By Counterforce Health Team —

Galafold: A Targeted Therapy for Fabry Disease

Fabry disease is a rare, inherited disorder caused by mutations in the GLA gene, which lead to a deficiency of the enzyme alpha-galactosidase A (α-Gal A). Without enough of this enzyme, a fatty substance called GL-3 (globotriaosylceramide) builds up in cells throughout the body — particularly in the kidneys, heart, skin, and nervous system.

This buildup causes a wide range of symptoms, including pain, fatigue, kidney problems, heart disease, and gastrointestinal issues.

For many years, enzyme replacement therapy (ERT) was the only available treatment for Fabry disease. But in 2018, a new oral therapy called Galafold® (migalastat) was approved by the U.S. Food and Drug Administration (FDA), offering an alternative approach for certain patients.

What Is Galafold?

Galafold (migalastat) is a prescription oral medication used to treat adults with Fabry disease who have a confirmed “amenable” GLA gene mutation.

“Amenable” means the specific genetic mutation can respond to migalastat — the medication works only for certain mutations that can be “stabilized” by the drug.

Unlike enzyme replacement therapy, which supplies an external form of the missing enzyme, Galafold helps the body’s own enzyme work better. It’s taken as a capsule by mouth every other day, making it a convenient and non-invasive treatment option.

Understanding Fabry Disease

Fabry disease is an X-linked lysosomal storage disorder — meaning it’s caused by a gene mutation on the X chromosome and affects the cell’s lysosomes (the “recycling centers” that break down waste).

When α-Gal A doesn’t function properly, GL-3 accumulates inside cells, leading to:

  • Pain and burning sensations in hands and feet (acroparesthesia)
  • Skin lesions called angiokeratomas
  • Kidney problems (proteinuria, reduced kidney function)
  • Heart issues (thickened heart muscle, arrhythmias)
  • Digestive symptoms (cramps, diarrhea)
  • Fatigue, dizziness, or hearing loss

Over time, Fabry disease can cause serious complications if left untreated.

How Galafold Works

Galafold acts as a pharmacological chaperone — a small molecule that helps stabilize and guide the body’s own enzyme so it can function correctly.

Here’s how it works:

  1. Some GLA mutations cause the α-Gal A enzyme to be misfolded, meaning it can’t reach its proper location in the cell.
  2. Galafold binds to and stabilizes the misfolded enzyme.
  3. This stabilization allows the enzyme to travel to the lysosome, where it can break down GL-3 effectively.
  4. As a result, GL-3 levels decrease, reducing damage to tissues and organs.

Essentially, Galafold “rescues” the patient’s own enzyme, allowing it to work as intended — but only if the enzyme is capable of being stabilized (i.e., the mutation is amenable).

Who Can Take Galafold

Galafold is approved for adults (18 years and older) with a confirmed diagnosis of Fabry disease who have an amenable GLA mutation.

Before starting treatment, a genetic test is required to confirm that the patient’s mutation is responsive to migalastat. The FDA and manufacturer provide a list of known amenable mutations.

Galafold is not effective for individuals with non-amenable mutations, as their enzymes cannot be stabilized by this therapy.

How Galafold Is Taken

  • Form: Oral capsule (123 mg migalastat)
  • Dosage: One capsule every other day, swallowed whole with a glass of water
  • Timing: Should be taken on an empty stomach — at least 2 hours before and 2 hours after eating (a total of 4 hours without food).

Consistency is key: taking Galafold at the same time every other day helps maintain stable enzyme activity.

Clinical Evidence and Effectiveness

Galafold’s approval was supported by several clinical trials, including the FACETS and ATTRACT studies.

Key findings:

  • In patients with amenable mutations, Galafold significantly reduced GL-3 accumulation in kidney cells.
  • Kidney function remained stable over time in most participants.
  • In the ATTRACT trial, Galafold was found to be comparable to enzyme replacement therapy (ERT) in maintaining kidney function — with the added benefit of oral dosing.
  • Cardiac structure (heart wall thickness) improved in some patients after long-term use.

These results showed that Galafold is an effective alternative for eligible patients, with similar outcomes to ERT and the convenience of oral administration.

Benefits of Galafold

  • Oral therapy — no infusions or needles required
  • Targets the underlying enzyme defect rather than just replacing it
  • Comparable efficacy to enzyme replacement therapy in eligible patients
  • Improved convenience and flexibility in daily life
  • Fewer infusion-related side effects (since it’s taken by mouth)

For many adults with Fabry disease, Galafold provides a more manageable and less invasive way to maintain treatment.

Possible Side Effects

Galafold is generally well tolerated, but side effects can occur.

Common side effects:

  • Headache
  • Nausea
  • Stomach pain
  • Fatigue
  • Cough
  • Dizziness

Less common side effects:

  • Heart palpitations
  • Flu-like symptoms
  • Mild increases in kidney markers (like creatinine)

If any severe reactions or new symptoms occur, patients should contact their healthcare provider.

Monitoring During Treatment

Doctors will regularly monitor:

  • Kidney function (creatinine, protein levels)
  • Heart health (ECG or echocardiogram)
  • GL-3 and lyso-Gb3 levels in blood or urine
  • General symptoms and quality of life

Regular follow-ups help ensure that Galafold is effective and well tolerated.

Practical Considerations

  • Missed dose: If you miss a scheduled dose, take it as soon as you remember — unless it’s within 8 hours of your next dose. Do not double up.
  • Storage: Store at room temperature in the original blister packaging.
  • Diet: Take on an empty stomach (2 hours before and after meals).
  • Interactions: Tell your doctor about all medications, supplements, or herbal products you take.

The Bottom Line

Galafold (migalastat) represents an important step forward in the treatment of Fabry disease — offering an effective, oral alternative to enzyme replacement therapy for patients with amenable mutations.

By stabilizing the body’s own enzyme rather than replacing it, Galafold provides a targeted, convenient, and patient-friendly approach to managing this lifelong genetic condition.

For those who qualify, Galafold offers not just medical benefit but also freedom — the freedom to treat Fabry disease without the burden of biweekly infusions.