NGF Blog


Gaucher Disease Treatment: What’s on the Horizon?

A bright future lies ahead with Gaucher disease treatment developments.

Gaucher disease treatment has come a long way in the past three decades. The United States Food and Drug Administration (FDA) approved the first enzyme replacement therapy (ERT) in 1991. That first approval opened the door for other ERT treatments and paved the road for substrate reduction therapy (SRT).

But advances in science help researchers continue to learn more about Gaucher disease and work toward new advances in treatment. For a peek into those advances, we turned to Pramod Mistry, MBBS, PhD, MA, MD, director of the Yale Lysosomal Disease Center and Gaucher Disease Treatment Center.

Dr. Mistry is a member of the National Gaucher Foundation’s Medical Advisory Board. He is the recipient of several awards for his work on Gaucher disease. His research and writing contributed significantly to our understanding of the biomarkers, disease processes, and therapies associated with Gaucher disease.

“I have never been more inspired about the treatment prospects for people with Gaucher disease,” Dr. Mistry says. “We are entering an era where we have the tools and can take an uncompromising approach to protect patients from disease complications.”

We asked Dr. Mistry about what he sees on the horizon for Gaucher disease treatment. He expects research and developments to focus on four approaches:

1. Using Current ERT Treatments More Effectively

ERT has changed how people live with Gaucher disease. But Dr. Mistry believes that experts still have more to learn about ERT to provide patients with the best possible outcomes.

“Over time, many physicians have adopted the approach that all ERT treatments are the same, and that’s not strictly true,” he says. “These are very distinct enzyme treatments created by different biotechnology approaches. We must capture rigorous data for each ERT and use that as a foundation to create effective treatment plans for patients.”

Dr. Mistry adds that one specific outcome that needs closer inspection is bone crisis. Data shows that outcomes related to the liver, spleen, and blood counts tend to be similar regardless of the patient’s specific ERT. But, there is no hard data about bone outcomes comparing different ERTs.

“Bone crisis can be a life-changing event,” Dr. Mistry says. “We’re asking why, in the era of ERT, some people have bone crisis, and others are well-treated.”

Dr. Mistry believes previously collected data may hold answers to many questions about Gaucher disease and treatment. Researchers are using existing literature, studies, and patient data to learn more about treatment response and the risk of disease severity.

Dr. Mistry was recently part of a research team that used existing data to identify several risk factors associated with the development of bone crisis after ERT treatment. More research is necessary. In this way, continuing to study the collected data on ERT may help physicians personalize existing treatments.

“There is a need to up our game as treating doctors,” Dr. Mistry says. “It’s time to use the the International Gaucher registry and other sources of data to understand what we can and can’t achieve with the treatment and focus on what we can do to improve outcomes.”

2. Addressing Gaucher Disease Gene Mutations

Gene therapy is a promising treatment that could change how some people with Gaucher disease live their lives. The hope is that gene therapy will address the gene mutation at the heart of the disease, offering the prospect of a more permanent solution. Ideally, replacing the affected gene will allow people with Gaucher disease to avoid biweekly ERT infusions and the side effects associated with current treatments.

Although many years of work will need to go into developing a permanent cure for Gaucher disease, Dr. Mistry expects exciting developments in gene therapy techniques, including:

Gene addition

Gene addition (augmentation) involves adding a healthy copy of a mutated gene. It doesn’t remove the genetic defect, but the body could consistently make a high level of enzyme, preventing the up-and-down spikes experienced with ERT.

“There’s still not a lot of evidence, but early trials have begun,” Dr. Mistry says. “It offers hope to patients that there may someday be a one-and-done treatment.”

Gene editing

The approach of gene editing—correcting a gene mutation—is still in the early stages. But Dr. Mistry believes it is the most exciting advancement on the distant horizon for Gaucher disease.

“This technology is truly exciting and may represent a real cure,” he says. “However, there are some big hurdles to overcome. But I’m hopeful that the rate of scientific progress is such that we will witness this big milestone in our lifetimes.”

3. Treating Neuronopathic Gaucher Disease

ERT and SRT offer a better quality of life for many people with Gaucher disease. But those therapies do not cross the blood-brain barrier and can’t treat the neurological symptoms of type 2 and type 3 disease.

“If you look at the global landscape of Gaucher disease,” Dr. Mistry says, “treatment for type 3 Gaucher disease is a huge unmet need.” But researchers are trying to address those concerns.

There are several promising treatment approaches to neuronopathic Gaucher disease in progress:


Researchers are studying a once-daily oral medication, venglustat, to treat adults with type 3 Gaucher disease. Venglustat can enter the brain and may treat neurological symptoms of Gaucher disease. Phase 2 trials showed venglustat—when taken in combination with the ERT Cerezyme (imiglucerase)—is safe and tolerable. Phase 3 trials are in progress.

“In my opinion, venglustat offers the best hope for children with type 3 Gaucher disease,” Dr. Mistry says. “It is built on solid science, we have excellent safety data, and we’ve seen promising clinical trial data so far.”

Gene therapy

Prevail Therapeutics is studying how gene therapy might address neurological symptoms associated with neuronopathic Gaucher disease. Their approach involves delivering a healthy copy of the GBA1 gene through an injection into the area where the brain and spinal cord meet.

They have two ongoing trials:

  • Propel (phase 1/2a) focuses on gene therapy and Parkinson’s disease in people with at least one GBA1 gene mutation.
  • Provide (phase 1/2) studies gene therapy for infants with type 2 Gaucher disease.

Pharmacological chaperone therapy

Pharmacological chaperones are small molecules that bind to faulty proteins to help them work better. Because some pharmacological chaperones can cross the blood-brain barrier, they have become an area of interest for Gaucher disease researchers.

Ambroxol, an expectorant used to clear congestion and relieve throat pain, is a promising pharmacological chaperone for Gaucher disease. Early studies show that high-dose oral ambroxol is well-tolerated and may treat some neurological symptoms of Gaucher disease.

4. Embracing Integrative Medicine and Epigenetic Interventions

At a basic level, Gaucher disease causes systemic inflammation. “Things such as stress, poor sleep, a lack of social enrichment, and not getting enough exercise will trigger more inflammation in the body,” Dr. Mistry says. “And that will make Gaucher disease worse.”

Experts now know integrative medicine and epigenetic interventions, such as dietary changes, mindfulness practices, and physical activity, can help reduce inflammation. Therefore, such interventions may target Gaucher disease symptoms. “These practices and lifestyle choices can also improve your brain health,” Dr. Mistry adds.

He expects these interventions to play a more significant role in Gaucher disease treatment plans, especially as researchers continue to learn more about the connection between Gaucher disease and Parkinson’s disease.

How the National Gaucher Foundation Can Help

If you or a loved one lives with Gaucher disease, the National Gaucher Foundation is here for your family. We offer resources to optimize your health with Gaucher disease and connect you with the support you need.




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