A message of hope echoed through UCSF’s William J. Rutter Center in February, as speakers at a Rare Disease Symposium discussed scientific breakthroughs and successful medical treatments that had been mere dreams a few years ago.

Nadav Ahituv, PhD, director of the UCSF Institute for Human Genetics, gave a particularly rosy outlook on where things are heading.

“There's been amazing progress in sequencing,” he said. “There's been amazing progress in delivering genes for gene therapy, and finally, there’s been amazing progress in gene editing. And all of those really allow us to move forward in terms of rare disease research.”

Ahituv spoke at a symposium presented by the UCSF Catalyst program, “Where Science Meets Silence: Innovation in Rare Diseases.”

The symposium—a partnership between UCSF Innovation Ventures, the UCSF Institute for Human Genetics and Fondation Ipsen—convened advocates, scientists, doctors, venture capitalists and leaders in the biotech industry to discuss strategies for finding cures and treatments for the more than 7,000 rare diseases that afflict more 350 million people around the world.

Catalyst hosts the symposium every two years. While the Rare Disease Symposium in 2024 focused on diseases that impaired people’s vision and on rare epilepsies, this year’s event dedicated several presentations to hearing loss.

Genes for hearing loss have been mapped and cloned, Ahituv said, which has led to the first gene therapy for hearing loss. “Stem cell therapy for hearing loss is about to begin the first in-human trial,” he said. “I think this is really exciting.”

The symposium featured encouraging talks from Rick Guidotti, a fashion photographer who founded and directs Positive Exposure, a nonprofit dedicated to showcasing the beauty and humanity of people with rare diseases, and from Rebecca Alexander, an author and motivational speaker who lives with Usher syndrome, which causes hearing and vision loss.

Jacque Duncan, MD, chair of UCSF’s Department of Ophthalmology, said Alexander—one of her patients—is “my friend and hero.” Duncan showed photos of Alexander participating in extreme athletic events, climbing Machu Picchu, skydiving, and swimming from Alcatraz to raise money for UCSF. Alexander has two master’s degrees from Columbia University, is a practicing psychotherapist, and a disability rights advocate.

“There is really nothing that will stop Rebecca from anything she wants to accomplish,” Duncan said.

Alexander praised Duncan for her bedside manner, saying other clinicians should learn from her example. “You have the ability to have a major impact on a person's life, because you are the gatekeeper of whether they believe that they will be able to have a main goal in their own life, or whether they will feel that sense of gloom and doom,” Alexander said, speaking on a large screen from New York, where she now lives. “That's a tremendous responsibility, which I don't think that many clinicians actually realize that they have.”

 

Tribute to Atul Butte

The symposium typically puts a spotlight on the challenges in developing, funding, and getting approval for treatments—while also showcasing the inspirational stories of what many of the speakers are doing to overcome those challenges.

For all the science, the symposium makes sure the patients are never forgotten.

“The fundamental premise of why we're all here today is that every person living with a rare disease deserves a right to diagnosis, care, dignity, and compassion,” said James Levine, MD, PhD, president of Fondation Ipsen and holder of more than 100 patents.

The symposium paid tribute to the late Atul Butte, MD, PhD, a pioneering computational scientist who founded and directed UCSF’s Bakar Computational Health Sciences Institute and also served as chief data scientist for UC Health. Butte died last year of a rare spinal cord cancer at age 55. 

Butte’s wife, Tarangini (Gini) Deshpande, PhD, a cancer biologist, entrepreneur, and partner in Green Sands Equity, said the loss of her husband has shaped her view of the rare disease landscape.

“It is great to see all of the innovation that is happening across the ecosystem on things like diagnostics,” Deshpande said in conversation with Aenor Sawyer, MD, the executive director of Innovation and Entrepreneurship at UCSF Innovation Ventures. “But at the end of the day, all of that innovation is of little value if it doesn't actually reach the patient. That's what I want to focus on.”

Deshpande said that during Butte’s battle with cancer, he came up with a term: “scalable privilege.” Because of Butte’s eminent status in the field, he could reach the top doctors and easily navigate health care systems.

“We realized that privilege was rare,” Deshpande said. “How do we get that to others? How do we scale that privilege?”

“What do patients who don't have access to this level of expertise do? How do we make this a more equitable situation for other patients with regard to access?”

Butte could call an eminent doctor in Boston, but Deshpande said “there just simply aren’t enough hours in the day” for those doctors to see all the patients who they want to see, or who want to see them. But perhaps, Deshpande mused, patients could be compared to other patients with similar genetic profiles, and then the knowledge from Boston could be shared with, say, an oncologist in California’s Central Valley.

Deshpande is working on a book of “Atul-isms,” a collection of coinages like “scalable privilege” that will help people understand the issues at stake. “One of my favorites is, ‘Data is not the fruit, data is the soil,’” Deshpande said. “Hiding within large amounts of data is the knowledge that can change the world and change the life of a single patient.”

 

Moving Mountains: Reyna’s Story

In a panel moderated by Roopa Ramamoorthi, PhD, director of UCSF’s Catalyst Program and InVent Fund, Jainu Jogani told the story of his daughter, Reyna, who has CDKL5 Deficiency Disorder, a devastating epileptic encephalopathy caused by loss-of-function mutations in the CDKL5 gene. Jogani is the co-founder of Child’s Cure Genetics Research, a parent-founded organization dedicated to developing precision gene therapies for rare genetic disorders in children.

