Figure 2.

Combination Therapies Normalize Biochemical Features of Murine Krabbe Disease

(A) GALC activity is deficient in untreated Twi brains (Twi Untr). Compared to untreated WT mice (WT Untr), Twi mice treated with AAV2/9-GALC alone (Twi AAV2/9), 2xRx therapy (Twi 2xRx), and 3xRx therapy (Twi 3xRx) have at least physiologic levels of GALC activity in the brain. Psychosine levels in (B) brain and (C) sciatic nerve are much higher in Twi Untr mice compared to WT Untr mice and Twi mice treated with AAV2/9-GALC alone, 2xRx therapy, or 3xRx therapy. All therapies significantly decrease psychosine accumulation in brain and sciatic nerves throughout the lives of Twi mice. (D) There is no significant difference in donor (GFP⁺) bone-marrow engraftment between Twi or WT mice receiving 2xRx or 3xRx therapies. The error bars represent one standard error of the mean, *p < 0.05, **p < 0.01.