A family’s journey navigating an 8-year-old boy’s rare neurodegenerative CLCN6 mutation highlights diagnostic challenges and hope through emerging gene therapy research.
For families of children with life-threatening neurologic conditions, a diagnosis marks the beginning of an urgent and uncertain medical journey. This is especially true in cases of rare diseases where therapeutic options are limited, clinical trials are scarce, and research is still catching up to the need.
The parents of Paxton Purdy, an 8-year-old boy from Southern California, learned this firsthand when their son was diagnosed with a mutation on the CLCN6 gene in January 2024. This gene “encodes a member of the voltage-dependent chloride channel protein family”; CLCN6 mutations have been linked to severe early-onset neurodegeneration.
While the diagnosis explained his symptoms that were initially attributed to autism spectrum disorder (ASD), it also heightened fears for Paxton’s future and launched a quest for a cure with the help of experts at UMass Chan Medical School in Worcester, Massachusetts. Paxton’s parents founded Cure CLCN6, Inc., a 501(c)(3) organization aimed at raising funds for Paxton’s experimental gene therapy at the University of Massachusetts and to connect with others affected by CLCN6 gene mutations.
In this patient perspective, we spoke with Paxton’s father, Paul Purdy, about the family’s experience, their ongoing collaboration with clinicians and scientists, and the urgent need for progress in treating CLCN6-related disease.
Instead of our days being filled with dread and despair, we have hope and optimism, and this drives us to keep fighting for our son and the other children with CLCN6 mutations that we are finding on this journey.
How would you describe your family’s experience with the health care system — from Paxton’s first symptoms to diagnosis and now, as you await treatment?
Purdy: Paxton was suspected of [having autism] when he turned 1 and began early intervention services, specifically applied behavior analysis (ABA) therapy, speech therapy, and occupational therapy. All of his challenges at that time were attributed to autism — global developmental delay, apraxia of speech, poor motor planning, hypotonia, and intellectual disability.
When Paxton was 5, he began having seizures. He had undergone microarray testing when he was 2, looking for markers to explain autism or intellectual disability. He then underwent more genetic testing looking for markers to explain epilepsy, and nothing came up. The CLCN6 mutation was not discovered until an epileptologist ordered testing for him since the epilepsy was refractory. The health care we received was appropriate based on the autism diagnosis, and the medical providers and therapists we interacted with were great.
Purdy: It wasn’t until we received the CLCN6 mutation diagnosis that things became discouraging. The genetic counselor can only go on the information available and what current treatments are available. However, I do find it frustrating as a parent to know that the technology and ability to create gene therapies for genetic mutations is possible, but we were given zero direction on what to do or who to contact [to pursue these options]. We were left in shock and in the cycle of grief to navigate this new rare disease world.
The other families that have reached out to us at Cure CLCN6, Inc. have reported similar stories. They were told their child has this mutation, but it has only recently been diagnosed, so not much is known about it except that it is neurodegenerative and 2 of the 4 children reported in the literature have passed away. The families we’ve been in contact with are in the United States, Mexico, and Scotland.
Can you share how the collaboration with UMass Chan Medical School was initiated and what it has meant for your family’s care journey?
Purdy: [Upon receiving his diagnosis] I relentlessly looked for doctors, researchers, hospitals, and universities that may be able to work with us. There were some phone calls with researchers, but the research hospitals and universities we reached out to did not respond to our inquiries. One night I came across a news article about a family in Oregon who had a son with an ultra-rare mutation, and they were working with UMass Chan Medical School to develop a gene therapy. I thought, ‘That’s what I want for Paxton!’ I reached out to the UMass Chan Medical School Horae Gene Therapy Center, and they responded right away to set up a call with us.
It has been a rollercoaster of emotions, as all I wanted when we received the diagnosis was for someone to say they can help us. But as I am learning on this journey, genetics is incredibly complex, and it takes years to develop a gene therapy. Also, there are things that can go wrong in the development process, and the procedure itself has risks. There is also the fact that there are limitations to what gene therapies can do right now — not to mention the overwhelming price tag of $1.5 million that this project has.
