Edwin Weeber, Ph.D., never thought he would be in a position to receive fan mail. Weeber, who is currently an Associate Professor at the University of Southern Florida (USF), has spent his graduate and post-graduate career conducting research on Angelman syndrome (AS). After 10 years of research and testing, he has discovered how to reverse the deficits of the disorder in mice.

Angelman syndrome, first discovered in 1965 by an English doctor, Harry Angelman, is a disorder that causes severe developmental delays, impedes speech and motor coordination. Other symptoms such as seizures and microcephaly affect about 80 percent of patients, according to the Angelman Syndrome Foundation Web site (www.angelman.org). Not evident at birth, AS is generally diagnosed after the age of 3 years. Relatively rare, AS affects between 1 in 15,000 and 1 in 30,000 people, and it is common for patients to exhibit some of the same earmarks as autism. These can include hand flapping and a short attention span. Although the two disorders can present similar symptoms, Weeber says that AS is considered more severe in nature.

Weeber started out as a graduate student studying microbiology at Baylor College of Medicine in Texas. Because his grandmother was suffering from Alzheimer's at the time, he was drawn to research of the brain, specifically learning and cognitive ability. Weeber began working with David Sweatt, Ph.D., who was conducting cognitive studies in his lab. While working in Sweatt's lab, Weeber became particularly interested in the hippocampus, a part of the brain that plays a role in memory. Down the hall from Sweatt's lab, another researcher was studying AS in mice models. "Angelman syndrome is a maternal imprinted disorder and there are no expressions of it in some parts of the brain - one of these is the hippocampus. So instead of studying random things in the hippocampus, I decided to study Angelman syndrome," says Weeber.

Prior to Weeber's studies, most of the research that had been conducted on AS had been genetic. The gene that carries the disorder was identified in 1997. Abnormal function in this gene, UBE3A, had been targeted as a possible cause for the disorder. UBE3A is a gene that is imprinted on the brain, meaning that the body knows what part of the gene is maternal and what part is paternal. "We get half of all of our genes from our mother and half from our father. The deletion or mutation of the mother's gene causes AS," says Weeber. Interested in the biomedical aspects of the disorder, he began studying enzymes and proteins in the brain that work with this gene. Weeber would make his groundbreaking discovery while working in his own lab at Vanderbilt University.

As he worked with his mice models from Baylor, Weeber discovered that he could reverse the effects of AS by regulating a particular enzyme, CaMKII. CaMKII is "an enzyme that is essential for learning and memory, as well as normal motor learning. We found that one of the biological abnormalities in AS mice was reduced CaMKII activity. It was known that reduced CaMKII activity results in neurological deficits. Thus, we concluded that regulating CaMKII in the mice may reverse their neurological deficits," says Weeber. When Weeber tested his theory by crossing mice with AS and mice with a mutation that caused them to retain their CaMKII activity, the resulting offspring had no AS symptoms. The seizure activity, mental retardation and problems with motor coordination all disappeared in the mice models. These results caused Weeber to conclude that the deletion or mutation of the maternal part of the UBE3A gene caused reduced CaMKII activity, resulting in AS.

Weeber says that when the activity of CaMKII enzyme is regulated, the deletion of the maternal part of the UBE3A gene is corrected. He adds that this enzyme is not produced until after the mice are born. This may also be the case in humans. Weeber says that this conclusion is an important when it comes to the treatment of AS. "This suggests that AS is not developmental in nature, but rather biochemcial. In other words, the brain appears to be wired correctly, but the change in CaMKII activity prevents the proper communication between the neurons in the areas of the brain where maternal UBE3A imprinting occurs."

Six months ago, Weeber, his wife and their son moved to Florida. The couple has since welcomed a new daughter to the family, and Weeber has taken the position as Associate Professor at USF. Weeber and his wife, who has a Ph.D. in neuroscience, feel that a move to USF is a natural progression because the school is known for its work in cognitive studies. At USF, Weeber will pursue therapeutic approaches for AS patients. The results found in Weeber's mice models were obtained through genetic engineering, and so this method is not applicable to humans. He says that one of the approaches for treating AS in humans could be a pharmacological one that would modulate CaMKII. Another possibility is adeno-associated virus (AAV). Weeber explains that this is a method for introducing foreign genes in neurons of the central nervous system. AAV can be used to either introduce CaMKII with the same mutation that was used to rescue the AS mice, or introduce a UBE3A gene that would take the place of the deleted or mutated maternal UBE3A gene. Weeber plans to begin researching the use of AAV to treat AS in the next six months.

