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 (Roche) is a small molecule drug first identified and developed by the French pharmaceutical company Trophos, and acquired by Roche in January 2015. It was 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.
In 2016 Roche started the OLEOS study, an open label extension study evaluating the long term safety and effectiveness of olesoxime. The data from the study has been regularly analysed. Whilst the data at 12 months of treatment with olesoxime were initially encouraging, the most recent analysis at 18 months, which was presented at the American Academy of Neurology in April 2018, actually showed a worsening in motor function. Roche has made the difficult decision of stopping the development of olesoxime. For more information, please read Roche’s community update (May 2018).