Overall, we are incredibly grateful and fortunate to be in this position and to have this opportunity. Instead of our days being filled with dread and despair, we have hope and optimism, and this drives us to keep fighting for our son and the other children with CLCN6 mutations that we are finding on this journey.
In what ways could this research and investigational treatment help inform future approaches to developing therapies for other rare diseases?
Purdy: Gene therapy as a field is still in its infancy, so researchers are still learning with each project and study that is being done. One of the biggest challenges with treating mutations affecting the central nervous system (CNS) is crossing the blood brain barrier. With this project, they may use some newer capsids that can bind more effectively to the transferrin, which means that many more of the cells can be treated. If this delivery method is found to be safe and efficient and is ultimately used, it would provide real-time evidence on its effectiveness, and this would have major ramifications on more effectively delivering therapeutics to cells in the brain.
What should health care providers understand about the needs and challenges faced by families navigating a rare disease diagnosis and treatment?
Purdy: I remember when we received the diagnosis and were told that this mutation is neurodegenerative and that there is no treatment and no cure. [Clinicians] told me that they would learn more about this mutation by studying Paxton, but my only thought was, ‘What can I do to help my son?’ I would have felt some relief and had more direction if the genetics team had told me that while there is currently no treatment and no cure, the technology and ability to develop a treatment — and 1 day, even a cure — exists, and that there are research hospitals and scientists who may be willing to work with us if we can fund the project.
I understand that this is considered experimental and there are likely liability concerns with suggesting this to patients, but I would have felt a lot better knowing that something could be done, despite the price tag, and having some leads or recommendations on who to contact would have alleviated a lot of grief and anxiety.
How can clinicians best support and advocate for patients and families throughout the diagnostic and treatment journey for rare diseases?
Purdy: The journey from initial symptoms to diagnosis can take months, if not years for most patients with rare diseases. After learning more about rare diseases, especially ones that impact the CNS, there is a consensus that if a child is exhibiting 2 or more challenges in neuromuscular areas, then whole exome testing should be done. This could be a combination of autism (especially when nonverbal), intellectual disability, poor motor planning, hypotonia or hypertonia, feeding difficulties, seizures, digestive issues, or sleep disturbance.
Many children will have these traits without a genetic mutation, but we are learning that many of these mutations present very similarly with these neurologic challenges. So, if clinicians are seeing patients with 2 or more of these symptoms, they should refer them to a geneticist and order whole exome sequencing.
In many cases, like with Paxton’s, a mutation can be neurodegenerative, so time is critical. When that diagnosis is made, I understand that doctors are only going to use US Food and Drug Administration (FDA)-approved treatments, but many parents, like me and my wife Kristin, are willing to pursue these opportunities and fundraise to develop novel treatments. When it comes to ultra-rare diseases, if the families of the affected children don’t take the lead, then the research and development is not going to happen.
I would want clinicians to at least let these families know that these opportunities are out there and to form relationships with research hospitals that may be willing and able to work with these families on novel treatments. I would also want them to refer families to patient advocacy groups for the respective disease, so collectively we can show a need for funding the research and development into treatments for our respective diseases and mutations.
What additional reflections from your experience might be valuable for clinicians to hear?
Purdy: Having a child with special needs is incredibly challenging on all levels, especially in terms of the emotional and mental toll it takes on parents. When a child has a rare disease diagnosis that can lead to death, we are not only grieving the childhood and life we envisioned for them before they were born, but we are now struggling with the reality that our child may pass away before us. This is a devastating experience for us, and it is not a transitory one. Please be patient with us, we are doing the best we can despite the circumstances.
Tori Rodriguez, MA, LPC, AHC
https://www.neurologyadvisor.com/features/rare-neurodegenerative-disease-diagnosis-child/
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