By Shoukhrat Mitalipov and Dr. Paula Amato

Clinicians at Oregon Health & Science University in Portland see some of the toughest cases in the region.

Patients go to OHSU struggling with devastating neurodegenerative diseases, rare forms of cancer and deadly heart conditions. Many of these conditions are rooted in a person’s genes as discrete mutations in our DNA. Even though OHSU health care staff are among the best in the business, it’s no wonder patients worry about passing on these conditions to their children.

That’s why OHSU is exploring a question: What if you could prevent disease at the earliest stage?

Here in Oregon, OHSU is at the very forefront of basic science research to prevent and treat inherited disease. In 2017, an OHSU team generated worldwide news coverage when they reported the successful correction of an inherited mutation in early human embryos that causes hypertrophic cardiomyopathy, a heart disease that can cause sudden cardiac death and heart failure. This disease affects an estimated 1 in 500 people worldwide, including young athletes.

Yet, that deadly disease is but one of thousands of conditions known to be caused by a single gene mutation in DNA. In fact, there are more than 10,000 monogenic heritable diseases affecting more than 600 million people today, with limited options for treatment in some cases.

New technologies, such as the gene-editing tool CRISPR (clustered regulatory interspaced short palindromic repeats) hold enormous promise for correction and preventing the passage of disease from parents to children.

OHSU is a leader in this work, in part due to the foresight of policymakers who developed a regulatory environment several years ago — well before CRISPR became a household word — that enables basic scientific research involving human gametes and early embryos. Today, OHSU conducts its work in a laboratory under intensive ethical and scientific oversight.

In contrast, one example of a widely condemned application of CRISPR occurred late last year with the revelation of the world’s first gene-edited babies born in China.

OHSU is concerned that this development will feed a backlash against the legitimate work of scientists around the world, with some calling for a moratorium on heritable genome editing. Although OHSU concurs that, it’s far too soon for clinical trials, university believes basic scientific research conducted at OHSU is necessary now more than ever. Gene editing and other technologies are advancing rapidly, and it’s in everyone’s interest to ensure the technology is effective and safe.

That’s not to say we don’t face regulatory hurdles in the U.S.

The National Institutes of Health won’t fund these areas of research, so OHSU must rely largely on philanthropy and private funding to do the basic science necessary to test safety and effectiveness of CRISPR and other gene-editing tools in human embryos. And should OHSU’s work advance to the point that it’s ready to treat families, Congress has blocked the Food and Drug Administration from providing oversight for such clinical trials in the United States.

As a consequence, another gene therapy that has been developed at OHSU to prevent the transmission of deadly mitochondrial diseases — called mitochondrial replacement therapy — is now being done overseas. OHSU sees that as a loss for American innovation and leadership in medical research, and it also raises the risk of desperate families finding their way to countries with much less rigorous oversight than the U.S.

OHSU believes patients and families in Oregon deserve the opportunity to benefit from gene therapy technologies developed here. •

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