NGF Blog


Advances in Gene Therapy for Gaucher Disease

Gaucher disease involves a genetic mutation that causes a build-up of the fatty chemical glucocerebroside. Current Gaucher disease treatment options create workarounds to help your body cope with excess glucocerebroside:

But there is a third treatment option on the horizon called gene therapy.

What Is Gene Therapy?

The goal of gene therapy is to permanently correct the genetic problem at the heart of Gaucher disease. One way to accomplish this goal is through gene augmentation (also called gene addition or gene transfer), which adds a functional copy of the gene to your body.

Sarah Neuhaus, DO, senior medical director of clinical development for Prevail Therapeutics, compares gene transfer to replacing a flat tire. “You still have the flat tire in your trunk,” she says, “but you are replacing it with another fully formed object that can do the job.”

Prevail Therapeutics and other biotechnology companies are working to develop a gene therapy that successfully treats Gaucher disease. Disorders caused by a single genetic mutation, including Gaucher disease, are excellent targets for gene therapy approaches, such as gene transfer.

While all these companies share a common goal, their approaches to gene therapy for Gaucher disease differ. Prevail delivers the therapy “in vivo” (in your body) through IV infusion. They use an adeno-associated virus (AAV) as their vector (a deactivated virus that carries the therapy throughout your body). AAV is a common delivery tool used for gene therapies. Scientists change the AAVs used for gene transfer so they cannot replicate inside the human body and are no longer a viral threat. AAV delivery allows the healthy gene to function in your body long term.

Q&A With Prevail on Gene Therapy for Gaucher Disease

We spoke with Dr. Neuhaus to better understand gene therapy for Gaucher disease, Prevail’s approach, and how gene therapy has progressed since our 2020 article: Gene Therapy for Gaucher Disease, AAV, Lentivirus, & More. Here’s how she answered our questions:

NGF: Why consider gene therapy for Gaucher disease when ERT & SRT are available?

Dr. Neuhaus: Available Gaucher disease treatments improve clinical outcomes, patient survival, and quality of life for people with Gaucher disease. But they have limitations.

What we hear time and time again is that bi-weekly ERT infusions can be restrictive. In extreme situations, ERT can prevent someone from traveling because of their health insurance, physician, or facility. It’s often an access issue. The hope and promise of gene therapy is that it could just be a one-time therapy that would alleviate the need for bi-weekly treatments.

Gene therapy might also be attractive if you don’t get an optimal response from your ERT or SRT. Despite therapy, you may still have:

If you experience one of these “four criteria of suboptimal response,” you may be eligible to try gene therapy.

NGF: Will gene therapy address symptoms that ERT and SRT cannot treat?

Dr. Neuhaus: The two areas in the human body that ERT does not handle well are penetrating the bones and crossing the blood-brain barrier to reach the brain. Gene therapy could potentially address those issues by expressing a healthy copy of the gene. Animal studies have tested this gene therapy approach. The studies showed that AAVs delivered intravenously can bring the healthy copy of the gene to the bone marrow to produce glucocerebrosidase. Certain AAVs can even cross the blood-brain barrier and potentially provide a central nervous system replacement.

Active Phase 1 trials are currently enrolling. These trials are our first opportunity to assess how gene transfer works for people living with Gaucher disease type 1. As expected for clinical trials that are first-in-human, the data we have at this time is not based on human evidence—rather, it’s built from animal models. We don’t have enough data in human patients yet, but that is still the promise and the hope of these modalities.

NGF: How does Prevail’s gene therapy for Gaucher disease differ from gene therapy for other diseases?

Dr. Neuhaus: Several ongoing clinical trials using AAV-associated gene replacement aim to treat neuromuscular disorders. One such disorder is Duchenne muscular dystrophy (DMD)—there are several ongoing clinical trials utilizing gene therapies for this and other neuromuscular disorders. In these conditions, gene therapy is delivered as an IV infusion and goes throughout your body (systemic), similar to the route of delivery used for Gaucher disease type 1.

Gene therapies for neuromuscular disorders have a muscle-specific gene promoter to target muscle tissue, which is the region of the body affected in diseases like DMD. The muscle-specific promoter helps the gene therapy “turn on” in those desired skeletal muscle cells.

