RESEARCH

November 2022

The Carter Foundation’s research program is centered on advancing cures for Hereditary Spastic Paraplegias and has focused its first endeavors specifically on SPG3A, which, along with SPG4, are the two most common genetic mutations causing HSP.

2021 and 2022

The research programs in 2021 and 2022 have focused on experiments testing several drug therapy hypotheses identified in earlier experiments at National Institute of Health (NIH) under the direction of Dr. Craig Blackstone, and other research centers.

• Human Neurons : The first set of experiments exploring these therapy hypotheses uses human upper motor neurons which have been developed from stem cells (called Induced Pluripotent Stem Cells or iPSC) and have the SPG3A mutation.
• Fruit Fly: The second set of experiments is endeavoring to validate or expand on these findings using the drosophila (fruit fly) living system.
• Mouse: In addition, the Foundation, in collaboration with the Jackson Laboratories and the NIH, has been developing a mouse model which has the SPG3A mutation.

Future

In future experiments, the Foundation hopes to take positive findings and other learnings from the current experiments and advance them using the mouse model. In addition, the mouse model will be used to explore gene therapy approaches to the SPG3A mutation, both in the form of precise gene editing and antisense oligonucleotide (ASO) approaches.

Exploring possible therapeutic approaches in either drug or gene therapy is important to do in a living mammalian model, such as the mouse model we are developing. These experiments are designed to translate the findings of basic science research into living biological systems that are closer to our human biology, and therefore much closer to providing a platform for possible clinical therapy.

Craig Blackstone, MD, PhD serves as the Senior Advisor to the Carter Foundation. He is the Chief of Motor Disorders in the Division of Neurology at the Massachusetts General Hospital and is on the Faculty of the Harvard Medical School.

Darius Ebrahimi-Fakhari from Children’s Hospital is building a registry of all childhood onset Hereditary Spastic Paraplegias(Natural .

Natural history studies are critical for rare diseases. Without them, treatment options will not be available. Future clinical trials related to cures for childhood HSP, including those that might arise from the research program of the Carter Foundation for Neurologic Research, will likely rely on this registry.

study is still seeking participants globally. As of August 2022,the registry had only 11 SPG3A cases.

Dr Craig Blackstone from Massachusetts General Hospital in Boston is one of the leading researchers in HSP, specifically SPG3A.

In collaboration with the Carter Foundation for Neurologic Disease Research, he is testing, both on in vitro and in vivo models, various drug compounds and gene therapy methods with a view to designing clinical trials in children with de novo SPG3A in the near future.

You can watch the presentation of Dr Blackstone research here, starting on minute 24:32: https://videocast.nih.gov/watch=44694