“Losing Connor’s Mind”
by Amitha Kalaichandran
The Atavist, December 29, 2017
I have a pitch below that could be a good fit for The Atavist Magazine. Most of the reporting is complete (including visiting the family during their treatment at Nationwide Hospital, interviews with both doctors), but photos/video could be helpful.
I’m a resident physician in pediatrics and a journalist/writer based in Canada. I write for The New York Times (Well section), Boston Globe ideas (latest is in press), CityLab/The Atlantic (In Press), NYMag, Quartz, etc — links in signature.
Happy to chat via phone too (REDACTED)
FINDING CONNER’S WORDS
A lethal cause of childhood dementia now has a promising treatment.
By Amitha Kalaichandran
With silky strawberry blond hair, and tender cherub cheeks, Conner Beish looks, at first, like any other 5-year old on his birthday last month in Denton, Maryland suburb. Except he couldn’t be more different. Conner has neuronal ceroid lipofuscinosis type 2 – CLN2 for short – an inherited condition that results in a build-up of toxic proteins in the brain which kill off neurons and results in childhood dementia and developmental regression. Children that could once speak, run, and draw, lose these abilities at a rapid rate.
Children like Conner lack an essential enzyme called tripeptidyl peptidase 1 (TPP1) that most of us are born with – this enzyme breaks down the ceroid proteins – a normal waste byproduct – in the brain. Most children with CLN2 die by the time they are teenagers, though others, with different gene mutations (there are 14 subtypes under the umbrella term “Batten Disease”) may live until adulthood.
CLN2 is sometimes dubbed ‘childhood Alzheimer’s,’ and experts like Dr. Alfred Kohlschuetter, a Professor of Pediatrics at the University Medical Centre Eppendorf in Hamburg, Germany, refers to it as childhood dementia. “Some people don’t like me using the term ‘dementia’ in childhood, but it’s the best word,” he explains, in a coarse German accent, “‘De’ means going down, and ‘mentia’ means mental – it’s whats happening with these kids
Like other children with CLN2, Conner developed normally until he was three years old – he ran and played with his older brother (now aged 8, and healthy) and other children. He gave his parents – Hollie and Jeff Beish – kisses and hugs. He loved drawing and coloring. He could listen and understand basic commands like other toddlers. Though his speech was slightly delayed, he was able to speak in two-word sentences. Nothing seemed out of the ordinary. Then, at the age of 3 years and 3 months exactly, Conner had his first seizure.
“At first the doctors thought it was epilepsy…and then we did the MRI and they said it was ‘Doose syndrome’ [a syndrome characterized by severe and frequent seizures],” Hollie Beish tells me, “Then they changed their diagnosis and decided it was most likely to be Batten disease, so they sent his blood off for the enzyme test, and confirmed it when he was four years old – this past January.” By the time the Beish family received the news, a once vigorous Conner was was no longer walking by himself, and was barely managing verbal communication, through sounds, which he stopped making in March.
Late this Spring, the FDA granted expedited approved for a new treatment for CLN2, after a series of promising studies involving mice and Dachshund dogs – the latter who are sometimes born with a TPP1 deficiency – and eventually humans. Kohlschuetter was the lead investigator in the BioMarin-funded multi-center human clinical trial, which had sites in Hamburg, London, Rome, and Columbus Ohio. Late last year, the children’s hospital in Hamburg became the first to treat children with CLN2, with excellent results.
The treatment involves infusing TPP1 directly into the child’s brain through a reservoir tube that is surgically inserted beside the brain’s ventricles. The infusion is conducted in a clinic, over four hours, with the patient sitting or lying down as still as possible.
Conner received the surgery in June, followed 24 hours later with the first TPP1 infusion. He currently receives this treatment every 2 weeks, and since the nearest hospitals – in Maryland or DC – are not yet approved to administer it, he and his family travel via a two-hour flight to Columbus to have the treatment at Nationwide Children’s Hospital, under the direction of paediatric neurologist, Dr. Emily De Los Reyes.
De Los Reyes was largely responsible for advocating for a swift transition to human clinical studies for the TPP1 treatment, and for urging the FDA to approve the treatment so that more children could receive it during a critical period in their development. She recalls that the trial findings were outstanding. “We found that out of the 23 kids who completed the study, all had a remarkable slowing of the disease…in many cases they were able to walk again and maintain their language…all in all we found a 90% reduction in symptoms,” she says. Currently, at the Ohio site, 16 American children and 1 Canadian child are receiving the biweekly treatment. Others receive it in their home states – from New York to Tennessee, to Texas, though only a handful have the resources and skilled staff to administer TPP1.
And it’s not cheap – parents have to fork over $27,000 per infusion ($702,000 a year). The Beish family managed to have it pre-approved through their private insurance, with additional subsidies through the Rare Connections [an organization for families confronted with a rare genetic condition] co-payment network.
“CLN2 is one of the worst forms of Batten Disease,” De Los Reyes tells me, “It’s like the children melt in front of your eyes…first they develop normally and within the span of 6 months they regress…it’s not something we think of in children – it’s almost like Alzheimer’s but on a much more dramatic scale because it really effects every aspect of childhood development, not to mention the parents and the whole family who watch it happen.”
De Los Reyes, who moved to the US from the Philippines in the 1980s and is triple boarded in neurology, child development, and pediatrics, says she was inspired by her own patients to sign up to be the only American site of the large trial. “It’s why I went into this field…the brain is a mysterious thing sometimes, and these conditions are tragic…my script used to be [to these families] ‘I’m sorry, there’s nothing we can do,’ and now I can provide an option.”
Back in Maryland,Hollie tells me that after the first few rounds of treatments, Conner seemed to get worse, but that De Los Reyes warned them to expect that.
“I can say that after the fourth infusion – so in late July – we began to see an improvement,” Hollie tells me, “Around then he began making a hissing sound when he saw a snake in a book. . And just yesterday he gave us a hug – that was incredible.” I can hear the emotion in her voice, and she pauses for a moment. “And, you’re asking me these questions at an interesting time, because last night, during his bedtime story, he pointed to a star and said “star” – his first word in two years…his brother was with us and said ‘good job Conner, you said the word!”
This article will delve into the counterintuitive world of childhood dementia, guided by Conner as the primary narrative vehicle, and how it informs what we understand about child development and memory. Drs. Kohlschuetter and De Los Reyes will be secondary characters. Kohlschuetter can provide an international/European perspective as a researcher studying this condition for over two decades, and his experience with this breakthrough treatment. De Los Reyes represents a staunch patient advocate, while also giving the reader a window into her life as an immigrant to the midwestern United States contrasted and how this is sometimes contrasted with her role as a paediatric neurologist for some of the most complex cases in the country. I also hope to devote a paragraph into how the FDA approves these esoteric treatments, and whether protocols have changed since the Trump Administration gained office. This is also an opportunity to touch upon how the ACA and the ACHA differ in terms of rare disease coverage (i.e. for specialist visits across state lines, etc). Lastly, and space permitting, there was a study published in late July by another German researcher who looked at a different set of medications (ie. not an enzyme, but a drug) for childhood dementia that was promising in mouse models. This research involved looking at brains held at London’s Neurodegenerative Brain Bank, so there may be an opportunity to explore this as one other idea on the horizon, along with other experiments involving gene therapy (i.e. CRISPR-Cas9).