An orally active anti-apoptotic molecule (CGP 3466B) preserves mitochondria and enhances survival in an animal model of motoneuron disease

1 Apoptosis and mitochondrial dysfunction are thought to be involved in the aetiology of neurodegenerative diseases. We have tested an orally active a nti-apoptotic molecule (CGP 3466B) that binds to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in an animal model with motoneuron degeneration, i.e . a mouse mutant with progressive motor neuronopathy (pmn). 2 In pmn/pmn mice, CGP 3466B was administered orally (10-100 nmol kg(-1)) a t the onset of the clinical symptoms (2 weeks after birth). CGP 3466B slowe d disease progression as determined by a 57% increase in life-span, preserv ation of body weight and motor performance. 3 This improvement was accompanied by a decreased loss of motoneurons and m otoneuron fibres as well as an increase in retrograde transport. Electron m icroscopic analysis showed that CGP 3466B protects mitochondria which appea r to be selectively disrupted in the motoneurons of pmn/pmn mice. 4 The data support evaluation of CGP 3466B as a potential treatment for mot or neuron disease.