Cross-correction in IEM. In the peripheral circulation (left panel), enzyme is delivered to the tissues either by diffusion of plasma enzyme (derived from pharmacologically delivered enzyme or from secretion by donor leukocytes) or by leukocytes leaving the circulation and entering the tissues. In the CNS (right panel), enzyme is delivered by the latter means only because the blood-brain barrier does not permit diffusion of the plasma-derived enzyme. Therefore, ERT does not correct CNS disease, but HSCT does.