Robbie Edwards and Molly Duffy were 2-years old, and only a few states apart, when they were diagnosed with SPG47, a genetic disease caused by inheriting a mutated AP4B1 gene from each parent. The only other SPG47 cases then known were nine non-verbal, paraplegic and quadriplegic, severely intellectually impaired children and young adults from four Middle Eastern families. Their life expectancy unclear, as this disease was only first recognized in 2011.

Grief and despair shifted to purpose a few months later when Chris and Kasey serendipitously learned of, and met, the Duffy family. As the tots bonded, their parents plotted. With no research or clinical trial for SPG47 existing, these parents knew that they would need to initiate it themselves. They quickly launched the non-profit Cure SPG47 to fund research towards stopping or slowing the progression of this disease.

Now, Cure SPG47’s research projects are flourishing. With immense generosity from loved ones and strangers alike, they quickly raised enough money to get proof-of-concept research started. But millions of dollars are necessary to fund clinical trials and every donation helps. Early AP4B1 gene therapy research, led by Mimoun Azzouz, PhD, at the University of Sheffield, England, is showing promise. Additionally, the human neuron research program’s principal investigator, Dr. Darius Ebrahimi-Fakhari at Boston Children’s Hospital, has partnered with the Translational Neuroscience Center, and the Manton Center for Rare Disease Research to initiate 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 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 beneficial to all four of these diseases.  Since the registry and study began in June 2018, 44 cases of SPG47 and 111 of all four disorders have been registered. Significantly, many children with AP-4-associated HSP are diagnosed with cerebral palsy before genetic testing is obtained, thus expanding Cure SPG47’s search of patients to those with a presumed diagnosis of cerebral palsy who may be identified by genetic testing.

This Rare Disease Day, Robbie and Molly bask in a one-of-a kind friendship while their parents doggedly pursue treatment, bolstered by the remarkable efforts of their medical and personal community and buoyed by considerable research gains for SPG47. They are unwaveringly committed to sharing their story. There are others out there who could benefit from successful therapies this research may identify. They might never learn of it otherwise. And there are those who, while not impacted by SPG47 or any AP-4-associated HSP, need to know that the particular rare disease that consumes their thoughts and their lives does not necessarily mandate solitude, despair and desperation. It may incite action and collaboration; a decisive path towards treatment. Rare Disease Day is not just about rare disease. It is about life, alliances, and the extent to which people will go to preserve them.