“Mama Kasey — I spy!” I smile. Robbie wants to play “I spy with my little eye.” She’s actually quite good and relishes the enthusiasm she gets when she’s right. In fact, recently, we were with someone who was unfamiliar with the routine. After Robbie answered correctly, she waited. Though complimented, it wasn’t enough. Robbie gently took this woman’s hand, looked her in the eye and said, “clap.”
Every day with Robbie introduces new revelations of her effervescent personality. She is boisterous and bubbly, bossy but sweet. At 5 years old, she’s exceeded what I expected her to attain even as an adult, given her ultra-rare neurodegenerative diagnosis of SPG47 two and a half years ago.
We are concerned about her mobility. Every growth spurt causes balance issues and muscle tightening. We’ve thought she lost her ability to walk more than once, yet she perseveres and regains her (precarious) equilibrium. We never know if “today” will be the day she’ll never walk independently again.
Robbie and her friend Molly are the driving motivation behind Cure SPG47, the non-profit we parents founded to initiate and fund research towards stopping or slowing the progression of this disease. Molly, too, makes progress daily, especially with speech and cognition. She is forming longer sentences, asking simple questions and commenting on her observations; a true joy for her family to see. She struggles with her walking; there are good days and not so good days. Yet she is most determined; nothing gets in her way of accomplishing what she wants to do.
Like our girls, Cure SPG47’s research is also flourishing. Unwavering determination and initiative from our human neuron research program’s principal investigator, Dr. Darius Ebrahimi-Fakhari , significant support from the Translational Neuroscience Center (TNC), and their partnership with the Manton Center for Rare Disease Research has lead to an international registry and natural history study for AP-4 associated hereditary spastic paraplegia. This study has shown that when any of the AP-4 subunit genes are defective, the clinical phenotype is essentially the same. This connects SPG47 (AP4B1) with three other SPGs: 50 (AP4M1), 51 (AP4E1) & 52 (AP4S1).
Potentially, drug-screening research at Boston Children’s may help identify a treatment, which benefits all four of these diseases. Since the registry and study began last June, 42 cases of SPG47 have been registered, with a total of 110 cases including all four disorders. Most case findings are the result of hundreds of personal emails from Dr. Ebrahimi-Fakhari, our biggest champion. This has connected clinicians and investigators from around the world with the Boston Children’s team. And, due to an overlapping of phenotypes with cerebral palsy, we are expanding the search for AP-4 cases that may be identified through genetic testing of patients with a presumed diagnosis of cerebral palsy.
Dr. Ebrahimi-Fahkari has been invited to present these findings at the American Academy of Neurology conference in May. We have been told that this opportunity could put SPG47 and the related AP-4 disorders on the map very quickly, at a level we could not have anticipated.
In December, the TNC hosted a Cure SPG47 research conference with experts from around the country and overseas. Early on a comment a struck me: “While we’ve learned a lot, there is still much we don’t know.” I fought back tears as the gravity of our intentions and the reality of my scientific ignorance collided. What are we doing? But this feeling was fleeting. I witnessed renowned specialists and brilliant minds carefully and passionately advise, debate and eventually agree on pertinent issues geared towards attaining the utmost safety and efficacy of the therapies that may be identified to treat our children. By the end, I swelled with hope and pride. To choose this path as a parent is terrifying, but to travel it with these experienced and compassionate specialists is exhilarating. And they have mapped our course.
To start, we strive to propagate the news of our research and natural history study to all relevant outlets; we must find the cases we suspect exist. We plan to share reagents (antibodies, mouse models, fibroblast and iPSC lines) to researchers and labs interested in collaboration; there is so much more we can learn. We will begin working with the FDA towards a human clinical trial; our gene therapy research, led by Dr. Mimoun Azzouz at the University of Sheffield, is beginning to show promise. Our action items are ambitious, but so are we.
And myself? I need to hug my daughter, play a game of “I spy,” clap and count my blessings.
Learn more about the Boston Children’s Department of Neurology.