The lower motor neurons in the spinal cord specifically deteriorate in SMA patients. Messages from the spinal cord can no longer be efficiently passed to their target muscles, which makes movement difficult. Muscles then waste or atrophy due to lack of use.
Neuroprotection aims to support motor neurons by restoring their function and/or preventing their death. Unlike approaches that target the SMN1 or SMN2 genes, this approach does not address the underlying genetics of SMA. However, it could be readily used in combination with therapies that do indeed attempt to restore SMNprotein levels, such as SMN1 gene therapy.
The main neuroprotective strategy currently being studied for SMA is based on looking for neuroprotective small molecules that help nerve cells to stay alive and functional.
Olesoxime is a small molecule drug first identified and developed by the French pharmaceutical company Trophos, and acquired by Roche in January 2015. It is the main neuroprotective chemical being tested as a potential treatment for SMA. Available in liquid form, enabling easy oral administration, Olesoxime has been shown to protect nerve cells from damage in cell culture, while improving neuronal growth and function. Results from a relatively large-scale Phase II study of Olesoxime were recently reported suggesting that the drug may be beneficial to SMA patients.