While Weeber's discovery has many positive implications for AS patients, it could also be good news for people with autism. He says that while AS patients and autistic people look very different, there are genetic similarities. "Future research may in fact find a relationship between changes in UBE3A and autism," says Weeber. Other disorders having to do with cognitive function may also benefit from his research. For now, parents of AS children are celebrating Weeber's work. Terry Jo Bichell is a Visiting Scholar at Vanderbilt Kennedy Center for Research on Human Development and the mother of a nine-year-old boy with AS. Bichell took a position at Vanderbilt not long after Weeber's article was published. "I suddenly realized that concentrating on a cure for AS was not a pie-in-the sky day dream, but a real possibility," says Bichell. "Now it feels like the answer lies just beyond a flimsy curtain. It is almost in sight."

 

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Announcement of the Minocycline in the Treatment of Angelman Syndrome Clinical Trial (formerly C3)

 

The Foundation for Angelman Syndrome Therapeutics (FAST) is thrilled to report that the University of South Florida (USF) will begin to recruit participants for a new clinical trial led by Edwin Weeber, Ph.D. The Minocycline in the Treatment of Angelman Syndrome Clinical Trial will be conducted at the University of South Florida Health's Center for Advanced Health Care, 2 Tampa General Circle, Tampa, Florida 33606. A total of twenty-four patients will be randomly selected to participate in this open label trial to determine the efficacy of Minocycline as a treatment for Angelman Syndrome.

Complete information about the Minocycline in the Treatment of Angelman Syndrome Clinical Trial is posted on ClinicalTrials.gov. Once you have reviewed the study criteria, if you wish to participate you will need to follow the published link at the bottom of the ClinicalTrials.gov information page or visit http://www.weeberlab.com/clinical_trials.html and submit your contact information. If you have questions, or if you do not have internet access, please contact the study coordinator at 813.396.0672.

FAST would like to thank actor Colin Farrell, the Dwight Stuart Youth Fund, and the J Cox Family Foundation for granting FAST $24,000.00 in travel assistance funds to assist families that must travel to Tampa, Florida for the Minocycline in the Treatment of Angelman Syndrome Clinical Trial. The money will be available to families that request financial assistance and it will be paid out as reimbursements for documented lodging and transportation expenses that those families incur in connection with the trial, not to exceed $1,000.00 per family.

We hope that families who have the ability to travel to Tampa without reimbursement will decline to participate in the reimbursement program. If you are selected to participate in the Minocycline in the Treatment of Angelman Syndrome Clinical Trial and would like to participate in the reimbursement program, please visit the FAST Participant and Caregiver Reimbursement Policy.

In addition to travel assistance funds, FAST has secured reduced rate lodging at the Tampa Hyatt Regency and the Wyndham Tampa Westshore and discounted airfare on American Airlines for families participating in the clinical trial. For more information on reduced rate lodging and discounted airfare, please visit FAST's Reduced Lodging and Discounted Airfare information page.

The Board of Directors of the Foundation for Angelman Syndrome Therapeutics is enormously grateful to the community, our supporters and all of the supporters of the Vivint Gives Back Project for securing the funding for the Minocycline in the Treatment of Angelman Syndrome Clinical Trial. Taking scientific research from the lab to humans in one year's time is practically unheard of. We could not have done this without all of you!!!

                                                                                                                       -Fast

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HOLLYWOOD superstar Colin Farrell has revealed for the first time that his treasured son James is a special-needs child.

 

Four-year-old James was born with a rare condition that affects his speech and mobility - but Colin stresses: "There's no heart-break about it. I'm incredibly blessed to have him in my life."

Colin also tells how his close family were overjoyed when James recently took his first steps - just in time to celebrate his fourth birthday.

"He's worked so hard for four years and he took his first steps just six weeks ago," the doting father says.

"When he took them it was incredible, there wasn't a dry eye in the house," Colin tells the Sunday World.

The actor also reveals that nobody but closest family members have known the amazing courage that his boy has shown in the first four years of his life.

