Gene-targeted therapies have the potential to revolutionize medicine through treatments that modify or replace disease-causing genes with healthy variants. Gene therapy commonly involves using a modified virus to deliver the healthy genes into a patient’s cells. Once there, the new genetic material instructs the cell to produce the missing or defective protein that is causing the disease. Other approaches include gene editing, like with CRISPR-Cas9.
To discuss the importance of these new therapies and work to address any inequities which may exist in accessing them, experts met at a recent Rare Disease Day event at the U.S. National Institutes of Health.
People all across the rare disease space, and in health and medicine more broadly, are working to address these issues.
“Many key organizations across the rare disease community are encouraging dialogue, organizing educational conferences, creating new staff positions and funding equity and health disparity grants,” said Deanna Portero, Management Analyst at the NIH’s National Center for Advancing Translational Sciences (NCATS). “There is increased agreement that something must be done to make sure that gene-targeted therapies aren't just for the wealthy and well connected.”
Some organizations are developing individualized experimental therapeutics for patients regardless of ability to pay, she said. The federal government has issued executive orders to advance racial equity. And the National Academies of Sciences, Engineering and Medicine recently put out a report on advancing anti-racism and DEI in STEM organizations.
There are currently more than 20 FDA-approved cellular and gene therapy products available for a range of diseases. The number of gene-targeted therapies in clinical trials is growing rapidly, with more than 2,000 active and upcoming trials registered on ClinicalTrials.gov.
Diversity and DNA Sequencing
It’s not just gene-targeted therapies that are struggling with equity. All of genomics is currently grappling with a major diversity problem. For instance, in 2009, 96% of all human gene samples studied came from people with European ancestry. By 2016, researchers in places like India and China had started including more Asians and Latinos in their research. But in the United States, the number remained stagnant. Meanwhile diversity in the actual U.S. population is growing, with a majority minority population under the age of 16.
Tshaka Cunningham is a co-founder and chief scientific officer at Polaris Genomics, and is an advocate for increasing diversity and representation in genomics.
“Genomics and rare disease research is going to need to keep pace with this growing diversity,” Cunningham said at the NIH event.
Less than 2% of all DNA ever sequenced has been from people of African descent, he said.
Fortunately, genetic sequencing is becoming more and more accessible.
“That should be very exciting to all because that means we're going to have more sequencing data, which is going to allow us to understand more about individuals and the diseases that they suffer from, and how to tailor treatments for them,” Cunningham said. One goal, he said, is to transition from one-size-fits-all medicine into a new practice of precision medicine. This means tailoring treatments to individuals by considering their genome, lifestyle, health history, family history as well as looking at how people respond to different treatments.
“We're not only going to get an idea of who is susceptible for what rare disease, but who's going to respond best to what treatment,” he said.
The Next Generation of Scientists
Including more diverse populations in research and clinical trials is just one step toward a more inclusive future that allows new therapies to benefit everyone. Progress is needed, Portero pointed out, in diagnosis, support systems, opportunities to participate in research and rigor of therapeutic testing. That could increase trust among minority populations, which has long been low due to a historic — and present — disregard for their welfare.
“The discussion of trust (should) begin with how we will change the state of affairs so that we earn trust, instead of discussion of how to obtain it before it is due,” she said.
One of the best ways to earn patient trust and increase equity across the entire system is to increase diversity at every level.
"A new generation of diverse scientists will help us address racism at the highest levels of academia, industry and government to create a truly level playing field,” Cunningham said. “We're counting on the future generations to help us solve this problem.”