Rare Community Profiles is a Patient Worthy article series of long-form interviews featuring various stakeholders in the rare disease community, such as patients, their families, advocates, scientists, and more.
In Pursuit of Progress: From SPG47 Diagnosis to Rare Disease Research
If your child was the 10th person in the world diagnosed with a rare genetic condition, what would you do?
In 2016, Kasey Edwards came face-to-face with this question when her daughter Robbie was diagnosed with the SPG47 subtype of hereditary spastic paraplegia (HSP).
This elusive disorder has intertwined itself with Kasey’s life, impacting her daughter and fueling a personal determination within her.
Although she was uncertain and frightened after the diagnosis, unsure what the future would bring, Kasey hoped she would change the world to give Robbie the life that she deserved.
Driven by a commitment to alleviate her daughter’s challenges and help others receiving this diagnosis in the future, Kasey and her husband Chris, along with another set of parents whose daughter was also diagnosed with SPG47, co-founded Cure SPG47 (now Cure AP-4), a 501(c)(3) nonprofit organization that aims to advance research and find a potential cure for AP-4 HSP, which includes the subtypes SPG47, SPG50, SPG51, and SPG52.
Their journey, fraught with both obstacles and victories, garnered attention far beyond their immediate community, shedding light onto the realities faced by rare disease families.
As Kasey navigates this complex landscape of research and hope, her story serves as an inspiration, guiding the path towards a future where rare diseases are met with determination and resolve. In her discussion with Patient Worthy, Kasey discusses what HSP subtype SPG47 is, research updates, and how her daughter is doing today.
Kasey and Robbie’s Story
Kasey’s pregnancy had been relatively uneventful. At and following birth, Robbie seemed healthy. But as Robbie grew older, small nagging concerns began to grow. By July 2015, Robbie was not meeting the same milestones that her brother and peers had reached. Says Kasey:
“We were aware that she was globally developmentally delayed. She had difficulty reaching milestones in speech, high motor and gross motor skills, and cognition. This led us to visiting the specialist development program at Mass General. After a thorough assessment, he suggested that we pursue an MRI.”
The family scheduled the MRI for August and set out to enjoy the remainder of the summer. What they never expected was that they would not be waiting until August for more care. During a family vacation at Cape Cod, Robbie had a prolonged absence seizure and had to be medevacked to Boston Children’s Hospital.
At the time, she received the MRI which found a thin corpus callosum and decreased myelination of white matter. Then, at 18 months old, doctors also noticed that her head was smaller than normal and suggested that, by the size of it, something may have happened during fetal development at around 21 weeks old.
Kasey explains that, at this time, the neurologist suggested that her daughter might have a genetic condition. She was ready for Robbie to undergo genetic testing. Whatever came next, the family felt like they were ready to handle.
Of course, receiving a diagnosis for a rare genetic disease is extremely challenging and overwhelming. The family found themselves reeling—and it became even tougher when Kasey realized that there was almost no published literature on hereditary spastic paraplegia subtype SPG47.
United for Advocacy
As she dove into the three existing research studies, Kasey began uncovering some basic information about hereditary spastic paraplegia. She shares:
“I learned that HSP has over 80 different subtypes based on the affected gene. I also discovered that the other nine people who were known to have this diagnosis were not easily available to communicate with, being in difficult-to-access, third world countries.”
Searching for community, Kasey began joining every HSP-associated Facebook group she could find. Even if others in the group didn’t have HSP subtype SPG47, she assumed that HSP shared a common symptom of lower-limb spasticity. At the very least, she could learn more about how others managed this symptom.
She was surprised, however, to meet the Duffy family—a family just a few states away whose daughter was around the same age as Robbie and who also had SPG47. Kasey was filled with excitement; she couldn’t reach out fast enough. Kevin, the Duffy patriarch, responded right away. Kasey says:
“It was absolutely surreal. I also think that was the beginning of the nonprofit. The seeds were planted as soon as we met the Duffy family.”
After meeting the Duffy family, and prior to launching the foundation, Kasey mentioned to her friend—who worked in marketing at Boston Children’s Hospital—that she had met another family affected by SPG47. Her friend offered to introduce her to the PR team, and Kasey agreed. Suddenly, people wanted to speak to the families about what SPG47 was. Kasey knew that beginning a foundation was the ideal next step.
Cure SPG47 was born in 2016.
People Magazine
Kasey’s story, as well as the Duffy family’s story, was featured in People Magazine in December 2016. This led to the nonprofit earning a few thousand dollars in donations. The community also rallied around the Edwards family, with her neighbors donating $2,500.
This financial benefit and press coverage allowed Kasey to catalyze change through the foundation. She shares:
“We began pulling together the board and had this amazing network, including the Director of the Translational Research Center at Boston Children’s Hospital. We were able to align ourselves with researchers who were interested in looking into SPG47 and the AP4 subunit. We connected with those researchers and everything just kind of fell into place. Dr. Ebrahimi-Fakhari also proposed drug screening research, which we provided seed funding for.”
What is Hereditary Spastic Paraplegia (SPG47)?
As the Foundation grew, so did their knowledge about what SPG47 is. Kasey explains:
“SPG47 works like a tire on a car. The three other genes, SPG50, SPG51, and SPG52, are like the other tires. AP-4 consists of those four genes. Each of these AP-4 subtypes is associated with a defective autosomal recessive gene.”