Reyna was born in 2017. At only 20 days old, she started making random movements that became more severe over time, ultimately manifesting as seizures. Jogani described the path to a diagnosis and a challenging year, with Reyna having as many as 60 seizures a day.   

“What are the treatment options for this disorder?” Jogani asked. “Unfortunately, there were none, which started our journey to fuel research for CDKL5.”

Jacinthe Gingras, PhD, the scientific advisor to Child’s Cure Genetic Research, said that while they can never lower the bar on scientific rigor, they must be creative and acknowledge the urgency that parents feel in seeking to develop treatments for their children’s diseases.

Nalin Gupta, MD, PhD, chief of the division of Pediatric Neurosurgery at UCSF, said he was close to a clinical trial to treat CDKL5, thanks in large part to Jogani’s “energy and effort.”

“There are many steps and that’s why there are many teams,” Gingras said. “The sooner we all talk, the better, so that all the pieces are in place.”

Gupta said the landscape has changed so much over his career. “We’re really in a new era,” he said. “Being able to treat a disease process is totally different from 25 years ago when I started.”

Still, he said, there’s no substitute for a clinical trial. “The only way to know if something works is to do this in humans, in patients,” he said.

The key, Jainu said, is to keep hope alive. “You’re not alone on this journey,” he said. When he started out, he emailed every biotech and pharmaceutical company he could find online. “Just make sure that your story is heard,” he said. Eventually, he made connections that led him to Gingras, Gupta and others, who have been able to make meaningful progress.

 

New Technologies and Diagnosis for Hearing Loss

In the day’s closing panel discussion, Payal A. Anand, AuD, CCC-A, director of the multi-site

Audiology Program at UCSF, said that a test revealing hearing loss is often only the start of someone’s journey. “The hearing loss does not explain the underlying condition,” she said. “Two different tests can have two different causes. This is where diagnostics is important.”

Hearing loss is a very common problem, affecting 1.5 billion people around the world, said Konstantina Stankovic, MD, PhD, FACS, chair of the Department of Otolaryngology – Head and Neck Surgery at Stanford University School of Medicine. 

“The causes of hearing loss are very versatile,” Stankovic said, noting more than 400 syndromes and 200 genes that cause hearing loss.

She said therapies have been a long time coming because of the challenge of working deep in someone’s ear. The cochlea—a spiral-shaped structure in the inner ear that plays a crucial role in hearing—is tiny and surrounded by bone. Stankovic said it’s “the size of Lincoln’s upper face on a penny, from his forehead to his mouth.”

Yet new tools from micro-endoscopes to tomography are making it possible to unlock some of the mysteries of hearing, with “tremendous therapeutic implications,” she said.

Dylan Chan, MD, PhD, director of Pediatric Otolaryngology at UCSF and director of the Children’s Communications Center, said 6,000 to 10,000 babies a year are diagnosed with congenital hearing loss.

“Childhood hearing loss is incredibly important because it leads to permanent delays and has societal costs,” Chan said. “And because of that, there is an enormous system of care within the United States,” with a goal to help children by six months. With treatment by that age, they can often reach full hearing, but after that, they’ll suffer permanent language delays.

Nancy M. Young, MD, an otolaryngologist, formed the cochlear implant team at Lurie Children’s Hospital, Chicago/Northwestern in 1991 and has done 2,500 pediatric implantations since then.

“Cochlear implantation is quite miraculous and quite transformative in the lives of deaf children and adults,” Young said. “If you look at the brains of normal hearing children and compare them to those with hearing loss, you can see how hearing loss affects the brain.”

In addition to 30 audiologists, surgeons and speech language pathologists, Young’s team includes an educator and a social worker. “These two are very, very important,” she said. “They’re able to provide support to families and address barriers.”

Such support is critical to “helping each child achieve their full potential,” she said.

Similarly, at UCSF, Chan and his team have found that some parents have the means to ensure their child gets treated, while many other parents don’t have the resources to make appointments and get the necessary care. A graduate student working with him developed “human-centered design to solve this problem,” he said, helping to “support families in their communities so they can make it to appointments without worrying about putting food on the table.”

When UCSF provided a patient “navigator,” patients saw immediate improvements, he said, with many more children making it to appointments and “having a positive outcome that will reverberate the rest of their life.”
 

“Just as there is so much heterogeneity in the genetic cause of hearing loss, there's so much heterogeneity in the social factors that are leading to differential outcomes, and these need to be identified,” Chan said. “We think that human-centered care navigation can provide a general framework for identifying these and to be able to provide precision care for our children.”

Chan’s hopefulness that looking at diseases from all angles can help be a force for good in people’s lives was echoed throughout the symposium, most notably when Gini Deshpande channeled the positivity of her late husband Atul Butte.

Butte was known for his unbridled optimism and his faith in technology, and Deshpande echoed those sentiments. “Technology will provide solutions to what we need,” she said. “We’re already bringing technology into molecular tumor boards. We can use it to bring expertise to patients with rare cancers.”