Sunday, April 20, 2008

Williams family deals with autism

With freckles across his nose, Matthew Williams looks a little like a child, but he is growing into a young man. For Matthew's family, that is another step in their journey with autism.

Matthew, 15-year-old son of Byron and Wendy Williams, has Landau Kleffher Syndrome and is classified as having a form of autism. A feature of LKS is the gradual or sudden loss of the ability to understand and use spoken language. Children with LKS have abnormal electrical brain waves on an EEG, a recording of the brain's electric activity.

LKS occurs most frequently in normally developing children between ages 3 and 7. For no apparent reason, understanding what is said to them becomes difficult. Intelligence appears to be unaffected.

Until about 24 months, Wendy Williams said her son developed normally.

"Matthew was a happy, social, outgoing baby," she said. "He met milestones on time or early. He crawled at six months and walked at 9 1/2 months. He was talking, had a pretty big vocabulary and said small sentences by the time he was 2 years old."

After he turned 2, she noticed changes in her son.

"Matthew started not sleeping, having laughing spells, was hyper and would only eat a small variety of foods," Wendy said. "Then at around 3, we went to a hospital in Chicago and found out Matthew was having seizure activity in his brain when he slept. This led us to his doctor in Mobile who diagnosed him with LKS."

That diagnosis led to taking medications.

"We started him on medications and at 4 he said the letter 'E.' Wendy said. "This was the first thing he had said since he was 2 years old. He started saying more words but his vocabulary was limited.

"We went through years of trying different medicines some okay some worse. Then around age 12, I told the doctor stop everything but seizure medicine. He became more social, behavior improved and his learning capabilities increased."

Adolescence brought more seizures, which was frightening.

"During adolescence he had his first physical seizure," said Wendy. "That is a terrifying experience no parent wants. To see your child turn blue in a second, stop breathing and twitching is frightening. Not knowing when he might have one is frightening because it could be life threatening. On the other hand you can't be so scared you don't let them do things they love doing."

The causes of LKS aren't known, but Wendy believes immunizations played a role.

"We believe his disorder was brought on by immunizations because as a baby he was normal in every way," she said. "Then at 22 months he received his MMR shot then another shot within a month. Within a month of his last shot he quit talking."

Whatever the cause, they have a positive attitude about a child Wendy describes as amazing.

"Matthew has a great memory," she said. "Ironically his favorite animal is an elephant; they say they never forget anything.

"Matthew loves cartoons and can repeat them word for word and sound by sound. He loves fishing with his Dad. He likes to go to the zoo, swimming, jumping on the trampoline, riding the four-wheeler, playing with his sister and cousins - typical kid stuff."

While he is typical in many ways, Matthew has challenges.

"Matthew is behind academically," she said. "That is one reason I decided to home school. Unfortunately, our school system doesn't have enough teachers educated in teaching children with autism.

"Matthew needs one-on-one instruction to learn properly. He has done well since we began home schooling. It was the right decision because he is an intelligent child; he just has problems understanding things and expressing himself."

The Williams have a 13-year-old daughter, Amber, and a 23-month-old son, Nicholas, too.

"Matthew watches out for Nicholas, but he doesn't want him touching his stuff or going in his room," said Wendy. "He plays with Amber and enjoys hanging around her friends when they come over. He also likes being around his cousins when they do things he likes to do."

The Williams think about Matthew's future.

"One of my concerns is Matthew being able to take care of himself with as little help as possible when he grows up," Wendy said. "He takes care of his grooming needs; he knows to take his medicine, and he can cook some things and does chores."

She wants society to have compassion for kids like Matthew.

"He functions like me and you he just likes to be by himself a lot and doesn't like people messing with his stuff," she said. "He is shy in public and makes noises when he is excited, frustrated or nervous. In many ways, he is a normal 15-year-old and in other ways, he is childlike.

"I wish people would understand children with autism are like you and me. They don't have a disease, they will not hurt you and you won't catch anything from them."

