What is PEG-ADA enzyme replacement?

One particular kind of SCID, called adenosine deaminase deficiency (ADA)-SCID, is caused by lack of an enzyme (a protein in the body that helps break down other chemicals). Patients with ADA-SCID typically have very low T-cells, B-cells, and NK-cells because toxic byproducts build up as result of lack of the ADA enzyme. Patients with ADA-SCID present with similar infections as seen with the other forms of SCID.

ADA-SCID is the only type of SCID where patients can receive enzyme replacement. The enzyme has been made into a drug known as PEG-ADA (Adagen ®). At the present time, PEG-ADA comes from cows (bovine), although attempts are underway to make a recombinant form that does not come from animals. PEG-ADA is given by a needle into the muscle (intramuscularly). Patients / parents learn to inject it themselves. Usually it is given once per week, although dose changes (both in terms of total dose and the frequency with which PEG-ADA is administered) may need to occur based upon ADA levels that are monitored in the blood.

Patients with ADA-SCID can take PEG-ADA for their entire lifetime. In some situations it is used as a “bridge” to transplant (i.e. used to improve the immune system temporarily while a patient is awaiting more definitive therapy). It is controversial which approach is better. One of the goals of the PIDTC 6901 and 6902 studies is to understand long-term outcomes for both PEG-ADA and transplant for ADA-SCID.

Patients taking PEG-ADA may experience reactions to the medication. In some situations, patients will develop antibodies to the ADA enzyme, making it not work anymore. Some patients find that when they are younger the medication works well, but as they get older, it is less effective and the immune system is not functioning as well. One of the major disadvantages to PEG-ADA is that it is very expensive (sometimes in the hundreds of thousands of dollars per year).