ResearchHere is a map view depicting the location of patients enrolled in our research on Adapter-Protein 4 (AP-4)-related Hereditary Spastic Paraplegia at this time:
The Manton Center for Orphan Disease Research at Boston Children's Hospital is dedicated to developing methods for understanding, diagnosing and treating rare disorders. We are interested in enrolling patients with AP4-associated Hereditary Spastic Paraplegia in order to create a patient registry and learn more about the cause, progression, and underlying genetic basis of these conditions.
Diagnoses of interest include patients with mutations in the following genes:
Participant enrollment entails:
- Informed consent conversation with Manton Center study staff (in person or via phone)
- Written consent and medical record release paperwork
- Clinical history questionnaire
- Possible blood sample collection
There is no cost to participate, and travel to Boston is not required. All enrollment can be completed remotely. If you believe you or your child may be eligible for this study and you are interested in learning more:
Please contact:Premsai Nagabhyrava, MPH
Translational Neuroscience Center | Boston Children's Hospital
For Medical Professionals:The Translational Neuroscience Center at Boston Children's Hospital has established a Human Neuron Core to help researchers better understand neurological disorders and hopefully lead to earlier diagnosis and better treatment for neurological disorders. The purpose of this study is to create cell lines from bio-samples from patients with specific neurological disorders to look for the cause of the disorder, and to develop new diagnostic tests and treatments for the disorder. We hope that with the knowledge gained from research done through this Core, we might be able to help the participants in this study in the future.
We are currently collecting samples from patients with AP4-related HSPs (SPG47, SPG50, SPG51, and SPG52). Since the clinical presentation and the molecular mechanism for all AP4-related disorders is likely the same, there is potential that induced pluripotent stem cell research into SPG47 will inform us about SPG50, SPG51, and SPG52.
If you would like to learn more about participating in this study, please contact our Research Study Coordinator at 617-919-1476 or NeuroCore@childrens.harvard.edu
Current AP-4 HSP Research Projects:The International Registry and Natural History Study for Adapter-Protein 4 (AP-4)-related Hereditary Spastic Paraplegia has shown that when any of the AP-4 subunit genes are defective, the clinical phenotype is essentially the same. This connects a total of four SPGs: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) & SPG52 (AP4S1). Dr. Darius Ebrahimi-Fakhari of Boston Children's Hospital is pursuing a drug screening experiment on fibroblasts derived from AP-4 related HSP 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 AP-4 related HSPs. Potentially, the drug screening research may help identify a treatment which benefits all of four of these diseases. A detailed clinical characterization of SPG47 is available through the American Journal of Medical Genetics.
Cure AP-4 has engaged Dr. Mimoun Azzouz of the University of Sheffield to develop a gene therapy proof-of-concept for SPG47. His team has developed an AAV9 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. Early proof-of-concept research looks promising thus far.