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a phase 3 trial of sebelipase alfa in lysosomal acid lipase
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A phase 3 trial of sebelipase alfa in lysosomal acid lipase deficiency
Cause
Conclusion
The disease is caused by an enzyme deficiency due to mutations in the acid lipase gene (LIPA), located in a specific region of chromosome 10 (10q24-q25).
In conclusion, cirrhosis and severe dyslipidemia often develop at an early age in patients with lysosomal acid lipase deficiency.
Pros and cons
Diagnosis
There are no pros
The diagnosis is confirmed by the genetic test of the LIPA gene or by an examination showing the deficiency of the lysosomal acid lipase (LAL) enzyme activity in blood leukocytes, in skin fibroblasts or in dried blood spots.
Cons:
- Hepatomegaly
- In severe cases, children develop cirrhosis and chronic liver failure
- Vomiting
- Diarrhea
- Calcium deposits in the adrenal glandsomiting
Applications in medicine
The use of enzyme substitution therapy using the enzyme sebelipase alfa (Kanuma) lowers lipid values (such as triglycerides and cholesterol) in the blood, improves symptoms such as liver problems, and increases life expectancy. Its use has been approved in the United States and in Europe. Treatment with seblipase alfa is performed through an intravenous infusion once a week in patients with severe LAL deficiency (Wolman's disease), and once every two weeks in all other patients. With this treatment a protein called rhLAL is provided which replaces the LAL enzyme.
Sebelipase alfa
Sebelipase alfa is a recombinant human lysosomal acid lipase (rhLAL). Sebelipase alfa binds to cell surface receptors by means of glycans expressed in the protein and is subsequently internalized in lysosomes. It catalyzes the lysosomal hydrolysis of cholesterol esters and triglycerides in free cholesterol, glycerol and free fatty acids.
Applied in Ecuador
Definition
The allogeneic transplantation of hematopoietic progenitors (bone marrow or umbilical cord) has been used anecdotally, which prevents the deadly course of the disease but not the appearance of organ-specific complications such as liver cirrhosis. Recently, sebilipase, an enzymatic treatment that replaces the lysosomal acid lipase deficit, has been commercialized. One of the limiting factors for the use of substitute enzymatic therapy is its high cost, which exceeds $ 200,000 per year.
Lysosomal acid lipase deficiency
Deficiency of lysosomal acid lipase (LIPA) is a metabolic fluid storage disease that can occur in two ways:
- Wolman's disease - The most severe form that begins early in childhood with accumulation of fat (lipids) in most tissues of the body.
- Storage disease of cholesterol esters