In February 2018, attendees from around the world met in San Diego for the 14^th annual WorldSymposium, a research conference focused exclusively on the latest discoveries related to lysosomal diseases. Doctors and scientists met for three days to present and discuss cutting-edge research findings that may help change the diagnostic and treatment process for a variety of lysosomal diseases, including Gaucher disease.

In the first few years, only a handful of people attended WORLDSymposium. The first conferences had a strong emphasis on research related to Gaucher disease. But this year, the symposium hosted about 1,800 participants, highlighting discoveries related to other rare diseases, such as Pompe disease and mucopolysaccharidoses.

Even though the symposium expanded to include more lysosomal diseases, Gaucher disease remains an important topic of conversation among conference participants. This year, researchers presented approximately 55 research paper abstracts, posters, and presentations related to Gaucher disease. Conference participants, including research teams from universities, pharmaceutical corporations, and biotechnology companies, presented basic science, translational, and clinical trial research results. Dr. Ellen Sidransky, senior investigator at the National Human Genome Research Institute, part of the National Institutes of Health, found two of these topics especially intriguing…and could eventually be key to helping people living with Gaucher disease achieve better health.

Biomarkers as Diagnostic Tools

By definition, biomarkers are any measurable substance in a person that is used to identify the presence of diseases, infections, or exposure to materials in the environment. For several years, scientists have explored ways to use unique human biomarkers to indicate the presence or severity of Gaucher disease.

At the 2018 WORLDSymposium, research teams from Israel and Germany presented results examining the relationship between the lipid glucosylsphingosine (lyso-Gb1) and specific genetic mutations resulting in Gaucher disease. Using lyso-Gb1 as a biomarker, scientists identified a correlation between the lipid and the clinical severity of Gaucher disease. Further, for people living with type 1 Gaucher disease resulting from the N37OS genetic mutation, levels of lyso-Gb1 could also reliably predict response to treatment with low-dose enzyme replacement therapy (ERT).

In a separate presentation, researchers from Germany presented results from a 4.5 year study examining levels of the same biomarker, lyso-Gb1, in more than 2,800 people. Scientists measured blood samples from study participants for levels of lyso-Gb1, showing the higher the concentration of lyso-Gb1 in blood samples, the more severe the genetic mutations resulting in Gaucher disease. Of the 2,800 people included in the study, scientists identified 911 individuals as either having Gaucher disease or being Gaucher disease carriers, indicating this biomarker may also be useful in diagnosing Gaucher disease.

In the future, screening for lyso-Gb1 blood levels could aid in early diagnosis and disease management. “It’s possible that testing for levels of lyso-bL1 in future Gaucher disease screening measures could help guide treatment decisions, including the timing of treatment, the dosing of enzyme replacement therapy, and the monitoring of how people respond to their treatment,” says Dr. Sidransky.

If research continues, screening tests could be used to help anticipate the challenges each individual may face in the course of his/her disease. Eventually, screening tests for biomarkers, like lyso-Gb1, may help tailor treatment to find the most effective therapies possible. While effective treatment using ERT has been available for more than 15 years, screening tests predicting the severity of an individual’s Gaucher disease and their response to certain treatments are not yet available in healthcare settings.

Treatment Using Saposin C Nanovesicles

With increased interest in precision medicine and more personalized treatment options, scientists are exploring the use of microscopic containers, or nanovesicles, to deliver targeted therapies directly to certain body tissues. In the future, these types of treatments may help eliminate the need for more invasive procedures, promoting better outcomes due to more precise delivery of treatment.

One of the translational research talks at WORLDSymposium described a novel approach to treating neuronopathic (Type 2 &3) Gaucher disease using nanovesicles small enough to travel through the bloodstream. For people living with Gaucher disease, insufficient amounts of the enzyme glucocerebrosidase (GCase) make their way into the tissues. As a result, the lipid glucocerebroside builds up in body tissues causing symptoms of Gaucher disease. But in healthy individuals, a certain protein, called saposin C (SapC), helps activate GCase in the body. This activation promotes the breakdown of the lipid glucocerebroside. While ERT successfully reverses the lipid accumulation in many organs, it does not enter the brain and thus does not help the brain involvement in neuronopathic Gaucher disease.

Using nanovesicles created from SapC and a lipid called dioleoyl phosphatidylserine (DOPS), scientists delivered GCase directly to the brains of a mouse model of Gaucher disease. Compared to mice that received GCase using more traditional methods, GCase delivered to the brain inside SapC-DOPS nanovesicles showed up to 15 times more activity for as long as 48 hours.

“This is a different way to target treatment for Gaucher disease,” Dr. Sidransky says. “If further research provides similar results, delivering GCase directly to the brain using nanovesicles might become a promising new treatment strategy for both neuronopathic Gaucher disease and other lysosomal storage disorders with brain involvement.”

While research presented at WORLDSymposium hasn’t been incorporated into mainstream medical care, the results offer an encouraging glimpse into future diagnostic and treatment options for Gaucher disease. Researchers can use this information to identify additional areas of investigation necessary to further our understanding of Gaucher disease, develop innovative diagnostic and treatment options, and offer hope to each person affected by lysosomal diseases.