GTC Biotherapeutics (fka GTCB)

[dewophile]

AAT deficiency
I found this article very informative:

http://www.emedicine.com/med/topic108.htm

this is the section on AAT replacement:

Replacing enzymes

AAT-deficient individuals who have or show signs of developing significant emphysema can be treated with Prolastin, a pooled, purified, human plasma protein concentrate replacement for the missing enzyme that has been screened for HIV and hepatitis viruses although practitioners should immunize patients against hepatitis regardless. It also is heat-treated as an additional precaution against transmission of infection The US Food and Drug Administration (FDA) has approved 2 other AAT protein concentrates, Aralast and Zemaira, for augmentation therapy.

Weekly IV infusions of AAT protein concentrates restore serum and alveolar AAT concentrations to protective levels. Although other dosing regimens have been used, only the weekly infusion schedule has US FDA approval.

No controlled studies have proven that IV augmentation therapy improves survival or slows the rate of emphysema progression. Results from the NIH patient registry and a comparison of Danish and German registries have been published, and both suggest that augmentation therapy has beneficial effects. Although they were not controlled treatment trials, the similarity of the results suggests that the findings are significant.

The NIH report described an overall death rate 1.5 times higher for those who did not receive augmentation therapy and a rate of FEV1 decline (54 mL/y) in AAT-deficient individuals about twice that of healthy nonsmokers but about 50% that of smokers (108 mL/y). Prolastin augmentation therapy did not improve the average FEV1 decline (54 mL/y); however, participants with moderate airflow obstruction (FEV1 35-60% of predicted value) had a slower rate of decline (mean difference 27 mL/y). These findings bolster the long-held belief that augmentation therapy provides clinical benefit. Studies of Aralast and Zemaira have shown equivalency with Prolastin in achieving and maintaining AAT serum levels and alveolar epithelial levels above the target level. No studies of Aralast or Zemaira have been done to show affects on FEV1, rate of decline of FEV1, or survival.

While no firm guidelines have been developed for initiating or continuing augmentation therapy, most pulmonary physicians require the serum level to be below the threshold protective value and that the patient have 1 or more of the following: signs of significant lung disease: chronic productive cough or unusual frequency of lower respiratory infection, airflow obstruction, accelerated decline of FEV1, or chest radiographic or CT evidence of emphysema.

The ATS recommends starting treatment when the FEV1 is <80% of the patient's predicted value, though the benefits of augmentation therapy for individuals with severe (FEV1 < 35%) or mild (FEV1 > 60%) airflow obstruction are less, as shown in studies with Prolastin.

Evidence for the use of AAT augmentation in patients after lung transplantation for AAT deficiency is insufficient. However, observational studies do show that inflammation from acute rejection or infection allows for free elastase activity in the epithelial lining fluid of individuals who have undergone lung transplantation. Therefore, the ATS/ERS Task Force favors the use of augmentation therapy for lung transplant recipients during episodes that provoke inflammation.