Stonington -- In July 2002, Deborah Martin and Bill Knowles drove their cheery identical twin boys to a New London pediatrician from their home in Stonington borough. Martin, now in her early 40s, like most new mothers, kept a close eye on their every move. On maternity leave from her patent attorney's job at Pfizer, she was enjoying the work and bliss of motherhood.
However, at the well-baby check, the doctor confirmed their apprehension -- both boys had a rare genetic disorder called neurofibromatosis. In the twins, the pediatrician diagnosed the disease from the cafe-au-lait spots on their abdomens. Also called von Recklinghausen's Disease or more commonly, NF1, the condition can occur by genetic mutation in half of the cases, and by heredity in the other half.
In 1882, Friedrich von Recklinghausen described the disease that is now more prevalent than cystic fibrosis, muscular dystrophy and Huntington's disease combined, according to the Children's Tumor Foundation. At this time, there is no treatment for the tumors that can form anywhere randomly, and, in 20 percent of cases, can cause learning disabilities, blindness, disfigurement, and even death, according to the National Organization of Rare Diseases.
In 80 percent of cases, the disease is mild. Martin said it took a while for them to absorb the message that "there's this problem, and it's real," she said, and yet they knew so little about it.
They both hold doctorates in the biological sciences, so it came naturally to research NF1. It has been little studied because of its orphan disease status. So-called orphan diseases afflict fewer than 200,000 individuals nationwide. Pharmaceutical companies abandon work to create treatments because the research and development costs are estimated to outweigh the profits.
"When we could cry no more, we began developing plans to find a drug therapy for NF1," reads the journal the couple keeps of the NF Project's inception. While Martin continued to support the family financially, the 54-year-old Knowles segued from working as the vice president and director of research for a privately held pharmaceutical company to his new career -- working from home on the NF Project.
This non-profit program finds and tests already developed drug compounds for their efficacy in treating NF1. Existing compounds on the shelf treat cancer and inflammation, and Knowles said that 30 percent of cancers have the same defective cell signal pathways as NF1. Knowles said that the same drugs "will likely be effective for NF1."
The boys continued to grow, race around the playground, and sing in the car, oblivious to the concern wearing deep into their parents' faces. Family support was difficult, as their extended families live throughout the nation. While the boys attended Pfizer's childcare center, Martin and Knowles used the time to work and to confront good and bad news. Good news came in May 2004: the Board of Directors of New York City-based Children’s Tumor Foundation voted to support Knowles' efforts to advance the NF Project*. That meant greater visibility, connections, and possibly, financial support to test compounds.
A few short months later, however, the bad news came. One of the boys gradually slowed down in his play, didn't want to climb stairs, and began to lose weight.
"I kept asking myself, 'Is there something wrong, or is he just being 2?'" said Martin. After a couple of weeks of worried observation and repeated doctor's visits, Knowles and Martin pushed hard for a team of specialists at Yale New-Haven Hospital to examine their son. Knowles had a fellowship from Yale's pathology department and had retained professional and personal contacts there. That afternoon, the 21-pound toddler had a three-hour MRI. Knowles recalled, with an ashen expression, what the doctor told him after the MRI. "'We found tumors growing on your son's spinal column,'" he said. Visibly shaken and drying fresh tears, Knowles recounted how the team of specialists, including an oncologist, orthopedist and surgeon, operated on his son the next day under a microscope. Periodically, a nurse came out to the waiting room to give Knowles or Martin, whoever wasn't looking after the other son, a progress report. In all, the surgeons' six-hour procedure removed the tumors and reinvigorated the couple's dedication to finding a therapy for NF1.
Martin said she feels "brittle at times," as if they couldn't withstand another blow like the one this past summer. But the couple has met others who are affected with or who care for those with NF1, mostly at conventions and medical symposia out of town. Martin singled out "the will behind those" suffering from NF1, to educate themselves about the disease and survive it, as another strength that bolstered the couple through their harrowing summer emergency. "We had no choice," said Martin, "but to press on doing whatever we could to make sure the best drugs are available for NF1 treatment." Knowles and Martin's dedication to the project has just launched it onto a bigger stage. The National Institutes of Health, Pediatric Oncology Branch, and other clinical centers throughout the country are prepared to begin human trials as soon as the drugs are available, said Knowles.
In the NF Project's Oct. 2004 news release Knowles said, "We are determined to accomplish our mission, but we need a great deal of help and support. The CTF is a small foundation...and has courageously taken on a direct search for a drug therapy." With the help of existing donors and cooperation of drug companies, Knowles and Martin hope someday soon their home will display a plaque that says, "The NF Project, founded here in 2003, discovered a therapy for neurofibromatosis."
*The NF Project is now sponsored by Neurofibromatosis, Inc. and donations designated to support the NF Project can be made to Neurofibromatosis, Inc.
