Having worked for decades to improve the lives of children with rare diseases, Hudson Freeze is still on the case.

Hudson Freeze, PhD is not your average researcher. His work focuses on congenital disorders of glycosylation, or CDG, a severe group of diseases that affect fewer than 2,000 children worldwide. Those conditions occur when sugar molecules on many of our proteins are absent or incomplete. That can lead to serious, often fatal, malfunctions in various organ systems throughout the body.

Although Freeze is not a clinician, he is deeply involved in identifying these rare CDG mutations, and providing families with answers to what is often a challenging diagnosis. Because CDG is a group of incurable diseases, families of children with CDG reach out to Freeze almost weekly, seeking help.

“If someone asks for help, I say, ‘Let me try,’” says Freeze. “Any glimmer of hope is a path worth pursuing, anything to make life easier for children with CDG.”

Freeze has been working on CDG for more than 25 years and has worked with more than 300 patients, and he has kept in touch with many of them over the years.

“Not a day goes by when I don’t think of them and their struggles—but mostly their smiles,” says Freeze. “It’s the reason we won’t give up on trying to understand them and maybe even finding treatments.”

Treating disease with sugar
Although CDG presents as permanent and irreversible mutations, Freeze’s research has been instrumental in discovering an approach to alleviate severe symptoms of CDG—such as seizures—in certain patients. The answer: sugar. Thanks to Freeze and others, there are about 30 patients worldwide who are now taking mannose, a simple sugar molecule, to help alleviate their CDG symptoms.

Today, the strategy of treating diseases with simple sugar molecules is being explored in other glycosylation disorders, as well as less-rare diseases such as multiple sclerosis, cancer and diabetes.

Rare Disease Day at Sanford Burnham Prebys
Freeze’s impact on the lives of families living with CDG extends well beyond the walls of his lab. Since 2010, he has organized an annual Rare Disease Day Symposium each February, where scientists, doctors and families gather from around the world to discuss the latest research and meet other families coping with rare diseases. Last year, the pandemic forced the Institute to press pause on the event, but this year, Rare Disease Day is back in San Diego and stronger than ever.

“It’s a chance for the global CDG community to come together, support one another and continue to put our heads together to find treatments,” says Freeze. “It’s always my favorite weekend of the year, and I’m thrilled that we’re able to do it again safely.”

The 2022 Rare Disease Day Symposium & CDG/NGLY1 Family Conference will take place February 25–27 at the Dana on Mission Bay Resort in San Diego. Scientific sessions will be held on the 25th and 26th, and the Family Conference will take place on the 27th.

Register Here

11-year-old Damian Omler is the only known individual with his CDG mutation.

Donnie and Gracie Omler are used to the question, “What’s wrong with your son?” Now, they don’t have to say, “We don’t know.”

While the Omlers knew that something was off when their son Damian started to miss his early milestones—he struggled to sit up, make “goo-goo” sounds and put weight on his legs—a decade passed before they had an official diagnosis.

Doctors suspected Damian had a congenital disorder of glycosylation, or CDG, but couldn’t confirm the mutation type. The family began attending Sanford Burnham Prebys’ Rare Disease Day Symposiums, but unanswered questions made them unsure of how they fit into the CDG community.

Now, the Omler family has answers. Hudson Freeze, PhD, and his team determined that Damian has a never-before-seen type of CDG, now named CDG-GET4. This gene codes for a chaperone protein that guides other proteins to where they need to be in a cell. Freeze’s team found that in Damian’s case, one of these chaperone proteins was almost completely gone.

The Omler family shared with KPBS how receiving answers changed their life.

“After the diagnosis we sat and smiled for a long time,” says Donnie. “Obviously we are not done. But answers give us hope. There might be a treatment or supplement for Damian. We might be able to predict possible complications in the future.”

Today, Donnie and Gracie focus on giving Damian a fulfilling life. He attends school, where he has friends and participates in sports. He plays with his 9-year-old brother, DJ. He loves rock music—and even attempted to strum a guitar recently. Donnie, a rock lover himself, clutches his heart with joy when describing this development.

Still, the Omlers recognize the challenges that Damian faces. He has seizures, needs help using the restroom and recently got a feeding tube. They attend the Institute’s symposiums to make sure they are up-to-date on information that might help Damian. They also fundraise as much as possible to help researchers do more.

“We are amazed at how much brainpower it takes to find a diagnosis, let alone treat the disease,” says Donnie. “There is no way we could have done this alone. Without these scientists, we would probably still be waiting for answers.”

