What is SPG47?
Hereditary Spastic Paraplegia, type 47, otherwise known as "SPG47", is an ultra-rare neurodegenerative disease. Children afflicted with this genetic disorder generally present with symptoms including global developmental delay, microcephaly, seizures, malformation of the brain, and hypotonia (low-muscle tone). The few patients that learn to walk independently tend to lose that ability a few months or a few years later as they develop hypertonia (high-muscle tone) and muscle spasticity. Of the ~20 confirmed cases of SPG47 in the world at this time, the first 9 patients have progressed to loss of mobility in some or all extremities, and are severely intellectually challenged. Because of the extreme rarity of SPG47, very little research has been conducted to date, and there is no known treatment or cure at this time.
SPG47 is caused by a mutation in the AP4B1 gene. It is an autosomal recessive disease, which means that both parents have contributed a defective recessive gene to the child. The result is that the child is unable to correctly produce a protein which is required for proper functioning of the AP-4 adaptor complex in the central motor neurons in the brain.
The Cure SPG47 non-profit organization was founded in 2016 by families of two of the known patients. 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 SPG47. We aim to improve the quality of life for children impacted by SPG47 by accelerating the research for a cure or treatment and providing financial support for patient therapies critical to their well-being and rehabilitation.
Current SPG47 Research Projects:
» Dr. Darius Ebrahimi-Fakhari of Boston Children's Hospital is pursuing a drug screening experiment on fibroblasts derived from SPG47 patients. The process begins with obtaining skin cells from the patient and the same gender parent. IPSC stem cells are developed from the tissue, and then differentiated into central motor neuron cells which can be maintained and studied in a lab. The goal of the project is to test whether various compounds which are FDA-approved for other disorders might offer some benefit to the cells affected by SPG47.
» Cure SPG47 has engaged Dr. Mimoun Azzouz of the University of Sheffield to develop a gene therapy proof-of-concept. His team will develop a viral vector capable of delivering a good, working copy of the AP4B1 gene to the central motor neurons of a knockout mouse as well as fibroblasts derived from SPG47 patients. If successful, this research will provide the basis for pursuing human clinical trials in the coming years.
» Dr. Ebrahimi-Fakhari has also initiated the first International Registry and Natural History Study of AP4-related Hereditary Spastic Paraplegias, the NHx-AP4 STUDY. This includes patients with SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4S1) and SPG52 (AP4E1). A detailed clinical characterization of SPG47 is available through the American Journal of Medical Genetics. If you would like to participate, please contact the Boston Children's Hospital Research Study Coordinator at 617-919-1476 or firstname.lastname@example.org.