"James has a form of cerebral palsy called Angelman Syndrome," he says. "He has his own journey going on, has certain issues with speech, certain issues with motor skills. But he's an incredibly happy boy."

 

WHEN Colin Farrell proudly led the Irish team on to Croke Park for the Special Olympics four years ago, little did he know that within months he would become the parent of a special-needs child.

 

The light of his life four-year-old James, who was born with an intellectual disability, fills his family with joy every day.

Nobody but closest family members know about the extraordinary courage James has had to display for the last four years.

Today, speaking for the first time about his special boy, Colin talks about his pride in the son who has "enriched my life incredibly".

He adds: "There's no heartbreak about it, it's not a sad story. I'm incredibly blessed to have him in my life."

The Hollywood star and James's mother Kim Bordenave discovered that James had a rare condition called Angelman Syndrome when he was about seven months old.

 

Thrilled
And just six weeks ago, his loved ones were thrilled when the boy walked unaided for the first time.

"He took his first steps about six weeks ago and it was four years in the making. All the work is his - he's worked his arse off for four years. And when he took the steps it was incredible, there wasn't a dry eye in the house.

"He's broken that barrier and it's about building on that now. I think it's like any parent. What I want to do for my son is just to make sure that he has the opportunity to reach his own individual potential. And that he's happy as can be.

"And I'll do whatever I can do, stay in his way, get out of his way, to see that that's realised. That's what it's all about."

The irony is not lost on the actor that, months after becoming involved in the Special Olympics, he too would face the same challenges as the families he met that day.

"It's mad the way the world works. It's bizarre. I experienced the overwhelming effect of being around those athletes pretty much just before my son was born with special needs.

"James has a form of cerebral palsy called Angelman Syndrome," explained Colin. "He has his own journey going on, has certain issues with speech, certain issues with motor skills. But he's an incredibly happy boy.

"I have never once thought of him in my life as somebody with a disability. It goes back to special needs and what is a disability and what isn't. It's about who can contribute to society and who can't?

"With my son, the only time I'm reminded that there's something different about him - that he has some deviation of what is perceived to be normal - is when I see him with other four- year-olds.

"Then I go 'oh yeah' and it comes back to me. But from day one I felt individually that my boy, he's the way he's meant to be."

Farrell added that one of the characteristics of the condition that James has is breaking into bursts of laughter. "He's incredibly, incredibly happy - it's a bit mad, that happiness is one of the symptoms of the condition that he has. It really is.

"It's hilarious, he literally does go into outbreaks of laughter from time to time and I'd love to say for no apparent reason. But apparent is the keyword there because there's a reason in his head.

"He has enriched my life incredibly and I wouldn't have it any other way."

Wonderful
He paid tribute to James's mother and his ex-girlfriend Kim for being proactive in getting James the early intervention he needs.

"His mother has done a great job, exploring every avenue, being very hands-on and making his life as rich as possible. She's a wonderful girl." Since James was born in September 2003, his dad has been juggling a career in Hollywood - starring in movies such as Miami Vice, Phone Booth and Minority Report - with spending as much time as possible with his son.

He's brought James on frequent trips home to Dublin to meet his extended family. And James has even met Colin's new girlfriend, Irish student Muireann McDonnell.

As anyone who knows Farrell will know, he can find humour in almost any situation, as is evident when he speaks about initially sourcing therapies for James. "When they told me first he was going to have occupational therapy, I swear to God I thought 'he's a bit f***ing young to be asking him what he's going to do with his life'.

"Now he works his arse off with occupational therapy, speech therapy, physio, working on his motor skills."

"His speech is affected, he's four and he's not really talking yet but he makes the most delectable sound in the world. You couldn't get a sound as good from a garden of f***ing birds. But he's not speaking, which is very frustrating for him.

"A lot of my frustration comes from wondering how frustrated he is and at times he does get frustrated. He can't explain how he feels or what's going on or maybe he wants something and he can't tell you what he wants. We're working on that."

The actor guards his son's privacy vigorously but decided to speak to this journalist about James because of "speculation" about his health over the last year.

He also feels that "the time is right" given his involvement as global ambassador in the World Summer Games at Shanghai, China last week.

He explains: "I haven't agreed with some of the newspapers' stories, including the Sunday World, about my family life over the years but I decided to talk to you.