This year’s event centered on CDG, a rare genetic condition that affects around 1,500 people worldwide.

With more than 270 attendees and 30 world-renowned scientists and clinicians, Sanford Burnham Prebys’ 11th Annual Rare Disease Day Symposium was officially the largest in the event’s history. This year’s discussion centered on congenital disorders of glycosylation, or CDG, a rare genetic condition that affects around 1,500 people worldwide.

Malin Burnham, T. Denny Sanford and Debra Turner, honorary trustees of Sanford Burnham Prebys, opened the three-day meeting with moving remarks. A theme emerged: Medical advances are accelerated when key stakeholders work together—including scientists, physicians, people with CDG and their families, patient advocacy groups, granting agencies, industry and philanthropists.

“Our annual symposium aims to create an ecosystem in which key stakeholders can collaborate and communicate,” said Hudson Freeze, PhD, director of the Human Genetics Program at Sanford Burnham Prebys and symposium chair. “Together, we celebrate our successes, focus on challenges and discuss the future of CDG research.”

Presenters at the meeting described the power of the ecosystem. Since the first conference a decade ago where scientists reported on the basic biology of CDGs, today we have promising clinical trials for the most common CDG mutation. In addition, a historic nationwide effort to establish the natural history of CDGs launched this year—which addresses decades of unresolved questions and helps remove barriers to starting clinical trials.

First discovered in the 1990s, scientists now know that CDG is caused by mutations that disrupt the body’s normal process of attaching sugars to proteins. Children with CDG have varying degrees of speech and language difficulty, poor balance, motor control, vision problems, hearing impairments and seizures. 

Because CDG is rare, many patients bounce between doctors and clinics for years before they receive an accurate diagnosis. At the symposium, an innovative session called the “Doctor-is-in” session connects families with medical researchers and clinicians in small groups. For some medical researchers, the session is the first time they have met a person with CDG.

The conference was co-organized by Sanford Burnham Prebys and CDG CARE, a nonprofit organization founded by parents seeking information and support for CDG.

The unofficial theme of Sanford Burnham Prebys’ 10th annual Rare Disease Day symposium can be summarized in one word: hope. 

This year’s event focused on rare bone disorders and bone cancers, with a special emphasis on a condition called multiple hereditary exostoses (MHE) that causes numerous bone tumors in children. Until now, children with MHE had only one treatment option: repeated surgeries to remove these tumors. 

Now, the first medicine, called palovarotene, that may be able to slow or halt this bone growth is being tested in a clinical trial—potentially saving these children from a lifetime of painful surgeries. Yu Yamaguchi, MD, PhD, symposium chair and professor in Sanford Burnham Prebys’ Human Genetics program, participated in the key research needed in order for the clinical trial to begin.

“For the first time, a diagnosis doesn’t feel like a life sentence,” says Greta Falkner, who attended the symposium with her 8-year-old son, Jackson Falkner. Jackson has MHE and has undergone 13 surgeries to date. “Today we have hope for a cure.”

The launch of a study evaluating palovarotene as an MHE treatment is the result of decades of hard work and collaboration between scientists, clinicians, Clementia Pharmaceuticals (now Ipsen) and the MHE Research Foundation—a patient advocacy and support group. 

The symposium featured an all-star lineup of distinguished speakers in the field of skeletal biology and MHE research, including keynote speaker Henry Kronenberg, MD, of Massachusetts General Hospital and Maurizio Pacifici, PhD, of Children’s Hospital of Philadelphia, whose research formed the scientific rationale for the use of the drug in MHE. The event was sponsored by the MHE Research Foundation and Clementia Pharmaceuticals. 

“We are so grateful that Sanford Burnham Prebys holds this Rare Disease Day symposium to bring together all the important players in rare disease drug discovery: scientists, doctors, families and drug companies. It is literally ‘bench to bedside’ at one event,” says Sarah Ziegler, who co-founded the MHE Research Foundation with Craig and Susan Eaton after Sarah’s son was diagnosed with MHE in 1993 (when little to no information was available on the disease). “Foundations like ours rely on the research of scientists like Drs. Yamaguchi and Pacifici to find new medicines for patients—and the arrival of the first potential treatment for MHE is the perfect example of the power of this research.” 

Multiple parents and children with MHE, some of whom are enrolled in the clinical trial, attended the event. For most of these children, this was the first time they’d met another person with their condition. 
 

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