Looking back to late 2011 and the summer of 2012, Jennifer Greene’s memories of her second pregnancy were remarkable for being unremarkable. As far as she knew, everything was proceeding normally, just as it had two years previously with the birth of her son, Gavin.
“You know, I had a healthy pregnancy,” recalled Greene, a former operations manager at the Directors Guild of America. “I went to all my doctor’s appointments, and all the tests came back fine. I had an amnio, and it turned out fine. I took my prenatals, I ate well. Nothing showed up. I thought I was having a perfectly healthy baby.”
Greene speaks these words in the living room of her Porter Ranch home while holding her daughter, Madison Ruby, who turned 3 on July 30. Jennifer’s husband, Brian, sits nearby while 5-year-old Gavin plays with his grandmother, Jennifer’s mother, Esther Bolkin. Madison claps, smiles and flips through the pages of a book.
Diagnosed in September with a rare, crippling and incurable neurodegenerative disease that she shares with fewer than 200 people, Madison has never been healthy.
Still, Brian, who runs the eyelash extension company Glad Lash with his mother-in-law, said he remains optimistic.
“Absolutely,” he said. “I’m not just a glass-is-half-full person, I’m a glass-is-overflowing person. We still hope for the best.”
“I try,” Jennifer said. “But knowing what this is, it’s really hard to stay optimistic.”
Madison has enormous brown eyes and long, curly brown hair. In the photos on the toddler’s Facebook and FirstGiving pages, which the Greenes set up as soon as she was diagnosed with beta-propeller protein-associated neurodegeneration (BPAN), Madison wears a pink tutu and beams a million-watt smile. The smile is even more infectious when you meet Madison in person.
Madison has seizures and frequently wakes up in the middle of the night. She communicates only through crying, leaving her parents to guess whether she needs food, sleep or a diaper change. Madison is not in preschool, and her mother takes her for applied behavior analysis (ABA) therapy 25 hours per week. Despite weekly physical, occupational and speech therapy, Madison neither walks nor speaks. In most respects, she has the cognitive ability of a 1-year-old or younger, her parents said.
“Her life should not be like this. It shouldn’t,” Jennifer said. “She will never be a typical girl.”
Symptoms of the disease will worsen as Madison gets older. She will likely experience considerable pain, Parkinson’s-like symptoms and, potentially, blindness. In all likelihood, the disease will take her life before she turns 30, according to the most recent medical data.
The condition has no cure and, because it is rare, has prompted little research from drug companies. The Greenes are looking to change that.
“She is no different than someone who has breast cancer. This condition is life-threatening,” Jennifer said. “The more money we can raise for her, the more research they can do, and hopefully they will come up with a treatment that will prolong her life. That’s all we’re asking for. This is our daughter.”
Before they could fight on her behalf, the Greenes needed to identify their enemy. For the first three years of Madison’s life, her parents and an army of doctors could not figure out what was wrong.
Madison did not meet any of her developmental milestones, prompting her parents to take her to specialists who declared that the girl had global developmental delay. At 6 months, Madison was hospitalized with a respiratory virus and bronchiolitis. Then the seizures started. Even with extensive therapy, Madison made little developmental progress.
The Greenes continued to look for answers. After more than a dozen visits to geneticists, neurologists, developmental pediatricians and countless tests, the Greenes supplied blood for a whole exome sequencing test — a comprehensive series of genetic tests that, for the Greenes, carried a price tag of $20,000, most of which was covered by insurance. The family was told it would take five months for results, and that the chances of the test revealing anything conclusive were 30 percent.
“But it was our last hope,” Brian said.
Five months later, the family finally had an answer. The BPAN diagnosis placed Madison under the umbrella of 11 categories of neurodegeneration with brain iron accumulation (NBIA) disorders. NBIA sufferers have excessive amounts of iron accumulating at the base of the basal ganglia in the brain. The excessive iron leads to such symptoms as stiffness in the limbs, Parkinson’s, dystonia, vision problems and developmental delays. The NBIA Disorders Association estimates that out of every 1 million people, between one and three have an NBIA disorder.
The BPAN gene, discovered in 2012 by researchers at the Helmholtz Institute in Munich, is caused by a mutation of a gene carried on the X chromosome. The disease is not hereditary, and most of the people diagnosed with it are female. According to Patricia Wood, president of the NBIA Disorders Association, there are now two laboratories in the United States that test exclusively for the BPAN gene.
After receiving Madison’s diagnosis, the Greene family contacted the El Cajon-based NBIA Disorders Association and, through Facebook, connected with other families affected by NBIA throughout the country.
The Greenes quickly launched a fundraiser to raise $35,000 toward a research grant (firstgiving.com/fundraiser/madison-greene). Two weeks into the campaign, Madison’s Mission to find a cure for BPAN had raised almost 20 percent of its goal. Every dollar raised will go the NBIA Disorders Association and will be earmarked for research.
“Every family handles the diagnosis differently,” Wood said. “Some need time to process, and others want to get right in there and do something. Jennifer and Brian want to move right out there and get things done. It’s awesome.”
Once the NBIA Disorders Association has at least $45,000 for the research grant, a proposal will be put out to the research community for bids. The association’s Scientific and Medical Advisory Board will review all proposals and decide who will receive the funding.
At this point, the most current research on BPAN is being conducted at the Oregon Health & Science University in Portland and at the Institute of Human Genetics at the Technical University of Munich.
In terms of possible treatments, the future for BPAN-affected individuals is uncertain. Researchers have created a model to replicate the gene in mice, and Wood said clinical trials are in process for a drug that will slow down the symptoms of a more common form of NBIA, pantothenate kinase-associated neurodegeneration (PKAN). Another PKAN drug designed to potentially cure the disease could begin clinical trials as early as 2016.
The PKAN gene was discovered in 2001, and Wood contends that a 15-year journey from gene discovery to potential life-saving treatment gives research advocates reason to hope.
“Technology is moving much faster today than 15 years ago, so we expect that the BPAN gene will have a shorter trajectory to bring a treatment to our families and could certainly help Madison in her lifetime,” Wood said.
Still, in the fight against rare diseases, every dollar will count. NBIA is rare enough and subcategories such as BPAN are rarer still and therefore do not attract federal or drug company funding.
“It seems unfair that there’s no research for something that’s rare,” said Rachel Rosen, Jennifer Greene’s close friend. “You see group pages for kids with cancer and strangers donating thousands of dollars. With something so rare like this, people seem hesitant to donate. I want people to understand that just because BPAN is rare doesn’t mean it’s not valuable to research.”
Wood agrees. A disease that has affected fewer than 200 people will get far less attention — and funding — than diseases that take millions of lives. Even so, many rare diseases have broken through the anonymity barrier after a famous person has been diagnosed. And the ability to spread the message on the Internet has helped level the playing field in disease advocacy. A rare disease could be one Ice Bucket Challenge away from bringing in serious money and attracting attention.
In the meantime, Wood does not expect the families of the affected to give up the fight. Quite the opposite.
“One reason our families are so motivated to fight and help raise funds is that it affects their children so profoundly, and they know if they do not do it, it might not happen,” Wood said. “The rare-disease community has learned that we have to drive the research.”