The second annual , held in May at the , concentrated on pediatric precision health care, which , vice chancellor of UCLA Health sciences, acknowledges is key to the future of medicine.
It’s “a major frontier,” said Dr. Mazziotta, also CEO of UCLA Health.
Precision health refers to the use of genomic testing to prevent, diagnose and treat disease with unprecedented specificity. Through analysis of an individual’s genetic code and medical biomarkers, physicians can offer tailored therapies that are often less invasive and longer lasting than traditional treatments.
Precision medicine is used to diagnose rare diseases and is leading to breakthroughs in oncology, cardiology, neurology, genetic and infectious diseases.
“Genetic diseases have led to a revolution in our understanding of biology, with thousands of diseases now decoded since the first positional cloning of disease genes in 1986,” said , the Dr. Allen and Charlotte Ginsburg Endowed Chair in Translational Genomics and director of the , which was recently named a by the National Organization for Rare Disorders. “With these technological advances, hundreds more genetic diseases are being identified, and genomics is now routinely applied to clinical practice.”
The daylong precision medicine symposium, made possible by funding from the Ginsburgs, highlighted the latest developments and challenges in targeted gene therapies for pediatric patients.
Speakers included Katherine High, MD, who detailed her multiyear program to replace a missing gene in the retina to restore vision to children with an inherited retinal dystrophy that is now in clinical use. Noah Federman, MD, director of the Pediatric Bone and Soft Tissue Sarcoma program at UCLA Health, described clinical trial data demonstrating a new drug targeting a specific mutation in infantile fibrosarcoma (a cancer of the connective tissue between bones) that has essentially eliminated the need for chemotherapy and led to complete recovery in many patients. John Tisdale, MD, described a gene therapy to prevent pain crises in sickle cell disease.
While there are only a few FDA-approved gene therapies, there is an anticipated gene therapy approval to treat Duchenne muscular dystrophy, one of the most common lethal genetic diseases, Dr. Nelson says, and a growing number of new therapies soon to emerge for a variety of genetic diseases.
Gene therapy infusions for pediatric patients can compensate for genetic alterations by introducing new genetic material in cells, explains , deputy director of the , while genomic editing allows for changing the existing DNA within a cell.
Ethics, access, equity
The symposium also spent considerable time addressing issues of ethics, access, equity and education around this emerging approach to patient care.
For as revolutionary as gene therapies are, there are many unanswered questions about who can access genomic testing and genetic treatments, said Ellen Wright Clayton, MD, JD, a professor at Nashville’s Vanderbilt University who studies pediatric ethics and genetic testing.
Among the questions Dr. Clayton raised:
- Who decides which infants can undergo genetic testing when there is no clinical indication or obvious condition to prompt it?
- Who pays for such testing?
- What are the objectives when doing whole genome sequencing on neonates?
- How often should children undergo genetic testing and at whose behest?
- What should be done in cases where findings are not actionable?
- What about privacy concerns, especially regarding direct-to-consumer genetic testing?
She noted that genetic testing is most often available at academic medical centers, which means it’s often out of reach for people in rural areas. And clinicians don’t always know what to do with the information uncovered by genetic testing, she said.
Another speaker, Aaron Goldenberg, PhD, a professor at Case Western Reserve University School of Medicine, also discussed the ethical and legal implications of gene therapies for pediatric patients.
Only a tiny fraction of genetic research to date has been done on people of color, so findings are heavily biased in favor of people of white European descent, he said.
“That bias leads to translational biases,” Dr. Goldenberg said. “It leads to ancestry test limitations to genetic testings where tests may not be as meaningful for families from underrepresented communities. The concern is that will also translate to gene-targeted therapies – that gene-targeted therapies developed on research only within certain geographical communities may not be as effective and may be less helpful for families from underrepresented communities.”
Some communities are also reluctant to participate in genetic testing because of past experiences and distrust of genetic researchers and the medical establishment, noted , an associate professor with the who works with the Institute for Society and Genetics and the Institute for Precision Health.
She pointed to the experiences of the Havasupai tribe, whose by researchers at Arizona State University, resulting in a 2004 lawsuit and raising questions about how to ethically include marginalized populations in genetic research. Indigenous people, who are 2.9% of the US population, only represent 0.02% of the genetic research population, she said.
Dr. Garrison noted that the Navajo Nation has had a moratorium on participation in genetic research studies since 2002.
The speakers urged scientists and clinicians — and ultimately policy makers and insurance companies — to consider questions of ethics and access around genetic testing and targeted gene therapies as the science expands.
“The science is the bedrock,” said Dr. Clayton. “But to make this deliver real value to real people, we have so much more work to do.”
