Immunosuppression Induces Tolerance to Enzyme Treatment in Pompe Disease

Four children not making any acid maltase enzyme tolerated enzyme replacement therapy when also treated with immunosuppressants

Article Highlights:
  • Children with Pompe disease who aren't producing any acid maltase (GAA) enzyme are at risk of immune system rejection of lifesaving enzyme replacement therapy (ERT).
  • A new study reports that treatment with a combination of immunosuppressant drugs prevented or reversed immune system rejection of ERT in four children with Pompe disease.
  • Genzyme is conducting a small study of how to induce tolerance to its ERT drug Myozyme.
by Margaret Wahl on January 16, 2012 - 6:00am

Editor's note 2/2/12: This story was updated to reflect the award of a  new MDA grant to Eric Sjoberg at Amicus Therapeutics.

Drugs that suppress the immune system can successfully prevent or reverse rejection of enzyme replacement therapy in Pompe disease (acid maltase deficiency), a new study has shown.

Pompe disease results from a deficiency of the enzyme acid maltase, also called acid alpha-glucosidase, or GAA. The disease can be treated with Myozyme or Lumizyme, which are both laboratory-modified forms of GAA. Enzyme replacement therapy (ERT) can be lifesaving in the infantile-onset form of Pompe disease.

However, in some individuals, particularly those who are not making any GAA at all, the immune system regards the replacement enzyme as foreign and develops immune system proteins called antibodies that limit the treatment's effectiveness.

Rituximab, methotrexate, IVIG induced immune tolerance

In the January 2012 issue of Genetics in Medicine, Yoav Messinger at Children's Hospitals and Clinics of Minnesota, and colleagues, show that two immunosuppressant drugs — rituximab and methotrexate — prevented formation of anti-GAA antibodies in two children who were not making any GAA themselves and who were being treated with Myozyme.

The investigators also showed that these two drugs, in combination with intravenous immunoglobulins (IVIG), which modify the behavior of the immune system, were effective in reversing an established immune response to Myozyme in two other children whose cells were not producing any GAA.

All four children who received the immunosuppression regimen benefited from Myozyme treatment.

For more information, read:

Genzyme studying how to induce tolerance to Myozyme

Genzyme, the company that developed Myozyme and Lumizyme, is studying the best way to bring about immunologic tolerance to Myozyme.

For details and contact information on this small (nine-person) study, see Immune Tolerance Induction Study; or go to and enter NCT00701701 in the search box.

MDA grantee studying immune response to ERT

Eric Sjoberg at Amicus Therapeutics received an MDA grant in early 2012 to study the immune response some people have to ERT. Sjoberg and colleagues also will determine whether an experimental drug called AT2220, in development at Amicus, can dampen an ERT-related immune response.

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