white communities, he says, but is especially so among African Americans, and even more so among African-American churchgoers.

Saag also recently recommended that I cover a study published this week in the journal PLOS Medicine by his colleague, Janet Turan, Ph.D., associate professor in the Department of Health Care Organization and Policy at the UAB School of Public Health. Her study found that fear, this time of being labeled HIV-positive, was contributing to the spread of HIV in Kenya.

Fear of stigma was strong enough to keep mothers in one Kenyan province from having babies in health-care facilities because their communities had come to see such places as mostly for HIV-positive women, according to Turan’s study. Specifically, her team found a close link between HIV-related stigma and the fact that just 44.2 percent of mothers in Nyanza Province deliver their babies in facilities with skilled caregivers.

Professional help greatly increases the chances that any mother, HIV-positive or not, will survive childbirth, which takes the lives of more than 250,000 women in developing nations each year. In Nyanza, a region where one in five pregnant women is HIV-positive, skilled care during pregnancy and birth also increases the likelihood that those infected will receive antiretroviral drugs that prevent the passing of HIV from mother to child. Sadly, past studies in the region have reported that being labeled HIV-positive links women with promiscuity in the eyes of their families, often causing them to be abused by male partners, who are less likely to visit clinics or be tested for HIV themselves.

Many Kenyans think the region’s clinics are the best place to give birth for women with pregnancy complications, but women who do choose to use the clinics—over home births with traditional attendants—run the risk of being labeled HIV-positive. The stigma is so strong that many people have adopted a low opinion of anyone living with HIV, and not without cost. The study found that women with such opinions were about half as likely to deliver their baby in a health facility as those without them.

Government campaigns seeking to halt mother-to-child transmission of HIV may actually be part of the problem, Turan says. By urging HIV-positive mothers to give birth at clinics, the campaigns may be inadvertently promoting the idea that childbirth there is mainly for women who are HIV-positive. Public health messages need to be changed to stress that skilled care is a lifesaver for all women, says Turan.

For more information about the AIDS epidemic today at home or in Africa, or about UAB’s related efforts, see the sites for the UAB Center for AIDS Research, UAB’s 1917 Clinic for patients with HIV/AIDS, or the United Nation’s 2015 Millennium Development Goals, which include lowering the maternal death rate in developing countries by 75 percent.

About the Blogger

Greg Williams @gregscience @themixuab is research editor within Media Relations at the University of Alabama at Birmingham.

Heart disease, depression and night lights

Sleep is proving more elusive than ever for Americans, even as evidence mounts that lost sleep puts us at greater risk for everything from depression to diabetes to heart disease.

According a recent Wall Street Journal piece, a National Sleep Foundation survey found that 51 percent of people aged 19 to 29 years, and 43 percent of 30-somethings, say they rarely or never get a good night’s sleep on weekdays.

In my case, quality sleep is often interrupted as massive Alabama thunderstorms or bad dreams chase my 5-year-old into our bed. In the case of nightmares, one thing we've tried is tucking our son back into bed in the gentle glow of his turtle-shaped night light.

Then I read this article in Science News by Janet Raloff (@jarsciencenews) that says exposing him to light when he’s sleeping could be bad for his mind and body.

I ran the idea of night light as health threat by Karen Gamble, Ph.D., assistant professor in the Behavioral Neurobiology Division of the Department of Psychiatry in the UAB School of Medicine. It turns out that the connections between nightly light exposure, circadian rhythm and disease risk are hot research areas, and that she is recruiting for a related study in shift-working nurses right now.

“When environmental and bodily rhythms are out of sync, circadian misalignment results, which can contribute to increased risk of cardiometabolic problems and cancer, as well as to mental disorders,” says Gamble.

Life on earth evolved for eons based on a rhythm: day and night, light and dark, wake and sleep, eat and fast. Researchers in recent years even have discovered a genetic feedback loop in our cells that operates in roughly 24-hour cycles, with links to hundreds of gene pathways, many of which regulate how our cells process energy. In other words, it looks like we are wired at the genetic level to sleep at night, and to wake up and eat during the day -- and that bucking those patterns may have consequences.

“Think about the airlines and other industries that rely on light for their nightly function,” says Gamble. “Lighting at night in most hospitals is very bright for patients, as well as the workers. It will be interesting to see the results of future studies that finally tell us whether or not hospitals brightly lit 24/7 slow patient recovery.”

And what about hospital workers? Gamble has begun a study looking at the health of shift-work nurses, who are “greatly exposed” to the effects of light at night and to chaotic sleeping patterns. Most hospitals employ a “standard” schedule of several consecutive 12-hour shifts followed by several days off.  Because 97 percent of nurses choose to go back to sleeping at night on their days off, her team is particularly interested in how these nurses choose to switch back and forth and how these strategies affect their health and mood.

Experiments will measure rhythms of activity, hormones and body function to determine how sleep patterns affect the nurses’ degree of circadian misalignment. The research team also will collect data on chronic light exposure over this period to assess how light at “night” affects adaptation to shift work.

