January 2001 was a happy time for Dan and Tina Carson, of Havre de Grace. It's the month their second child, and first son, was born.
Mark Carson was welcomed not only by his dad and mom, but also by Dan and Tina's first born, daughter Sarah. The young family seemed off to a happy and healthy future.
It was about four years later when Dan, a Realtor by profession and noted decoy carver, and Tina, a registered nurse, began to notice something wasn't quite right with their son.
It didn't seem terrible. He was experiencing general weakness. He would fall easily. He had trouble climbing stairs. Also, his calves seemed swollen, but it would turn out it wasn't because they were especially muscular.
The family physician was stumped and the Carsons were sent to Sinai Hospital in Baltimore to see a specialist, Dan Carson recalls. The doctor, noting the symptom of swollen calves, ran a blood test and came back with a diagnosis: Duchenne's muscular dystrophy. Dan Carson had never heard of it.
"I was thinking good, we know what it is. Just prescribe some pills and we'll treat it," he said in a recent interview.
Duchenne's, the doctor clarified, has no treatment. Its victims have no long-term prospects as every muscle group in the body — except for the eye muscles — falls to the genetic condition. Steroid treatments would extend quality of life, but would offer no long-term hope.
"Love him while you have him," Dan Carson remembers hearing.
"It was terrible...I remember being at work, and looking out the window with tears streaming down my face," he remembers.
Since then, the Carsons have renewed hope for their son and his long-term prospects, thanks to cutting edge research and thanks to the generosity of people in Harford County who have supported fund-raising efforts for research that could give rise to an effective treatment being available within the next two years.
Today (Friday) the Carsons, their friends and extended families are holding the sixth annual county bull and oyster roast to raise money for Duchenne's research. In the first five years, about $900,000 has been raised, including an early sum of about $100,000 that has had a direct effect on bringing about the recent positive research developments.
A little bit of background on the Duchenne's muscular dystrophy, its root causes and whom it effects, is in order. First, the pronunciation is essentially do-shun.
Duchenne's affects boys almost exclusively. It constitutes any one of several defects in the genetic code for a protein (dystrophin) that is critical in the maintenance, repair and growth of muscle cells. The gene is found on the X chromosome, of the X-Y chromosome pair that determines sex. The X-Y chromosome combination is the one that gives rise to males, so if a gene on the X chromosome is defective, there is no extra copy on the Y chromosome to compensate. In girls, if the defect is in the gene on one X chromosome, the other X generally carries a good copy of the gene, thus girls are largely unaffected.
Furthermore, Dan Carson explained, the condition isn't necessarily one that can be checked by doing genetic screening of the parents because about half the time the condition isn't inherited, but is the result of a spontaneous mutation. Such was the case for Mark Carson.
Duchenne's is not specific or more pronounced in any ethnic group or any part of the world and shows up in about one in every 3,000 boys born, according to information from the Foundation to Eradicate Duchenne's. The foundation says Duchenne's "is the most lethal and common form of the 20 muscular dystrophies. Every day, two young boys will die from Duchenne's muscular dystrophy."
The relative obscurity of Duchenne's in the general public belies a disorder that affects many lives. The condition causes muscle fibrosis, which is especially noticeable as swelling in the calves.
The Harford push
Upon getting the diagnosis, Dan and Tina Carson were upended. Like many parents who get bad news about the health of their children, they sought others in the same situation and began looking for any options that might be available. As it turned out, the information they had been given when Mark was diagnosed was out of date. While it remained true there was no treatment on the market, there was research and it had been showing promise.
The Carsons would end up making contact with Joel and Dana Wood, of Alexandria, Va., whose son, James, had been diagnosed with Duchenne's in 2000. The Wood family established the Foundation to Eradicate Duchenne, whose focus was, and remains, securing financing to pay for research that will lead to an effective treatment.
When the Carsons approached Joel Wood about helping with fund-raising, most of the foundation's efforts had been focused on securing grants from government and private sources, and it had been meeting with some success. The Carsons, however, took a different approach of organizing community fund-raising events like the annual bull and oyster roast today at the Richlin Ballroom in Edgewood. In the first two years, the Carsons efforts' resulted in the raising of about $250,000.
When the subject of how much money has been raised locally comes up, Dan Carson says he can't say enough about the generosity of the people of Harford County, a generosity that has extended well beyond his family, friends and co-workers. He sometimes refers to those who have helped as angels. It is this generosity that enabled the Carsons, on behalf of the Foundation to Eradicate Duchenne's, to give a grant totaling about $100,000 to Carrie and Stan Micelli, a husband and wife research team working at UCLA. The Micellis, who also have a son with Duchenne's, were pioneering a treatment path that had been unsuccessful against cancer and inflammation conditions, but was beginning to show promise in Duchenne's.
