OHSU

Mitalipov Gene Therapy Research Frequently Asked Questions

This list of Frequently Asked Questions provides information about the OHSU gene therapy method developed through research in nonhuman primates led by Shoukhrat Mitalipov, Ph.D. Media inquiries may be directed to OHSU's office of Strategic Communications, at 503 494-8231.

What was the goal of this research?

The purpose of this research was to continue development of a gene therapy method that prevents serious diseases from being passed from mother to child. This gene therapy approach was designed to address mutated genes carried in cell mitochondria. Mitochondria are a structure that exists in all cells (thousands per cell). Mitochondrial DNA contains 37 genes. When a mother's egg cell contains a large number of mitochondria with mutations, serious diseases can occur in her children. Simply put, the procedure OHSU has developed "swaps out" mutated DNA so that these inherited diseases are prevented.

How does it work?

The Mitalipov lab's procedure requires an unfertilized egg cell from the mother and an unfertilized egg from a healthy donor. The nucleus from each cell is removed. The nucleus from the mother's egg cell is then placed in the cell body (the cytoplasm) of the donor egg cell. By doing this, 99 percent of the mother's genetics are preserved in the new egg cell. However the mitochondria containing mutated DNA is replaced with the donor's healthy mitochondrial DNA. This illustration helps explain the process. The egg cell is then fertilized through existing assisted reproduction technologies and then re-implanted in the mother so that it can develop into a healthy baby.

What did this research prove?

Previous research conducted in the Mitalipov lab in 2009 using monkey egg cells proved that this procedure was possible and that healthy baby monkeys were the result. This research illustrates that the procedure is also possible in human cells and the resulting egg cells were normal and healthy upon observation.

If this procedure is developed into a human treatment, who would benefit?

If approved, this procedure would help families with known genetic disorders that have been previously passed from mother to child. In the past, these families had two choices: To have children with a high-likelihood of disease or families could use the adoption process. This procedure would offer families a new option where the risk of mitochondria disease is removed while maintaining more than 99 percent of the parents’ genetic information.

What would need to occur before this is adopted for human use?

Several steps need to occur before this procedure is used in the clinic. Additional safety and efficacy testing in patients must be conducted during clinical trials . Based on these trials, the procedure would need to be approved by the Food and Drug Administration. We also believe a public discussion about the procedure is a healthy part of this process.

What form of ethics review took place before the research began?

This research was funded through private dollars due to existing restrictions on the use of human eggs and embryos for federally funded research. However, a significant amount of ethics discussion took place before work with human eggs began.

At OHSU, the researchers consulted with ethicists and other experts within OHSU's Institutional Review Board (IRB) and the OHSU Stem Cell Research Oversight Committee (OSCRO.) The OSCRO reviews research involving human embryonic stem cells at OHSU to ensure that all federal and state regulations governing the conduct of stem cell research are met and that all human embryonic stem cell research is conducted in accordance with the general principles expressed in the National Academies’ Guidelines for Human Embryonic Stem Cell Research. The IRB reviews biomedical and behavioral research that involves humans in order to protect the rights and welfare of the research subjects.

OHSU researchers also reviewed the results of the Nuffield Council on Bioethics, an independent body in the United Kingdom that examines and reports on ethical issues in biology and medicine. The council recently conducted a 6-month review of the topic because this gene therapy approach is being thoroughly considered for approval in that country.

The executive summary of that report states the following:

“Due to the health and social benefits to individuals and families of living free from mitochondrial disorders, and where potential parents express a preference to have genetically-related children, on balance we believe that if these novel techniques are adequately proven to be acceptably safe and effective as treatments, it would be ethical for families to use them, if they wish to do so and have been offered an appropriate level of information and support.”

The entire report can be found online.