PATIENTs AND FAMILIES Understanding Gaucher Disease

Gaucher disease at a glance

  • Rare, inherited lysosomal disorder in which harmful amounts of fatty materials, or lipids, accumulate in macrophages within tissues in the body1
  • Caused by mutation in a single gene, known as GBA, which makes the protein glucocerebrosidase, or GCase
  • Characterized by toxic buildup of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph)

There are three types of Gaucher disease.

Gaucher disease type 1

  • Affects one in 44,000 people, or around 95 percent of all Gaucher disease cases2
  • Occurs more frequently in people of Ashkenazi Jewish heritage, affecting one in 500 to one in 1,000 individuals in this population3

Gaucher disease type 2

  • Affects fewer than one in 100,000 newborn babies4
  • Associated with severe neurological (brain) involvement4
  • Symptoms develop by age 3 to 6 months4

Gaucher disease type 3

  • Affects one in 100,000 people5
  • Associated with severe neurologic symptoms

AVROBIO is currently developing investigational gene therapies for Gaucher disease type 1, the most common form of the disease, and Gaucher disease type 3.

Gaucher disease symptoms

Gaucher disease type 1

  • Low platelet and hemoglobin counts, leading to easy bruising and bleeding
  • Enlarged liver and spleen
  • Fatigue
  • Bone pain, bone crises (severe episodes of pain caused by reduced blood flow to bones)
  • Other bone problems such as avascular necrosis (death of bone tissue due to a lack of blood supply), osteoporosis, fractures, joint destruction and skeletal abnormalities
  • An adjusted lifetime relative risk of developing Parkinson's disease that may be more than 20 times greater than the general population

Gaucher disease type 2

  • Seizures and spasticity (jerking movements)6
  • Poor ability to suck and swallow6
  • Enlarged liver and spleen6

Gaucher disease type 3

  • Progressive encephalopathy, or neurological disease, which may include memory loss, intellectual disability, developmental delay and seizures7
  • Ophthalmic disorders, including ophthalmoplegia (eye muscle paralysis) and strabismus (cross-eyed)7
  • Systemic manifestations of symptoms common in Gaucher disease type 17
Treating Gaucher disease

The standard of care for Gaucher disease types 1 and 3 is enzyme replacement therapy, or ERT, requiring life-long, biweekly infusions. Substrate reduction therapy, or SRT, is also available for patients with Gaucher disease type 1.

Although ERT and SRT have been shown to improve some of the symptoms of Gaucher disease affecting the body, neither of these treatments impact the neurologic symptoms of Gaucher disease type 2 or 3. Studies have shown that ERT is not effective for relieving necrotic tissue injury (death to tissues), skeletal collapse (death to bone) or tissue fibrosis or scarring.8

Even on the standard of care, people with Gaucher disease types 1 and 3 have a shortened life expectancy9 and may experience debilitating symptoms that significantly reduce their quality of life. Gaucher disease type 2 is unusually fatal, typically causing death before two years of age.7

Learn more about how lysosomal disorders are treated.

At AVROBIO, we are developing a new approach with the goal of halting or preventing Gaucher disease types 1 and 3 with a single administration.

Learn about our investigational gene therapies.

Learn about our clinical trial in Gaucher disease type 1.

What causes Gaucher disease?

Gaucher disease is most often caused by a change in a single gene known as GBA.

The GBA mutation affects production of an enzyme called glucocerebrosidase (GCase).

When the GCase enzyme does not function properly, toxic amounts of the molecules glucosylceramide and glucosylsphingosine build up in the lysosomes, impairing cell function. This leads to the progressive symptoms of Gaucher disease.

How is Gaucher disease inherited?

The general population without Gaucher disease has two copies of the gene that provides the instructional code for making the glucocerebrosidase enzyme.

When one of those copies is a variant gene, the individual is considered a “carrier” of Gaucher disease but will not develop it. When a carrier has a child, he or she has a 50/50 chance of passing the faulty gene to the child.

A child who inherits two variant genes may develop Gaucher disease. Males and females are equally affected.

Gaucher disease inheritance chartGaucher disease inheritance chart

*These links are provided for informational purposes only. AVROBIO is not affiliated with any of these institutions and is not responsible for any of the content on their websites. 

Learn about our clinical trial in Gaucher disease

AVROBIO is conducting a Phase 1/2 study to evaluate the safety and efficacy of our investigational gene therapy for individuals with type 1 Gaucher disease (AVRO-RD-02). The trial is actively recruiting in Canada and Australia. AVROBIO plans to open clinical sites in the U.S.

Learn more

References
  1. National Institutes of Health Genetic and Rare Diseases Information Center. Gaucher disease. https://rarediseases.info.nih.gov/diseases/8233/gaucher-disease. Accessed: October 26, 2020.
  2. Gaucher Disease. Gaucher Disease Type 1. https://www.gaucherdisease.org/about-gaucher-disease/what-is/type-1/. Accessed: November 06, 2020.
  3. Medline Plus. Gaucher disease. https://medlineplus.gov/genetics/condition/gaucher-disease/#synonyms. Accessed: October 28, 2020.
  4. Gauchers Association. Type 2. https://www.gaucher.org.uk/type_2. Accessed: November 6, 2020.
  5. National Institutes of Health Genetic and Rare Diseases Information Center. Gaucher disease type 3. https://rarediseases.info.nih.gov/diseases/2443/gaucher-disease-type-3. Accessed: October 26, 2020.
  6. National Gaucher Foundation. Gaucher disease types 2 and 3. https://www.gaucherdisease.org/about-gaucher-disease/what-is/type-2-3/. Accessed: November 6, 2020.
  7. National Institutes of Health Genetic and Rare Diseases Information Center. Gaucher disease type 3. https://rarediseases.info.nih.gov/diseases/2443/gaucher-disease-type-3. Accessed: October 26, 2020.
  8. US National Library of Medicine National Institutes of Health. Enzyme Replacement or Substrate Reduction? A Review of Gaucher Disease Treatment Options. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981103/. Accessed November 6, 2020.
  9. US National Library of Medicine National Institutes of Health. Life expectancy in Gaucher disease type 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743399/. Accessed November 6, 2020.

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