Day 3 at Neuroscience 2013: Spotlight on Experimental Autism Treatments

Date: 
November 12, 2013
Researchers discuss early findings on diverse experimental treatments – medicines, stem cell therapy, brain stimulation and more


This week’s autism presentations at Neuroscience 2013 include reports on the early promise of a broad variety of autism treatments. The findings are preliminary and involve small human studies or testing with various animal models of autism. As such, these therapies are at the earliest stages of development.

“At this year's meeting of the Society for Neuroscience, we're starting to see recent genetic and neurobiological advances in autism research being translated into experimental treatments,” comments Paul Wang, Autism Speaks vice president for medical research. “This is very encouraging as drug development is a long and difficult process. We will need a lot of ‘shots on goal’ to achieve our aim of improving symptoms and quality of life.”

In brief, here are some of the promising early findings being discussed this week. (Click on the hyperlinked subheads to read the scientific abstracts.)

Propranolol may improve social and reasoning skills in some persons with autism
Researchers at the University of Missouri-Columbia reported the preliminary results of a small trial testing how a single dose of the beta-blocker drug propranolol affected social and reasoning skills in teens and adults affected by autism. Propranolol is used to treat high blood pressure and as a short-term treatment for acute anxiety. For example, someone might take a dose to calm the voice and hands before a stressful event such as public speaking or performance. 

Twenty persons with autism participated in study, including one woman. The participants ranged in age from 15 to 31, and none had intellectual disability. In a first experimental trial, they received one dose (40 mg) of propranolol. In another trial, they received a placebo, or dummy pill. 

After one hour, a researcher engaged each participant in a one-on-one conversation and rated social skills such as staying on topic. asking appropriate questions and facing the researcher. In addition, the investigators asked the participants to memorize lists of words and solve anagrams. (For example, finding the word “BRICK” in “IRBCK.”) After the initial round of testing, those who received the dummy pill received the propranolol and vice versa before a second round of tests.

Those who took propranolol scored better overall than did those who received the placebo. The researchers were particularly struck by improvements in nonverbal behavior such as leaning or turning one’s body toward a person during conversation. They also noted that participants who had greater variability in their heart rates at the start of the experiments benefited most from propranolol. This biosign, or symptom, might help select which individuals with autism might benefit from such a treatment, they suggest.

Certain benzodiazepine drugs reverse autism behaviors in mouse model
Sung Han and colleagues at the University of Washington, Seattle, found that low doses of certain benzodiazepine drugs completely reversed autism-like behaviors in a mouse model of autism. But other types of benzodiazepine drugs worsened the animals’ social avoidance. Benzodiazepines include such familiar psychoactive drugs as Valium and Ambien.

Further, the researchers showed that the positive or negative effect of a particular benzodiazepine depended on which subunit of a particular brain receptor (GABA-A) it targeted. These receptors are naturally activated by GABA, a chemical brain messenger (neurotransmitter) that helps calm, or inhibit, brain activity. Recent research has suggested that an overabundance of excitatory over inhibitory brain messages may be behind autism’s core symptoms.

Ambien (generic name zolpidem) was one of the benzodiazepine drugs that worsened the mice’s autism-like behaviors. An experimental compound dubbed L-838,417 restored the mice’s social behavior and intellectual abilities to normal levels. However, very precise dosing was needed to achieve these benefits. The findings may help pinpoint a molecular target for medicines that can relieve autism’s core symptoms.

Relieving intellectual disability in autism mouse model
Around two-thirds of individuals with autism have some degree of intellectual disabilities. A similar pattern is seen in the BTBR mouse model of autism. Ronald Seese and his colleagues at the University of California-Irvine found that the research drug 2-Methyl-6-(phenylethynyl) pyridine (MPEP) normalized both learning and brain cell connectivity in the mice with both autism and impaired memory. Importantly, MPEP enhances the activity of a brain protein (ERK 1/2) associated with learning. (It does so by targeting the mGluR5 brain cell receptor.) As such this mouse study suggests that other medicines that target ERK 1/2 may have promise in relieving the intellectual disabilities associated with autism.

Injections of adult stem cells reduce autism behaviors in mouse model
Sung Ji Ha and her colleagues at Seoul National University College of Medicine relieved autism behaviors in a mouse model of autism with injections of human adipose-derived stem cells (hASCs). This type of stem cell is derived from fatty tissue such as that removed during liposuction treatment. It is also known to have an immune-suppressing, or anti-inflammatory, effect. The researchers based their experiment on the growing body of research showing that many individuals with autism have immune dysfunction and on the promising results of stem cell therapy in treating other brain disorders.

The researchers worked with a mouse model of autism that has increased repetitive behaviors and reduced social interaction. They injected the stem cells into the ventricals, or open spaces, of the brains of newborn mouse pups. One month later, the stem-cell treated mice had reduced repetitive behaviors as measured by how much they compulsively groomed themselves. They also socialized more freely with other mice. The findings suggest that stem cell therapy might be a promising new avenue for autism treatment development.

Long-term oxytocin impairs animals’ ability to produce the hormone
And in cautionary news, researchers from the University of California-Davis report that administering oxytocin to prairie voles over the long term impairs the animals’ ability to make the so-called “social hormone” on their own. The findings are of great interest to the autism community because early short-term trials of oxytocin nasal spray have shown improvements in social and verbal skills in individuals with autism. The new findings suggest that long-term treatment with the hormone may have unwanted side effects.