Selective lesions of rabbit extraocular muscles injected with the anti-AChR immunotoxin saporin-mAb 73

PURPOSE: To evaluate the effects on extraocular muscles of a skeletal muscle-specific immunotoxin, saporin-mAb 73, as an alternative to botulinum toxin to induce a permanent correction of oculo-facial dystonias or some forms of ocular motility disorders. METHODS: An immunotoxin was prepared with a monoclonal antibody (mAb 73) against acetylcholine receptors of skeletal muscle, linked to saporin, a type 1 ribosome-inactivating protein (RIP) from Saponaria officinalis. Sixteen New Zealand white rabbits were treated with a single injection of immunotoxin directly into the medial rectus muscle of one eye. Four different dosages of 2, 5, 20, or 50 ng saporin-mAb 73 were used. The rabbits were sacrificed at two, 7 and 14 days post-injection. The medial rectus muscle and the retractor bulbi muscle of both the injected and the fellow eyes were taken and serial sections were examined by light microscopy in a blinded manner. RESULTS: Saporin-mAb 73, even at the dosage of 2 ng, brought about focal damage in the extraocular muscles of rabbits without histological changes in adjacent muscles. The histological examination revealed necrotic/apoptotic lesions restricted to the sites of inoculation and largely infiltrated by macrophages. No evident inflammatory reaction was detected at any time and neutrophils were substantially absent. At 14 days after injection, necrosis/apoptosis was still evident and the sclerotic reaction was minimal. CONCLUSIONS: The immunotoxin saporin-mAb 73 injections into the extraocular muscles of rabbits caused focal damage to the muscles. There was no significant inflammatory reaction and muscle fiber loss was present even at the lower doses. Although the lesions were followed for only 14 days, our results suggest that saporin-mAb 73 has potential to cause safe focal muscle damage but longer-term follow-up are needed to investigate the persistence of muscle weakness.     

Recent advances in hormonal male contraception

Hormones inhibit fertility in men by suppressing sperm production. Testosterone-enanthate induced azoospermia has proven to provide optimal contraceptive protection. Preliminary studies have shown that testosterone alone or androgen-progestin combinations induce profound sperm suppression in the Eastern and white populations, respectively. Thus, these regimens may represent viable options for male contraception. New long-acting androgen formulations represent a major advancement in this field, allowing for the development of more acceptable and effective regimens.     

The neural basis of functional brain imaging signals

The haemodynamic responses to neural activity that underlie the blood-oxygen-level-dependent (BOLD) signal used in functional magnetic resonance imaging (fMRI) of the brain are often assumed to be driven by energy use, particularly in presynaptic terminals or glia. However, recent work has suggested that most brain energy is used to power postsynaptic currents and action potentials rather than presynaptic or glial activity and, furthermore, that haemodynamic responses are driven by neurotransmitter-related signalling and not directly by the local energy needs of the brain. A firm understanding of the BOLD response will require investigation to be focussed on the neural signalling mechanisms controlling blood flow rather than on the locus of energy use.