Migalastat, known by its brand name Galafold, is an oral medication for a specific genetic condition. It works to address underlying cellular issues and is available as an oral capsule.
What Migalastat Is and How It Works
Migalastat (brand name Galafold) is an oral medication used for Fabry disease, a rare genetic disorder. Fabry disease stems from a deficiency of the alpha-galactosidase A (alpha-Gal A) enzyme, which is encoded by the GLA gene. This enzyme normally breaks down a fatty substance called globotriaosylceramide (Gb3). Its deficiency leads to Gb3 accumulation in various cells and tissues, including blood vessels, kidneys, nerves, and the heart.
Migalastat functions as a “pharmacological chaperone,” helping the body’s own dysfunctional alpha-Gal A enzyme. It works by reversibly binding to the active site of certain mutated forms of the alpha-Gal A protein. This binding stabilizes the enzyme, helping it to fold correctly and allowing it to move from the endoplasmic reticulum to the lysosome, where it can then break down accumulated Gb3.
Once in the lysosome, migalastat dissociates from the alpha-Gal A enzyme. This allows the enzyme to become active and perform its function of breaking down Gb3. This mechanism is specific, only effective in patients whose GLA gene mutations allow the alpha-Gal A enzyme to respond to this chaperone effect.
Who Can Be Treated with Migalastat
Migalastat is not suitable for all individuals with Fabry disease; it is specifically approved for adults and adolescents, those aged 12 years and older, who have certain “amenable” mutations in the GLA gene. An amenable mutation refers to a genetic change that allows the alpha-Gal A enzyme to respond to migalastat’s chaperone effect, meaning the enzyme, though misfolded, retains some enzymatic activity.
Genetic testing is necessary to determine if a patient has an amenable mutation. Healthcare professionals rely on specific lists of amenable mutations to confirm eligibility for treatment. It is estimated that approximately 35% to 50% of Fabry patients may have amenable GLA gene variants.
Beyond genetic amenability, healthcare providers also consider other factors, such as kidney function. Migalastat is not recommended for patients with severe renal impairment.
Taking Migalastat: Dosage and Administration
Migalastat is administered orally as a 123 mg capsule. The dosage regimen is one capsule taken once every other day, ideally at the same time. Consistency in dosing helps ensure optimal benefits.
Take migalastat on an empty stomach. Patients should not consume food for at least two hours before and two hours after taking the capsule. Clear liquids, such as water or carbonated drinks, are permissible during this fasting window.
The capsules must be swallowed whole and should not be cut, crushed, or chewed. If a dose is missed, it should only be taken if it is within 12 hours of the regularly scheduled time. If more than 12 hours have passed, the missed dose should be skipped, and the patient should resume the every-other-day dosing schedule at the next planned time.
Potential Side Effects and Important Considerations
Patients taking migalastat may experience side effects. Common reactions include headache, nausea, nasopharyngitis (cold symptoms), and urinary tract infections; other potential side effects include dizziness, diarrhea, muscle pain, and fatigue.
Discuss any side effects with your healthcare provider. Regular monitoring by a healthcare professional is also advised for patients on migalastat. This monitoring may include periodic assessments of renal function, cardiac evaluations, and enzyme activity levels.
While there are no specific contraindications listed for pregnancy or breastfeeding, pregnant or breastfeeding individuals should consult their doctor to weigh the benefits and risks. Continuous medical supervision is necessary to manage treatment effectively and safely.