WASHINGTON — As the Batten Disease Support and Research Association celebrates its 30th anniversary, the group’s executive director says scientists are edging ever closer to treatments for the incurable genetic disorder.
Margie Frazier said the organization she’s headed for five years is the only one that represents all 14 forms of Batten disease, also known as neuronal ceroid lipofuscinosis, or NCL. Headquartered in Columbus, Ohio, BDSRA helps families mainly in the United States and Canada, but last year assisted people in 34 countries.
“Batten is a life-limiting autosomal recessive disease that shows up at different times in children,” Frazier said. “But all of our kids will have significant seizures, vision loss, cognitive decline and early death unless they get access to treatment.”
Frazier spoke to Batten Disease News at last month’s Rare Diseases & Orphan Products Breakthrough Summit, an annual event in Washington sponsored by the National Organization for Rare Disorders (NORD). Frazier’s association is one of 260 patient advocacy groups belonging to NORD — and the only Batten-related group that was at the Oct. 16-17 summit.
Brineura’s FDA approval a milestone
Earlier this year, the U.S. Food and Drug Administration approved the first-ever therapy for Batten disease — a milestone that both NORD and Frazier are praising.
Brineura (cerliponase alfa), developed by BioMarin Pharmaceuticals, is an enzyme replacement therapy for a form of Batten known as CLN2. It is directly administered into brain fluid, treating the underlying cause of CLN2 disease by helping replace the TPP1 enzyme that youngsters with the condition are missing.
“We have children all over the world getting ERT [enzyme replacement therapy],” Frazier said. “Since its approval, we’ve seen many more children we didn’t know about come forward with CLN2.”
The FDA approved Brineura for children 3 years and older with this form of the disease — one of the most common of the 14 types of Batten, which is itself rare. Batten occurs in only two to four of every 100,000 births in the United States, according to a National Institutes of Health website.
Brineura is one of the world’s most expensive medications. At $27,000 per biweekly infusion, it takes $702,000 a year to treat one of the 150 or so babies born each year with the CLN2 form of Batten — including 20 or so in the United States.
And Brineura is not a cure. It just delays major symptoms, so that children treated with it can keep walking and talking until around 6 years of age.
“Many more clinical trials are in the pipeline for gene therapies,” Frazier said. “There is so much new information every single year in therapy development, and in the regulatory environment.” Keeping up with what’s going on is an important way for the association to support the parents of children with Batten disease, she said.
Batten diagnosis ‘takes way too long’
Frazier, who has a doctorate in social work from the University of Chicago, is a mental health professional with experience at a number of state and nonprofit hospitals in Ohio and Illinois. She also headed an AIDS patient advocacy group at the height of the 1990s crisis with that disease.
“We’ve been working steadily with families to get their children into treatment with Brineura. For the most part, our experience with Medicaid and insurance systems has been positive,” said Frazier, adding that the situation in Great Britain is more challenging.
“We’re deeply concerned about our parents in the U.K. because the NHS [National Health Service] is refusing to pay for Brineura,” she said. “I’m in touch with my cohorts in the U.K. right now. They have five new diagnoses of CLN2 and cannot access treatment.”
An estimated 14,000 people worldwide have Batten disease, said Frazier, whose association — founded in 1987 — has three full-time staffers in addition to herself. Another five part-time vendors work with the organization on projects ranging from website development to medical conferences.
Every year, the association holds a family conference. This year’s event in Pittsburgh attracted 430 participants. The next one, themed “Walk the Line to a Cure,” will be July 19-22, 2018, in Nashville.
“Batten is a devastating diagnosis that often takes way too long,” Frazier said. “We’re working diligently on getting earlier diagnoses for kids. For example, with some of the earlier-onset forms of the disease like CLN2 and CLN1, a child will have a first unprovoked seizure and may be treated for epilepsy for years before any genetic testing is done, when in actuality they have Batten disease. So it’s imperative that we get treatment as soon as possible.”
Natural history studies are crucial
Because of its prevalence in Finland, Sweden and the Canadian province of Newfoundland, Batten was until recently seen as a Northern European or Scandinavian disease. That view is now outdated because “with genetic advancements, we’ve learned about so many more different forms of Batten,” Frazier said. “There’s no real ethnic or regional pattern, and it strikes boys and girls equally.”
In CLN2, seizures are often the first symptoms, and in CLN3, it’s generally blindness. Those are the two most common forms of Batten in the United States, though in South America the CLN6, CLN7 and CLN8 versions appear to be more common, Frazier said.
The relatively high prevalence of Batten in Argentina has led to the opening of a specialized Batten clinic in the city of Córdoba. The disease is also prevalent in Australia, Canada and South Africa.
“We believe that as genetic testing awareness among those treating kids with neuronal ceroid lipofucsinosis broadens, we’ll begin to see more cases,” Frazier said. “You can do a 23andMe [genetic test] to find out if you’re a carrier. But the truth is, many pregnancies are unintended and people are not testing. We wouldn’t really expect you to test if you didn’t know there was any Batten in your family. That’s not something you’d go after. But if Batten is in your family, we assist with carrier testing.”
Frazier said the natural history information her group has collected on CLN2 over the years shows how quickly children with the disease can deteriorate. A disease’s natural history shows how it progresses over time.
“These kids have a precipitous, rapid and horrifying dropoff between ages 3 and 5,” Frazier said. “I just talked to a mom who was getting her daughter enrolled in enzyme replacement therapy. She told me, ‘My daughter could lift a cup last week, and this week she can’t.’”
The association has 900 people in its closed Facebook group. Membership costs $40 a year, and the association has several hundred members. But as Frazier said, “We help anybody who calls us. They don’t have to be a member.”
Batten disease makes headlines
Frazier said the disease received widespread publicity this summer when Lester and Celeste Chappell of Springville, Utah, lost three children — Christopher, 20; Elizabeth, 19; and James, 15 — in three consecutive days to Batten. Their youngest son, Samuel, also has the CLN3 form of the disease.
“They’re a wonderful family,” Frazier said. “This is obviously a terrible thing for families to go through. We have many families who have lost three kids to this disease, though the Chapelles might be the only ones who will lose four.”
Frazier also had warm words for the VanHoutan family of suburban Chicago, whom she called the heartbeat of Brineura because of their efforts to spearhead FDA approval of the drug.
Tracy and Jen VanHoutan lost their 11-year-old son, Noah, to Batten in March 2016 — seven years after he was diagnosed with CLN2, and a year before Brineura came on the market. His sister Laine, now 11, also has Batten and has lost her ability to walk, talk, eat and see.
“The VanHoutan family has lost one child to CLN2 and will lose another one because she is too far progressed in this disease to get the enzyme,” Frazier said. “But they continue to push for funds for research, along with our association.”
In fact, when Frazier started at the association five years ago, it was just beginning to talk with the pharmaceutical industry. Now the association works with seven or eight companies.
“Also, when we first started, some of the genetic companies might have had only three or four of the 14 forms of Batten on their panels,” she said. “It’s almost unheard of now for me to walk up to one of the testing companies, look at their sheet and for them not to have all 14.”
The BDSRA has a partnership with Invitae to screen Batten carriers who want to become parents. The Invitae Epilepsy Panel analyzes 189 genes associated with causes of epilepsy, including neurodegenerative conditions like Batten. Results are usually available within 14 days.
The screening gives someone who has watched a sibling die of Batten disease the “peace of mind that they can go ahead and have a baby, and know they did everything they could to protect their child,” Frazier said. “That’s worth a $475 genetic test.”