That initial grant of $100,000, Dan Carson recalls, was what helped the Micellis take their research to a level that showed enough promise that a short time later, they received a grant totaling $6 million. Since then, the drug treatment regimen, known as exon skipping, has shown so much promise that the company invested in it saw its stock increase in value from 45 cents a share last year to about $45 a share this year, Dan Carson said.
These days, the Carsons and Micellis are on a first name basis.
An exon is a section of genetic code. In Duchenne's, a particular exon is faulty. The most common faulty exon is the one researchers have numbered exon 51. Mark Carson's faulty exon is numbered 45, and boys with this faulty exon constitute the second largest group of those who have Duchenne's.
In Duchenne's, when cells are synthesizing proteins and they reach the faulty exon, the process stops. The treatment known as exon skipping involves administering drugs that tell the affected cells to resume protein making, skipping the affected code.
Carson notes the belief in the research community is the technique proved unsuccessful in treating forms of cancer and related conditions because the treatment needs to be nearly 100 percent effective to kill off the cancer cells. As it turns out, the treatment is effective in the 15 to 20 percent range. It's not enough to kill all the cancer cells targeted with exon skipping drugs, but when the production of a vital protein goes from nothing to 15 or 20 percent of what is normal, the positive effect is immediate and noticeable.
There have been clinical trials on boys in the largest group, the exon 51 group, in Ohio and the results are regarded as very promising: those receiving the treatment show improvement in a six-minute walking test and systemic reintroduction of the protein dystrophin where none had been present. This is compared to a placebo group that shows no improvement.
An added bonus: the improvement comes with no side effects being noticed to date.
Treatment at hand?
The Carsons are cautiously optimistic about their situation. It is possible a treatment could be available within one to two years. Mark, who'll turn 12 in January, is approaching an age when the effects of Duchenne's become increasingly debilitating.
"We're on the border here. Two years could become five years. That's big," Dan Carson says.
The U.S. Food and Drug Administration's approval process is time consuming. Then there's the matter of the treatment regimen focusing to date on exon 51 when Mark Carson is part of the exon 45 group. There are two schools of thought. One says the drug ends up being approved as a treatment for the exon 51 group only. Another says the treatment approved for exon 51 is also made available to those with other affected gene number sections.
A lot goes into such decisions, Dan Carson explains. That side effects appear to be negligible and the prospects are dim if nothing is done for the boys outside the exon 51 group constitute an argument in favor of opening the drug as a treatment for the larger group of boys with Duchenne's.
Nothing about the treatment, however, is certain, Carson says.
Dan Carson's high degree of understanding of the details of genetic research is impressive, especially considering the subject matter was largely unknown to him prior to 2004. This unusually intense layman's focus on a complicated area of research science is a small example of how the Carsons' lives have changed since Mark's diagnosis.
The fund-raising efforts were another, and were more intense in the early days, Dan Carson says.
"You find that you have to strike a balance," he explains.
Upon first hearing the diagnosis, he, like many parents he has come to know, projected out many years, focusing on the potentially bad times ahead.
Then there was the early focus on fund-raising. In addition to the bull and oyster roast that has become an annual event, there were other efforts, which proved exhausting.
In more recent years, the Carsons have a different perspective on their situation. Having a son with a progressively debilitating condition puts a lot of stress on a family, Dan Carson says, adding, "but it can also bring a family together."
"There are certain things that would be stressful that become secondary to enjoying the moment," he says, noting that the stresses of work, while they remain, are seen from a different perspective.
"You live day by day. You wake up and everyone is good and you go from there," Carson says.
"Our family has been very strong and a very normal family," Carson says. His daughter, Sarah, a student at John Carroll School, is involved with typical teenage activities, to include dating a teenage boy. The subject is of particular interest to the fathers of teenage girls.
Mark, meanwhile, has become quite the history buff. He also enjoys reading — he's been tested at a 12th grade level — watching movies, engineering with Lego and occasional fishing trips with his dad.
There's also a kind of pride in Dan Carson's voice when he talks about his and Tina Carson's son and daughter that is unaffected by any health condition: "She's an absolute sweetheart," he says of their daughter. "They're very close."
For information about making donations, visit duchennemd.org or call the Foundation to Eradicate Duchenne, 703-683-7500.