The National Foundation for Rare Disorders further describes AP-4-associated hereditary spastic paraplegia as:
“A group of neurodevelopmental and slowly progressive neurological disorders that generally present with global developmental delay, moderate-to-severe intellectual disability, impaired/absent speech, small head size, seizures and progressive motor symptoms. Low muscle tone (hypotonia) in infancy develops into high muscle tone (hypertonia), resulting in spasticity of the legs that leads to the inability to walk and wheelchair reliance.”
There are an estimated ~200 people worldwide diagnosed with AP-4-associated HSP. Kasey notes that AP-4-associated HSP often masquerades itself as cerebral palsy. She notes:
“Many children diagnosed with cerebral palsy may not be examined or looked at further. I believe that, with more parent-driven research, we might see a more significant amount of children who were diagnosed with cerebral palsy but actually have hereditary spastic paraplegia.”
Cure AP-4 Today
Although the nonprofit began as Cure SPG47, it has since expanded to become Cure AP-4. As the Cure AP-4 website shares:
“The mission has since expanded to include all four AP-4 related disorders due to shared natural history, goals and patient/family needs. We refuse to accept the bleak prognosis which our children face. We have decided to fight. The purpose of this organization is to study and seek a cure for all AP-4 HSP disorders. We aim to improve the quality of life for children impacted by AP-4 HSP by accelerating the research for cures and treatments and providing support for patient therapies critical to their well-being and rehabilitation.”
One of the organization’s main focuses is driving research into the full spectrum of AP-4 hereditary spastic paraplegia. With a slight laugh, Kasey says:
“At one of our first neurology appointments, we asked the neurologist if there is any way to know how much protein she was producing, if at all. We were told no, unless we studied it in a lab. That sounded so unattainable to me at the time. Fast forward seven years and we have done all of this research.”
Some of the research supported by Cure AP-4 includes:
A natural history study at Boston Children’s. This study, spearheaded by Dr. Ebrahimi-Fakhari, includes over 90 SPG47 patients.
A proof-of-concept gene therapy study for the AP1B4 gene. Kasey explains that this gene therapy has shown restoration of losses in mice models. By mid-2024, she believes that human clinical trials will begin. While she feels hopeful for potential gene therapy solutions, she also shares:
“Gene therapy, and I’ve said this often, still terrifies me a bit. These kids are not terminal. They are happy and joyful. So to put them on a therapy that really hasn’t been studied for the past decade is scary. If I ever started something where my daughter, or any child, ended up worse off, I would be devastated. Having these other therapies in the pipeline offers me some comfort.”
Initial drug screening. So far, Cure AP-4 has provided initial funding to screen FDA-approved therapeutics. This led to a grant from a biotech provided to Dr. Ebrahimi-Fakhari to evaluate a chemical compound that has been identified to restore deficient proteins in the AP-4 complex to almost wild-type level, with next steps being to see how it could be optimized for patients.
Work with Unravel Bio. Cure AP-4 has joined a collaborative effort with Unravel Bio, a biotech organization who is using RNA sequencing and machine learning to identify FDA-approved drugs for off-label use. Says Kasey:
“They have already come back with a few that they’ve predicted might help therapeutically and we’re waiting for more data to see if any are still in the running. The problem at this point, with too many potential therapeutics, is that we are part of an ultra-rare community. We can only do clinical trials with so many people, so we really have to be choosy about what we’re trialing on our kids.”
Maintaining a Positive Perspective
Outside of her work with Cure AP-4, Kasey does her best to ensure that Robbie lives a happy and fulfilled life. She shares:
“My daughter is 10 years old now. She is mostly in a wheelchair although we do have a walker to keep mobility in her legs in case there are therapies on the horizon that can help. But she’s so much more independent in the wheelchair. She is a blessing. She is sweet, sassy, funny, and doesn’t mind getting in trouble if she makes someone laugh. People at school call her ‘the mayor’ because students gravitate towards her. She’s the class clown. I feel so lucky that she doesn’t seem to recognize that she has any developmental or mobility differences. She genuinely just enjoys life—and I am so grateful to be on this journey with her.”
Of course, there have still been obstacles along the way. When asked how she has remained resilient throughout, Kasey credited her positive perspective. She explains:
“Raising a child with special needs comes with deep challenges. It requires navigating your own path forward and forging your own trail. Your entire life requires figuring out how to live a new normal. To thrive, you have to just accept it. This isn’t going to be the life you pictured. You’re going to run into problems. You have to let go of expectations every day. Remember that nobody expects anything of you other than getting through the day. I just remember what has come from this diagnosis. That it has taken one of the most devastating things a parent could face to see the best of humanity: people who will step up and go out of their way to help make our life easier. I look for glimmers every day. It’s hard in the beginning. But if your child is having a good day, if they find something hilarious, treasure that moment. Celebrate the little things that make your day a little brighter, a little better. Taking the pain away from the initial diagnosis was cathartic for me, and I hope others see that they are not alone here.”
If you would like to keep up on Kasey and her journey, and receive some tips on staying positive, check out her website Cartwheels in Chaos.
