Hope for the “Angels”
For families battling Angelman Syndrome, the small clinical trial at USF Health is a first step toward finding a treatment for the severe neurological disorder
For Peyton Elkins, 6, who has a rare neuro-genetic disorder called Angelman Syndrome (AS), every day is a challenge. She cannot walk without help. She can’t dress or feed herself. She can’t talk, so her parents cannot always tell what’s upsetting her when she cries.
“I have hope, because we can’t live any other way,” said Peyton’s mother Melissa Elkins, of Knoxville, TN. “Science is making big strides. I know there will be a cure one day, and maybe before that there will be some treatments to help her with her challenges.”
Peyton is one of 24 children nationwide selected to participate in a clinical trial at USF Health investigating whether off-label use of the FDA-approved antibiotic minocycline will help improve the symptoms of AS. Currently, there is no cure or treatment for the disorder, which affects about one in every 15,000 children.
Over the course of their enrollment in the 16-week single-arm, open label trial, each child undergoes a series of tests, blood work and behavioral evaluations. Families travel to Tampa, FL, three separate times as part of their commitment to the study, which is funded through a grant by the Foundation for Angelman Syndrome Therapeutics (FAST).
The drug being studied was tested first in mice genetically altered to have AS. Although the condition is caused by a single or inactive gene, it results in relatively widespread and severe developmental delays affecting motor function, thinking and behavior. Seizures are one of the most common and debilitating conditions affecting children with the syndrome.
“If minocycline does have an effect on sleep, on seizures, on cognitive ability, it will potentially give us more insight into what we need to be looking at in other therapeutics, so it could open the door to a lot of different treatments for these kids,” said trial principal investigator Edwin Weeber, PhD, chief scientific officer and a neuroscientist at the USF Health Byrd Alzheimer’s Institute.
Supported in part by FAST, Weeber heads one of a handful of laboratories nationwide probing the molecular mechanisms underlying AS in a mouse model for the disorder and exploring strategies that may rapidly yield effective treatments.
One promising approach has been to test the effectiveness of existing FDA-approved drugs in treating the cognitive, motor coordination and physiological impairment established in the AS mouse model. Minocycline, a drug traditionally used to treat bacterial infections, has minimal side effects, penetrates the brain and appears to work in a way that may counter the molecular defects observed in AS, Weeber said.
When Weeber’s team administered minocycline to AS mice, the treated mice performed nearly the same as typical mice on tests for motor coordination and their ability to learn and remember increased as well. The USF preclinical research helped fast track minocycline as a candidate for one of the few clinical trials for AS.
Peyton was diagnosed at age 9 months, when her seizures began. Her parents suspected something was not right a couple of months earlier when their baby had trouble holding up her head and sitting. But, the symptoms of AS can mimic other neuro-developmental disorders like cerebral palsy and autism, so a quick blood test is required for genetic confirmation of the syndrome.
Over the last few years, Peyton’s parents have done all they can to provide supportive care to improve their daughter’s quality of life – from physical, occupational and speech therapy to medications to ease seizures and sleep difficulties.
And, Melissa Elkins says, the family, which includes Peyton’s siblings Owen, 4, and Ella, 1, draws emotional support from the tight-knit community of families touched by AS. Many parents connect through online social networking sites like the one maintained by FAST.
While she realizes the small minocycline clinical trial is just a first step, Elkins is excited to be part the journey toward a treatment.
“When you have a baby, you have huge dreams for them. Then you get a diagnosis and those dreams are shattered. I’m hoping we can have those back,” Elkins said. “I continue to hope that my child Peyton can one day be as typical as my other two.”
Results from the minocycline trial, which ends in February, are expected in early 2013, Weeber said. “If we see positive effects in these children, it would lead to a larger clinical trial.
– Photos courtesy of Melissa Elkins. Photo of Dr. Weeber by Eric Younghans/USF Health Communications
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