"I was very against bringing him into the public spectrum at all or into the media. I just wanted to keep that element of my life very separate and I know it's very sacred. But because questions are being asked in the last year and because I'm very involved in Special Olympics, I think it's just the right time for me to talk to you about the fact that my son has special needs.

"I didn't want people to think that I was embarrassed by it or that I was hiding it."

Colin said that his own family in Dublin have been hugely supportive of him and of James.

Colin's mother Rita has been closely involved in James's development, while his older sister Catherine, who lives in Los Angeles, is a hugely important part of his life.

"I never talked about it before because there was no reason to. But now, in some way, I'm representing an organisation and a movement that specifically deals with children and adults that have intellectual disabilities, "Colin says.

"And I was gifted with a son who in years to come could be competing for Ireland, who knows? If he does, he does, and if he doesn't, f***ing great, I don't give a shite either way. Whatever he wants to do with his life is the most important thing.

"I don't want to be getting up on my high horse but it would be nice if some people read this and were affected by it in a positive way. I don't think they need to hear about me necessarily and my son for enlightenment.

"But I think for people who have children with intellectual disabilities that me coming out and talking about it might be a small bit of solidarity and if that happens it would be good."

Tournament
Colin is on a high after travelling to the Special Olympics in Shanghai and meeting the Irish team, who arrived back to Dublin yesterday with several medals to their credit.

Almost 150 athletes travelled to the Chinese city for the tournament, which takes place every four years and was last held in Ireland.

This is Colin's second Special Olympics. He first became involved in Dublin "when I was at home and a pleasantly out-of-work actor" and was asked by US organisers, the Shriver family, if he would like to become involved.

"I'd never heard of it or been exposed to the idea but I just jumped at it, " says the 31-year-old.

"I'd no idea the impact it was going to have on the volunteers, the athletes, their parents.

"I swear to Jesus, unless me mind is completely melted, I seem to remember the country being a nicer place for those two or three weeks. It was classic."

Of his involvement in Shanghai, he said: "The celebrity aspect is just about garnering as much media exposure as possible for it.

"The bottom line though is that just to be there as a human being was amazing.

"There's an overwhelming positivity and joy and the athletes are so welcoming and all embracing."

He says he was always determined to spend time in the Irish camp once he got there and paid a surprise visit the night before the opening ceremony.

"When I arrived in Shanghai, they had these official receptions to go to. And I went to a couple of them, and they were grand but they were all very red tape. Myself and me mate were in Shanghai and we decided to find out where the Irish team was staying. We jumped in a taxi and popped down to the hotel. When we got there there was a bash going on for the athletes. They were in the function room with a lot of parents and a lot of trainers. And it was just f***ing bedlam!

"You know, it's such a f***ing cynical world. I worry when I talk about it, am I going to sound twee? Am I going to sound all loved up and stuff? But the bottom line is you do get loved up.

"That's what I meant about Ireland being a nicer place to be for those three or four weeks. The whole country came alive with this essence of hope, of inclusion and acceptance and tolerance, and competition in a healthy way. I got completely caught up in it. That night, when I went to the hotel to see the Irish team, it was just f***ing great.

"I could never love like some of the people I've met in my life, for example, who have Down Syndrome. Many of them are the most loving human beings in the world. Lacking in suspicion, tactile, sincere, really the most beautiful human beings. I look around every day and I see people who are incredibly functioning, fully functioning. And a lot of them are miserable bastards."

He explains that the Special Olympics is a year-round movement that changes the lives of hundreds of Irish people.

"It takes place for a few weeks every four years. In the lead up to the games, there's incredible competition within different countries but the thing is, it's an ongoing thing and there's a hell of a lot of work that goes into it.

Wisdom
"The culmination is obviously the opening ceremony and the games. It's the most incredible environment to be in because it really gives you a kick and knocks you out of yourself. It knocks me out of me own shite, the 'woe is me, I could be doing this or I could be doing that'. It allows me the wisdom that comes from a lot of these athletes, to live in the present.

"The families of the athletes I met in Shanghai were going 'ah Jaysus Colin thanks a million, fair play to you for coming'. You'd nearly be embarrassed because they're thanking you. You hear about the athletes being heroes and it's all plain f***ing true. I genuinely get more out of it than I give, I genuinely do."