Rare diseases were the focus of Research Day 2021 at CHOC, with several panelists stressing the necessity of collaborating across specialties and partnering with the community to find breakthrough treatments and to reduce health disparities.
The all-day webinar on Nov. 17 featured several CHOC doctors and scientists who discussed the importance of rare disease research; emerging technologies, diagnostics, and therapeutics for rare diseases; and how to enhance the diversity of rare disease clinical trial populations.
“I really hate to tell my families, ‘I’m sorry, there’s nothing we can do,’” said Dr. Raymond Wang, a metabolic disorders specialist and director of the Foundation of Caring Lysosomal Storage Disorder Program.
“The guiding principle I have is to give hope to our patients and families,” said Dr. Wang, who spoke on the panel, “CHOC Studies that Highlight the Importance of Rare Disease Research.”
Dr. Sharonne Herbert, PhD, a clinical child and adolescent psychologist and CHOC’s inaugural Diversity, Equity, and Inclusion officer, led a discussion on “Enhancing the Diversity of Rare Disease Clinical Trial Populations.”
She echoed the thoughts of others by noting the importance of forging partnerships with the communities CHOC serves to reduce health disparities.
“It truly is difficult to reach health equity clinically if our research is inequitable,” Dr. Herbert noted. “If we strive for health equity in such research areas as enrollment and recruitment, research design, dissemination of information and data collection, it will make a significant impact in expanding our awareness as well as our understanding of various medical presentations.
“Now’s the time to minimize or eliminate the inequities that persist and move toward health equity.”
The right thing to do
There are some 7,000 rare diseases worldwide. About 70 percent of these disorders are genetic, and about half of these diseases affect children.
Sadly, noted Dr. Wang, less than 10 percent of rare diseases have some form of treatment.
Dr. Wang led an effort that has turned CHOC into the largest infusion center in the U.S. for the treatment of Batten disease, a fatal disorder. CHOC’s leading-edge therapy for Batten disease has shown to be effective in slowing the progression of the disease, which leads to waste products building up in the brain.
“Rare disease research is a calling,” Dr. Wang said. “You must be willing to go above and beyond the standard of care to seek such kinds of therapies. You must persevere past a lot of obstacles. It’s easy to say, ‘Sorry I can’t do anything.’ But I can’t fathom just stopping. The right thing to do is often not the easiest thing to do.”
Current clinical research on rare diseases at CHOC highlighted by Dr. Wang includes studies involving gene therapy for Sanfilippo A syndrome, GMI gangliosidosis and mucopolysaccharidis type 1, and an early access program for Niemann Pick C disease treated by the experimental drug arimoclomal.
Translational research efforts cited by Dr. Wang include stable genome editing of multiple Salla syndrome mutations as well as multiple mutations caused by Pompe disease.
Research critical to advancements
Dr. Michael Muhonen, co-medical director of the CHOC Neuroscience Institute, discussed his potentially game-changing work in the treatment of spinal muscular atrophy and hydrocephalus.
CHOC currently is part of a multi-center clinical trial that is seeking Food and Drug Administration-approval for a lumbar shunt catheter he helped to design that would allow for the direct injection of the drug into cerebral spinal fluid.
Dr. Muhonen came up with a way to directly access the back of patients’ necks – as opposed to their lower spines — using a variety of already FDA-approved catheters. This more direct access should lead to better outcomes, Dr. Muhonen explained.
“If you look at the mission of CHOC – to nurture, protect, and advance the health and well-being of children — if you’re going to do that, you’re not going to do it by just running a clinical hospital,” Dr. Muhonen said. “You’re not going to make advancements unless you have research. And CHOC has really stepped up to the plate recently to make research part of our mission.”
To treat hydrocephalus, the buildup of fluid in the ventricles deep within the brain, Dr. Muhonen is devising a one-way valve system that will drain fluid from the brain. His goal is to do away with the traditional method of draining the fluid into the abdominal cavity via a shunt with a 4-foot-long tube. Shunts must be replaced 10 times in a person’s lifetime because they fail for many reasons. For example, they can become calcified and break apart or get twisted into a knot.
Dr. Ashley Plant also participated on the panel. She is an oncologist who left CHOC a year ago but still collaborates with CHOC researchers in her new position at Lurie Children’s Hospital of Chicago.
Dr. Plant is working on a vaccine to treat kids with the devastating diagnosis of Diffuse Intrinsic Pontine Glioma (DIPG), a tumor that starts in the brain stem and kills kids by the time they are between 9 months to 1 year old.
One initial goal of Dr. Plant’s ongoing clinical trial is to get median life expectancy for DIPG patients extended to 15 months.
“It definitely takes a village to get something like this off the ground,” Dr. Plant said of her study.
Funding remains a roadblock in rare diseases research, since drug companies are resistant to invest a lot into potential therapies for such a relatively small number of patients, the panelists noted.
But that’s not discouraging doctors and scientists from pursuing new therapies.
