Scientists call for reconsideration of mitochondrial replacement moratorium

Researchers have put forward a case to reconsider mitochondrial replacement moratorium in the U.S. so as to alleviate mitochondrial DNA mutations that are passed onto children from their mothers and end up suffering from incurable and fatal illnesses.

Researchers say that a much-studied form of mitochondrial replacement (MR) could prevent the transmission of such diseases from mothers to children and hence researchers argue that the U.S. moratorium that includes MR should be reconsidered through a process that engages the public, medical professionals, the U.S. Food and Drug Administration and Congress.

According to the researchers such a process could clarify the benefits of the procedure — namely, the births of healthy children — and decouple it from misplaced concerns about genetic editing of embryos. MR therapy simply replaces mutation-bearing mitochondria in oocytes (unfertilized, un-implanted eggs) with donated mutation-free mitochondria.

The moratorium

In 2016, legislation was passed that prohibits U.S.-based research in which a human embryo is intentionally created or modified, the study notes. While MR does not modify or “enhance” the nuclear genome, according to Eli Adashi, a professor of medical science at Brown University’s Warren Alpert Medical School, replacing mutation-bearing mitochondria with donated mutation-free mitochondria falls under the general category of procedures prohibited by the moratorium.

In their commentary, Adashi and Cohen point out that the authors of the legislation are anonymous and that no congressional hearings, floor discussions or public engagement took place before its passage.

The authors surmise that the legislation may have been intended primarily to prevent embryo loss, a concern that does not apply to MR. A public process of reevaluating MR’s inclusion in the moratorium could help to clarify that MR takes place before an embryo exists. The donated mitochondria are placed within unfertilized eggs, which can then be fertilized so that women can give birth to genetically related, disease-free children.

Impact of the moratorium

The moratorium deprives affected American families of the opportunity to prevent inherited, incurable and agonizing mitochondrial disease in their children, the authors contend.

Mitochondrial diseases include Leigh syndrome, a progressive and fatal disorder characterized by lesions on the brain that may lead to heart, kidney, vision and breathing complications, and Alpers Disease, a neurologic illness that causes seizures, dementia, spasticity, blindness, liver dysfunction and cerebral degeneration.

The moratorium may also induce American families to seek care outside of the country, according to Adashi and Cohen. They noted that a U.S.-led team in Mexico may have prevented Leigh syndrome in a child by replacing the mutation-bearing mitochondria of oocytes with donated mutation-free oocytes.

“This development calls into question the regulatory utility of a national moratorium in a globalized world wherein cross-border care is increasingly prevalent,” Adashi and Cohen wrote in the study. It also creates risks, the authors assert, because there is no FDA oversight of these procedures that take place outside the U.S. border.

A path forward

Adashi and Cohen recommend that a coalition of patient and advocacy groups, medical professionals and legislators convene congressional hearings on the prevention of mitochondrial diseases. They also suggest convening a public meeting of the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee, charged with regulating reproductive technologies, to review the state-of-the-art procedure.

They also recommend stringent FDA oversight, the conditional approval of biologic licensing applications, clinic-specific licensing, possible sunset contingency provisions, and long-term intergenerational follow-up of the children of mothers who undergo mitochondrial replacement to determine the continuing safety and efficacy of the intervention.

In the U.K., a careful 15-year vetting process resulted in a vote in Parliament that approved MR under stringent regulatory oversight. In the U.S., on the other hand, “Congress legislated a statute that prohibits the FDA from adjudicating research into a range of procedures hereby treating the issue with a broad brush,” Adashi said.

“They spent 15 years studying it — the science, the safety, the ethics — and they asked the British public what they thought,” he added. “Now MR is legal but regulated by an agency that has been proceeding very cautiously, with just one clinic licensed to perform the procedure.”

What this means, Adashi said, is that parents who are at risk for transmitting mitochondrial disease to their children may now undergo MR and have children who are not born with agonizing and untreatable diseases. American parents, Adashi and Cohen wrote in the commentary, deserve nothing less.