At age 4, Nathan Milto was a typical preschooler: he enjoyed singing songs, playing on the computer and practicing hockey slap shots with his Dad in the basement of their Indianapolis home.
But in a just a few months, a rare neurodegenerative disorder known as Late Infantile Batten disease would transform Nathan's happy childhood into a living nightmare.
By his fifth birthday, the disorder had caused Nathan to lose his eyesight, and at age 6 he was put on a feeding tube.
"We had absolutely no idea this would happen," said Tricia Milto, Nathan's mother. "He was a perfect baby – Nathan actually hit all his milestones three to six months ahead of where he should be – until he turned four."
As Nathan approached his seventh birthday in 2001, he had lost his ability to walk and talk and was bedridden, unable to communicate except by way of facial expressions and an occasional hand gesture.
Meanwhile, Tricia and her husband Phil Milto had been noticing similar problems with Nathan's younger brother, P.J., who at just three and a half years old was also having trouble seeing and communicating.
Like his brother, P.J. became one of only approximately 500 children worldwide diagnosed with Batten disease. P.J.'s condition progressed so quickly that just two years later the six-year-old was uncommunicative and confined to his bed.
According to Dr. David Pearce, an associate professor at the Center for Neural Development and Disease at the University of Rochester Medical Center who has been researching Batten disease for more then 10 years, the cruelest part of the inherited disorder is the delay of noticeable symptoms.
"You'll have a child who is a fully formed five-year-old and then you will gradually take all of their functions away – starting with their vision and then their brain eventually deteriorates," said Pearce.
"The body tries its best to compensate for the [defective gene] but it reaches a threshold [around age five] where it just can't cope anymore," said Pearce. "That results in a system breakdown."
But standing idly by to watch his two sons slowly die was not an option for Phil Milto, who has now spent more than 10 years trying to find a treatment for children with Batten disease.
For Parents Looking for a Cure, Roadblocks Abound
Milto established Nathan's Battle Foundation, a non-profit biotech firm that raised millions to fund gene therapy trials at the Medical College of Cornell University, which has since developed a drug that has proven to slow the progression of the disorder.
A lack of funding for additional clinical trials for the drug – which in its first form succeeded in slowing the progression of the disorder – has halted its development.
Like Milto, Lance Johnson, the executive director of the Batten Disease Support and Research Association, said losing his daughter to the disease spurred him into action.
"When you get diagnoses like Batten disease all your hopes and dreams are shattered – they disappear into vapor," said Johnson, whose daughter Lorena died at age 22 in 1993.
Johnson said that Lorena began having vision problems at age six and developed seizures at age nine.
She went blind at age 13, was unable to walk at 15, lost her speech at 17 and by her 19th birthday was incontinent and hooked up to a feeding tube. At age 20, Lorena had lost her movement in her hands and fingers. She died two years later.
"She went from being a perfect little girl to the total other side of the spectrum," said Johnson. "The hopelessness that you feel as a parent when you see your child declining – I don't know how to describe it."
"The grief cycle just runs over and over again every time there is another loss of a function – the ability to walk or talk – the cycle starts over again," he said.
Johnson, who had once dreamed of becoming the president of the Ohio railroad he worked at, said that his daughter's diagnoses changed his path. Instead, he joined the Batten Disease Support and Research Association and helped it become the leading distributor of information about the disease as well as a fundraiser for research into treatments.
In addition to the gene therapy trials, a stem-cell therapy trial is also underway, said Johnson. The treatment is pending FDA approval before it can proceed.
"Just like gene therapy is looking for funding, we're looking for the FDA to approve us before anything else can be done," he said.
"I am optimistic," said Johnson. "We don't know which therapy will be the one that will work; it's possible that it could be a combination of therapies."
Despite Parents' Dedication, Batten Disease Struggles for Attention
Rochester Medical Center's Pearce said that despite parents' dedication to development of treatments, because so few children are affected by the disease recruiting scientists to research it is not easy.
"The families work incredibly hard [to bring attention to the disorder], but there are still only a few of us in the world working on the research," said Pearce.
"Unfortunately science is like any business – the more dollars we throw at it the more likely we'll be able to fix it," adds Pearce.
Competing with more well-known diseases such as AIDS and cancer for funding and attention is difficult.
But Pearce argues that researchers and doctors wary to get involved are overlooking the fact that breakthroughs for Batten disease will likely be used to understand other neurological disorders.
"Anything we discover for Batten disease will be applicable for many other diseases too," said Pearce.
"We don't understand how the brain works in its normal sense so while studying it in terms of Batten disease we may find something that might be applicable to Parkinson's or Alzheimer's – I'm sure of it."
While their parents continue to try to find funding for the gene therapy treatment, Nathan and P.J. sit together in their shared room and listen to DVDs.
The boys require around-the-clock care, said their mother, who has recently begun to worry that Nathan may not have much longer to live.
"Every day is getting harder," said Tricia Milto. "I do feel like with Nathan I'm playing tug of war right now. I feel like someone tugging him one way saying its almost time and I'm saying I'm not ready."
The Miltos have accepted that Nathan and P.J.'s conditions are too advanced to respond to any of the pending treatments, but say that the way the disease has affected their sons has changed the way they look at life.
They hope their hard work will one day result in a cure for the hundreds of other children suffering from Batten disease.
"I want no one to imagine what we're going through," said Phil Milto. "It was my dream to raise our kids and coach them in sports."