“Some of what I’ve done I attribute to luck, if that’s the right word,” Dr. Muhonen said. “I like to try things out of the box.”
Panelist and noted rare disease specialist Dr. Wayne Grody, a professor in the departments of pathology and laboratory medicine, pediatrics, and human genetics at the UCLA School of Medicine, urged doctors, especially those early in their career, to consider rare disease research.
“Watch out for opportunities that may come out of left field,” Dr. Grody said. “It might not be any topic you thought you might be interested in, but it may lead to something.”
Improving quality of life
Dr. Jose Abdenur, chief of the division of metabolic disorders and director of the metabolic laboratory at CHOC — one of only a few such labs in the United States – noted during the panel discussion on “Emerging Technologies, Diagnostics and Therapeutics for Rare Diseases” that there are existing technologies and therapies to treat kids with rare diseases.
He said patients with metabolic disorders who also are hypoglycemic benefit from technology used to treat diabetics.
“Even if it doesn’t translate into a cure,” Dr. Abdenur noted, “we can help improve the quality of life of a lot of patients.”
Experimental diets also have helped some children with rare diseases, he said.
“When you work in rare diseases,” Dr. Abdenur added, “the only way to really have an impact is to take a holistic and comprehensive approach (to treating patients).”
Dr. Virginia Kimonis, tenured professor in the Division of Genetic and Genomic Medicine in the Department of Pediatrics, with appointments in neurology, pathology and medicine at the UCI School of Medicine, is one of several UCI faculty members who provide genetics services at CHOC.
She detailed some of the work she’s involved in and stressed the importance of teamwork.
“I can’t do any of this work without a village of researchers, collaborators, and funding agencies,” Dr. Kimonis said. “Funding agencies are very important for rare disease researchers. Hopefully, we will make a difference in the lives of these patients.”
Earning patients’ trust
Speaking on the final panel topic, “Enhancing the Diversity of Rare Disease Clinical Trial Populations,” Dr. Candace Taylor Lucas, co-director of LEAD-ABC (Leadership Education to Advance Diversity – African, Black and Caribbean) at UCI Health/CHOC, said rare disease researchers must view patients as participants at the start of each study.
“They are key stakeholders in the work we’re doing,” Dr. Taylor Lucas said. “Their perspectives and experiences carry great value and can inform what we’re doing along the way and afterward as well. It’s vital for us to pause and listen to children with rare diseases who are already minoritized by their disease and whose experiences are unique.
“We must work to earn their trust. We must earn the ability and demonstrate on a consistent basis that trust is something we value.”
Dr. Keith Norris, a national health policy leader and a professor of medicine, UCLA Division of General Internal Medicine and Health Services Research, called race a social construct that has no direct relationship to biology. Dr. Norris recently was elected to the National Academy of Medicine for making substantive intellectual, scientific, and policy contributions to the areas of chronic kidney disease and health disparities in under-resourced minority communities.
“The differences in disease outcomes between groups are primarily due to how society treats and groups people, and the number of resources and opportunities that are given to groups of people,” Dr. Norris said. “The differences in disease outcomes between groups are primarily due to how society treats, groups, and the number of resources and opportunities that are given to groups of people.”
This reality, he said, needs to be in the mindset of all healthcare professionals.
“When we see our patients,” Dr. Norris said, “we want to be thinking about not ‘What’s wrong with them?’ but “What did we do to them?’ If we take that view, that will allow us to approach our patients and communities with a different level of compassion and empathy.”
Dr. Norris added at another point in the discussion: “So-called ‘hard-to-reach’ populations aren’t hard to reach. They’re hardly reached.”
Pursuing partnerships
A key to reducing health equities, panel members agreed, is developing relationships and partnerships with communities and their leaders before clinical studies are designed.
“We need to look at ourselves as not just researchers but also advocates,” CHOC oncologist Dr. Sonia Morales said. “We need to advocate for our patients. I think we can start changing the mindset of ‘us vs. them’ and be more inclusive.”
Dr. Morales said community-partnered research is key.
“You’re engaging the community you serve,” Dr. Morales said. “This should be foresight, not hindsight. From the start, set up a community advisory board of patients. That way, you’ll bring in the real experts who are living with the disease. We can design interventions, but they need to be informed by the community.”
On the cusp
Dr. Terence Sanger, CHOC’s chief scientific officer, noted on the panel on emerging technologies that CHOC and partners such as Rady Children’s Hospital in San Diego are at a critical juncture when it comes to research into rare diseases.
“I think we really are on cusp of a very exciting time for children, and we in Southern California are fully intending to lead this charge,” Dr. Sanger said.
Fellow panelist Dr. David Dimmock, senior medical director of Rady Children’s Institute for Genomic Medicine, agreed.
“It’s my firm belief that Southern California is going to lead this if we choose to and decide to get ahead of this,” Dr. Dimmock said. “If not, we’re going to be playing catch up.”
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