Gaucher disease, unlike neuromuscular conditions, affects many different organ systems and tissues in the body. For this reason, we don’t want to limit the cell types where Gaucher disease gene therapy is able to “turn on.” The goal is for the gene therapy to activate in multiple cell types. So our gene therapy for Gaucher disease uses a promoter that is not specific to one cell type, such as skeletal muscle. That is by design. It activates in multiple cell types because we want gene therapy to work in multiple organs, such as the liver or the spleen.

NGF: Has there been recent progress in gene therapy for Gaucher disease?

Dr. Neuhaus: Because Gaucher is a rare disease and the patient population is small, trials are still evolving, and the data is maturing. Studies are ongoing and currently enrolling; however, there haven’t been any recent therapeutic approvals related to gene therapy specific to Gaucher disease.

Despite this, we continue to learn more by studying other AAV-based gene therapies approved for other conditions, such as hemophilia. We also continue to learn more about immunology—how a patient’s body responds to gene therapy and the deactivated virus (called a vector) that carries the therapy throughout the body.

Different trials use different AAV-vectors, and based on a person’s immunological status, some people may have antibodies to a specific vector that would potentially prevent them from participating in that trial.

We’re trying to understand the importance and role of immunology. Researchers are working hard to understand immunological responses to make this therapy as broadly available as possible while keeping it safe. We want everyone interested in gene therapy to be eligible.

NGF: Which Prevail clinical trials for gene therapy and Gaucher disease are recruiting?

Dr. Neuhaus: Prevail’s gene therapy trials differ from other available clinical trials because they rely on a different methodology. For gene therapy using an in-vivo AAV-based approach, Prevail has three trials in progress for people living with Gaucher disease:

PROCEED: People with type 1 Gaucher disease

This phase 1/2 trial is recruiting people ages 18 to 65 with type 1 Gaucher disease. Participants need to be in stable condition and receiving a safe dose of ERT or SRT for two years or more. Eligible candidates must have one of the four criteria of suboptimal response to their treatment, which include ongoing:

  • Bone symptoms
  • Liver enlargement
  • Low platelets
  • Spleen enlargement

You’ll remain on your baseline treatment (ERT or SRT) for three to nine months following gene therapy. Continuing with your current treatment after receiving gene therapy ensures maximum safety. We taper off your ERT and SRT as we continue to monitor how your body responds to the gene therapy.

PROVIDE: Infants with type 2 Gaucher disease

This is an active and ongoing phase 1/2 trial for infants diagnosed with type 2 Gaucher disease. It’s offered at four sites (three in the United States and one in the United Kingdom). Several patients have already received the therapy, but the trial still accepts patients globally. Type 2 Gaucher disease is a very severe condition, with high morbidity and mortality.

PROPEL: People with a GBA1 mutation and Parkinson’s disease

Carriers of Gaucher disease with a GBA1 mutation and a diagnosis (or symptoms) of Parkinson’s disease may be eligible for this phase 1/2a trial. Learn more about the potential link between Parkinson’s disease and Gaucher disease.

NGF: How soon can we expect gene therapy to be an approved and viable treatment option for Gaucher disease?

Dr. Neuhaus: Gene therapy follows a unique clinical development path that depends on the indication and strength of the data.

The FDA requires that gene therapy studies follow patients for five years. The first 12 to 24 months are the most important benchmarks for us to gather biomarker data, imaging data, and, most importantly, clinical functional data. How is the patient doing? How are they feeling? How are they responding? We look at safety and what we’re able to measure in patients with Gaucher disease type 1, such as their:

  • Blood counts
  • Platelet count
  • Liver size
  • Spleen size

Our clinical studies follow all study participants for five years but Prevail continues to do everything we can to move clinical development more quickly. We will continue to have ongoing discussions with the FDA, once we reach key milestones in the study, but only time and the data will tell.

The data needs to be impressive and, importantly, show that the therapy is safe. Enrolling clinical trials can sometimes be challenging because the trials can only move as quickly as patients enroll. But patients will often prefer to enroll once there is data and evidence of safety and efficacy.

In another year or two, we may have more concrete data to show preliminary results from this trial. Then, patients can make a data-driven decision to choose this method because they see the results, the patients who have experienced it, and the durable effect. And unfortunately, we’re not in that position with data in hand right now.

In the meantime, we want to work hand-in-hand with trial participants to expedite things and limit disruptions to their lives, while also being safe and accurate.

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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