Transforming growth factor-beta 2 causes an acute improvement in the motor performance of transgenic ALS mice

Amyotrophic lateral sclerosis (ALS) is fatal disorder, characterized by the loss of motoneurons. The therapeutic potential of transforming growth factor-beta 2 (TGF-beta2) was examined using SOD1 mice. The SOD1 mice were treated with TGF-beta2 by repeated intraperitoneal injections. The highest dose of TGF-beta2 caused a rapid and marked improvement in the motor performance of the mice. This improvement lasted for between 2 and 3 weeks after which the TGF-beta2-treated mice rapidly deteriorated. At postmortem, the motoneurons in the TGF-beta2-treated SOD1 mice exhibited a large hypertrophy of their nucleoli, nuclei, and axons. In contrast, TGF-beta2 did not reverse the mitochondrial pathology. This may explain why the beneficial effects of TGF-beta2 and other growth factor on SOD1 mice are transient: TGF-beta2 is stimulating the motoneurons metabolic rate while one of their key metabolic organelles is damaged. Consequently, TGF-beta2 may be therapeutic for the forms ALS, with minimal mitochondrial involvement.