Wendy said it's hard to see the reactions her son gets.

"No parent wants to see or hear someone laughing, staring and making fun of their child for speaking or acting differently," she said. "It hurts and it makes you mad because you know he is just like anyone else's child - just a little more special.

"The next time you see a special needs person smile, say hello. A little understanding goes a long way."

Wendy said Matthew is a blessing.

"God does not make mistakes. We are lucky to have a child as special as Matthew," she said. "We love him with all our hearts and if you gave him a chance, you would too. Matthew has changed our lives forever; we miss out on some things but this is his life not ours."

She knows what Matthew might say if he could.

"If Matthew could ask for himself and for other special needs children, he would say, 'Open your minds and hearts with understanding ... because we are just like you. We just function a little differently.'"

Friday, April 11, 2008

Drosophila Drug Screen For Fragile X Syndrome Finds Promising Compounds And Potential Drug Targets

Scientists using a new drug screening method in Drosophila (fruit flies), have identified several drugs and small molecules that reverse the features of fragile X syndrome -- a frequent form of mental retardation and one of the leading known causes of autism. The discovery sets the stage for developing new treatments for fragile X syndrome.

The results of the research by lead scientist Stephen Warren, PhD, chair of the Department of Human Genetics at Emory University School of Medicine, are published online in the journal Nature Chemical Biology.

Dr. Warren led an international group of scientists that discovered the FMR1 gene responsible for fragile X syndrome in 1991. Fragile X syndrome is caused by the functional loss of the fragile X mental retardation protein (FMRP). Currently there is no effective drug therapy for fragile X syndrome, and previously no assays had been developed to screen drug candidates for the disorder.

During the past 17 years, intense efforts from many laboratories have uncovered the fundamental basis for fragile X syndrome. Scientists believe FMRP affects learning and memory through regulation of protein synthesis at synapses in the brain. One leading view, proposed by Dr. Warren and colleagues, suggests that over stimulation of neurons by the neurotransmitter glutamate is partly responsible for the brain dysfunction resulting from the loss of FMRP.

In their current experiment, Emory scientists used a Drosophila model lacking the FMR1 gene. These fruit flies have abnormalities in brain architecture and behavior that parallel abnormalities in the human form of fragile X syndrome. When FMR1-deficient fly embryos were fed food containing increased levels of glutamate, they died during development, which is consistent with the theory that the loss of FMR1 results in excess glutamate signaling.

The scientists placed the FMR1-deficient fly embryos in thousands of tiny wells containing food with glutamate. In addition, each well contained one compound from a library of 2,000 drugs and small molecules. Using this screening method, the scientists uncovered nine molecules that reversed the lethal effects of glutamate.

The three top identified compounds were known activators of GABA, a neural pathway already known to inhibit the effects of glutamate. In the study, GABA reversed all the features of fragile X syndrome in the fruit flies, including deficits in the brain's primary learning center and behavioral deficits. The screening also identified other neural pathways that may have a parallel role in fragile X syndrome and could be targets for drug therapy.

"Our discovery of glutamate toxicity in the Drosophila model of fragile X syndrome allowed us to develop this new screen for potential drug targets," notes Dr. Warren. "We believe this is the first chemical genetic screen for fragile X syndrome, and it highlights the general potential of Drosophila screens for drug development.

"Most importantly, it identifies several small molecules that significantly reverse multiple abnormal characteristics of FMR1 deficiency. It also reveals additional pathways and relevant drug targets. These findings open the door to development of effective new therapies for fragile X syndrome."

First author of the article was Shuang Chang, postdoctoral student in Emory's Department of Human Genetics. Other authors included Steven M. Bray and Peng Jin from Emory, Zigang Li from the University of Chicago and Daniela C. Zarnescu from the University of Arizona.

The research was supported by the National Institutes of Health, the Fragile X Research Foundation, and the Colonial Oaks Foundation.

Dr. Warren is chair of the scientific advisory board for Seaside Therapeutics, which is developing drugs for fragile X syndrome.