AAV9 gene therapy is a technique that allows doctors to treat a disease by inserting a healthy gene into a patient’s cells. Since Tallulah is missing a healthy copy of the gene that causes SPG56 (the CYP2U1 gene), it is possible to use a modified virus to deliver a good copy of the gene to her motor neurons.
The functioning copy of the gene is inserted into the cells of her body by a carrier called a vector and this is genetically engineered to deliver the gene. The vectors are most often modified viruses. These viruses are carefully designed so they don’t cause disease in the person like a common virus could. Instead, the modified virus delivers and “infects” the person’s cells with a good gene- in this case, a healthy CYP2U1 gene.
Once inserted into nucleus of Tallulah’s cells, the good copy of the defective CYP2U1 gene would enable her body to generate the naturally missing protein that is causing the disease.
This state-of-the-art gene therapy could halt and/or reverse the disease in children affected by SPG56.
Currently, Our Moon’s Mission is undertaking the Proof of Concept study. This is the first of 3 extensive and complicated phases of a developing a gene therapy for humans: Proof of Concept, clinical studies and finally clinical trials (giving the gene therapy to humans).
We predict the Proof of Concept study will take 1.5 years.
Proof of concept study
The Proof of Concept study will use a vector and a disease model to provide convincing evidence that establishes (to the satisfaction of regulatory bodies like the FDA or TGA) that there is a therapeutic lead. This would consist of showing that AAV gene therapy can have a meaningful impact on survival or behavioural / motor performance in a disease model of SPG56. If successful, this research will provide the basis for pursuing human clinical trials in the coming years.
Our genetic consultant Dr Neil Hackett has designed an adeno-associated vector (AAV) which is being manufactured by biologists, virologists and engineers at Vector Builder in the USA.
Researchers at the Jackson Laboratory in the USA will then develop a bespoke disease model which will have a CYP2U1 gene dysfunction that closely resembles this same dysfunction in patients with SPG56.
Through this study we will gain valuable insights into progression of SPG56. From these studies the team will develop a natural history study on the models which will help researchers better understand the causes of the more complex behavioral phenotype associated with this disease.
Researchers will extensively test the vector on the model in the laboratory to ensure it is safe and effective. This will be done by testing at various stages of development and at a variety of dosages. A full toxicology study will ensure the therapy is completely safe.
With this data the research team will ascertain the optimal methodology for the administration of the gene therapy to maximise therapeutic effect.
Finally, the study will be published and made available for peer review and presented to the necessary drug administration authorities for approval to commence clinical trials.