Gamble says those interested in circadian genetic clocks, nightlights and sleep patterns should take a look at this Howard Hughes Medical Institute webcast series or the Circadian Rhythm Laboratory site by the University of South Carolina. Also, check out the science behind using special glasses to block out the blue light portion of your artificial lighting before bed, which may raise levels of the sleep hormone melatonin.


About the blogger

Greg Williams @gregscience @themixuab is research editor within Media Relations at the University of Alabama at Birmingham.

Chemotherapy pump drives 3D drug design

Cancer treatment often fails because of p-glycoprotein, which pumps chemotherapies out of cancer cells before the drugs can kill them. Nearby healthy cells use the same protein to pump out thousands of toxins, so you can’t just shut it down with a drug.

What we need are chemotherapies that can evade the pump or drugs that clog it up only in cancer cells to keep chemo in them longer. But how can you begin to tell which molecules might be capable of such feats?

Crystallography and X-ray diffraction reveal the 3-D structural maps of disease-related proteins as a starting point for drug design. Researchers gain insight into an envisioned drug’s ideal shape from the map of its protein target, like making a key from the lock it must fit into.

Stephen Aller, Ph.D., assistant professor in the Department of Pharmacology and Toxicology within the UAB School of Medicine, first solved the crystal structure of p-glycoprotein in 2009, earning him a cover story in the journal Science and national recognition. Aller sat down with The Mix to share his amazing computer animation of the protein’s structure and take us on a photo tour of his lab.


Chemo pump drives 3D drug design from uabnews on Vimeo.

Show notes

0:33 Multi-drug resistance is driven by several mechanisms, but treatment efflux via drug pumps is a major contributor to treatment failure.

1:12 Molecular map-making is possible because proteins happen to form orderly, repeating stacks called crystals when you coax them close together in a solution.

1:38 X-ray diffraction involves bouncing X-rays off of the growing crystal, and then rebuilding the reflections into a map of the protein’s structure using with computer algorithms.

2:10 Virtual drugs based on the maps can be tested in computer simulations before you incur the great cost of making the would-be drug in the real world.

2:45 Protection provided by p-glycoprotein in healthy cells goes awry in cancer cells, which make more of it to pump out chemotherapies.

3:18 Screening efforts are under way to find chemotherapies that can evade the drug pump in cancer cells.

3:48 Molecular structure, revealed by crystallography, has enabled Aller’s team to fine-tune drug candidates that could one day block the pump in cancer cells.

5:26 Aller shares his favorite resources for those interested in crystallography, including the RCSB Protein Data Bank, where most of world's protein structures are stored, and PIMOL, a player for making animations like his. 

About the blogger

Greg Williams @gregscience @themixuab is research editor within Media Relations at the University of Alabama at Birmingham.

Olympic material

Olympic performances are becoming ever more glorious thanks to advanced materials used in the latest vaulting poles, rowing shells and bathing suits, according to a recent Scientific American podcast covering a Nature Materials series. One more reason for me to watch the games for 30 hours this weekend.

We asked Uday Vaidya, Ph.D., professor in the UAB Department of Materials Science and Engineering about the affect of space-age materials on sports and lives beyond the Olympics.

In London, advanced materials are on display in events from archery and tennis to swimming, rowing and cycling. All feature tools, vehicles or clothing made of materials that offer improved strength, stiffness, impact-resistance and, in the case of swimwear, nanomaterial-enabled water resistance.

In tennis, carbon fiber and titanium rackets offer more flexibility and resilience, with materials recipes customized to accommodate each player’s swing, says Vaidya. Safety helmets and vests used by boxers and equestrians are lighter but offer greater protection thanks to high-tech foams and fabrics woven into new architectures. Take a look at this NBC video on the design of safety helmets and this Washington Post piece on how swimsuit tech has changed the pace at which world records are set. 

Beyond the Olympics, materials are poised to change daily life, says Vaidya. New car panels promise better protection than traditional carbon steel, but weigh a third as much. The recently launched Boeing Dreamliner is made of carbon fibers that reduce the aircraft’s fuel consumption while making possible more comfortable seating and bigger windows.

Buildings and bridges soon will be built of advanced concrete with embedded sensors that can detect impending structural failure or earthquakes and “self-heal” to extend the structure’s lifespan. UAB-related materials projects include components for next-generation tourniquets and body armor that promise to save soldiers’ lives and noise-dampening panels for high-school band-practice rooms and, someday, entire city blocks. We also can look forward to smart homes with roofs that better harness energy and cars that come with autopilot.

On the medical front, materials engineers are designing artificial joints that last decades and smart stents that more efficiently keep open once-clogged arteries. Scaffolds hold surgical repairs in place and then dissolve, while artificial cartilage soon will speed recovery from injury. More kinds of artificial organs are on the way as well.

Those with a serious interest in materials engineering should look up the Materials Research Society, The Minerals, Metals & Materials Society and Tghe Society for the Advancement of Material and Process Engineerin, Vaidya says. He also recommends the magazines Advanced Materials and Processes, Composites Technology and Composites Manufacturing.