|Drs Jae Young Lee and Steven Petratos, first and last authors |
respectively on the paper
Monash University researchers have developed – and patented – a small molecule that holds promise as a drug to help treat diseases affecting motor control, including Multiple Sclerosis (MS).
Led by Dr Steven Petratos, the researchers investigated the molecule, called DITPA, in a rare disorder called Allan-Herndon-Dudley syndrome (AHDS). The condition, which starts developing before birth, causes psychomotor retardation, whereby the person cannot control movement in their body and can have severe intellectual disability. It is inherited via a genetic mutation and only affects males.
The scientists were assessing a group of molecules affecting the development of mature human brain cells called oligodendrocytes, which play an important role in interacting with, supporting and protecting nerve fibres. Diseases such as MS or AHDS occur when the protective covering provided to the nerve fibres by the supporting brain cells is damaged or missing.
Their study, which used human embryonic stem cells, showed that people with AHDS had abnormal development of these brain cells.
“We serendipitously found that one small molecule has a very significant effect on these cells in terms of their development from an immature cell, a stem cell, to a mature cell in the brain,” Dr Petratos said.
“Our new finding is that altering a gene in these specific cells as they were developing caused them to die, effectively mimicking the disease process. DITPA - this small molecule or drug - was able to prevent the death of these cells, thereby allowing them to develop into mature cells with a normal physiological function,” he said.
The findings were published in the translational medicine journal EBioMedicine.
The drug could potentially be used therapeutically in utero or at an early age to improve the lives of patients with AHDS, Dr Petratos said. Moreover, the findings may apply to other diseases.
The researchers are now seeking funding from MS organisations for preclinical work investigating the drug in experimental forms of MS. If successful, clinical trials would follow in the future.
“The excitement is that we are now leading into that area so if our funding is successful it may be a big game-changer in giving options for MS patients in the future,” he said. “There’s considerable commercial interest in this.”
Although trials elsewhere have used the drug on humanitarian grounds to treat AHDS patients they have not been ongoing. Dr Petratos’ team is the first to take a different tack and demonstrate its effects on the development of human oligodendrocytes.
Dr Petratos, who leads a laboratory in the new Department of Neuroscience, Central Clinical School, was aided by PhD students Jae Young Lee, and Min Joung Kim, who were first co-authors on the paper. Dr Jae Young Lee recently won the Dean’s Award for Doctoral Thesis Excellence partly for his work on the study.
The research was supported in part by Multiple Sclerosis Research Australia, Trish MS Research Foundation, National Multiple Sclerosis Society (US) and NeuOrphan Pty Ltd.
Jae Young Lee, Min Joung Kim, Devy Deliyanti, Michael F. Azari, Fernando Rossello, Adam Costin, Georg Ramm, Edouard G. Stanley, Andrew G. Elefanty, Jennifer L. Wilkinson-Berka, Steven Petratos. Overcoming Monocarboxylate Transporter 8 (MCT8)-Deficiency to Promote Human Oligodendrocyte Differentiation and Myelination. EBioMedicine DOI: 10.1016/j.ebiom.2017.10.016