Stem cell therapies for brain disorders
Stem cell therapies, Alzheimer's, Multiple Sclerosis
2017 Red Lab Coat Day. L-R: Ms Erica Kim, Dr Steven Petratos, Mr Tom Bedford, Ms Amy Stone.
Of the approximate 2.5 million patients diagnosed and living with multiple sclerosis (MS) globally, the impact of MS regarding quality of life (QOL) and global health burden increases significantly once patients convert from relapsing remitting to Progressive MS and there exists a lack of tangible therapeutic options for the >50% of patients that progress even whilst on currently available FDA approved medications (12 available). Multiple sclerosis (MS) is commonly induced by the specific destruction of the protective sheath of nerve fibres, known as myelin, by immune cells, which mistakenly attack this structure. However, it has been shown that MS does not only consist of this disease pattern but is a multifactorial disease with continual destruction of the nerve fibres even without large numbers of immune cells invading the brain and the spinal cord. Importantly, the molecules which may contribute or initiate such damage in MS are becoming known and by targeting these molecules during MS it may be possible to limit the destruction which occurs to nerve fibres in the brain and spinal cord, promoting a better clinical outcome for individuals suffering with MS. We are investigating how damage occurs in nerve fibres with progressive clinical symptoms in the experimental animal model of MS and are targeting this mechanism to block the molecules that propagate the nerve fibre degeneration using novel stem cell-based strategies to deliver agents to the brain and spinal cord.
We have also initiated a drug development project for a repurposed drug with accelerated translation potential and path to market for Progressive Multiple Sclerosis, an unmet medical need. We are trialling a drug benchmarked against drugs of its class currently in clinical trials that may help promote the generation of new oligodendrocytes and myelin to promote neuroprotection and repair.
Alzheimer's disease (AD) is one of the most prevalent severe neurological disorders afflicting our aged population. Cognitive decline, a major symptom exhibited by AD patients, is associated with neuritic dystrophy, a degenerative growth state of neurites. The molecular mechanisms governing neuritic dystrophy remain unclear. Mounting evidence indicates that the AD-causative agent, β-amyloid protein (Aβ), induces neuritic dystrophy. Our group is investigating potential molecular pathways, which may be modulated subsequent to Aβ-dependent interactions with the neuronal membrane as a consequence of increasing amyloid burden in the brain.
Projects and Opportunities
None currently available.
See more publications at Dr Steven Petratos's profile
- Petratos S., Ozturk E, Azari MF, Kenny R, Lee JY, Magee KA, Harvey AR, McDonald C,
Taghian K, Moussa L, Aui PM, Siatskas C, Litwak S, Fehlings MG, Strittmatter SM, Bernard
CCA (2012) Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and
CRMP-2 phosphorylation. Brain 135, 1794-1818 .
- Lee JY and Petratos S. Multiple Sclerosis: Does NOGO Play a role? The Neuroscientist
- Alsanie W., Niclis J., Petratos S. (2013) Human ESC derived oligodendrocytes: Protocols
and perspectives. Stem Cells and Development 22(18):2459-76.
- Petratos S and Lee JY. (2013) Stop CRMPing my style: A new competitive model of CRMP
oligomerization. Journal of Neurochemistry 125(6):800-2.
- Mokhtar SH, Bakhuraysah MM, Cram DS, Petratos S. (2013) The Beta-amyloid protein of
Alzheimer's disease: communication breakdown by modifying the neuronal cytoskeleton.
International Journal of Alzheimers Disease. 2013:e910502.
- Litwak SA, Payne NL, Campanale N, Ozturk E, Lee JY, Petratos S, Siatskas C,
Bakhuraysah M, Bernard CC. Nogo-receptor 1 deficiency has no influence on immune cell
repertoire or function during experimental autoimmune encephalomyelitis. PLoS One. 2013
- Sutinen EM, Korolainen MA, Häyrinen J, Alafuzoff I, Petratos S, Salminen A, Soininen H,
Pirttilä T, Ojala JO. (2014) Interleukin-18 alters protein expressions of neurodegenerative
diseases-linked proteins in human SH-SY5Y neuron-like cells. Frontiers in Cellular
- Lee JY, Taghian K, Petratos S. (2014) Axonal degeneration in Multiple Sclerosis. Can we
predict and overcome a permanent disability? Acta Neuropathologica Communications.
- Alshehri B., D’Souza DG., Lee JY., Petratos S., Richardson SJ. (2015) The diversity of
mechanisms influenced by transthyretin in neurobiology: development, disease and
endocrine disruptors. Journal of Neuroendocrinology 27(5):303-323.
- Lee JY, Biemond M, Petratos S. (2015) Axonal degeneration in multiple sclerosis: defining
therapeutic targets by identifying the causes of pathology. Neurodegenerative Disease
- Bakhuraysah MM, Siatskas C, Petratos S. (2015) Is Hematopoietic Stem Cell
Transplantation for Multiple sclerosis a clinical reality? Stem Cell Research & Therapy 7
- Deliyanti D, Lee JY, Petratos S, Meyer C, Ward KW, Wilkinson-Berka JL, de Haan JB.
(2015) A potent Nrf2 activator, dh404, bolsters antioxidant capacity in glial cells and
attenuates vasculopathy in mice with ischaemic retinopathy. Clinical Science 130(15):1375-
- Dahl LCM, Nasa Z, Chung JY, Niego B, Tarlac V, Ho H, Galle A, Petratos S, Lee JY,
Alderuccio F, Medcalf RL (2016) The influence of differentially expressed tissue-type
plasminogen activator in experimental autoimmune encephalomyelitis: Implications for
multiple sclerosis. PLoS ONE 11(7):e0158653.
- Lee JY & Petratos S (2016) Thyroid hormone signaling in oligodendrocytes: From
extracellular transport to intracellular signal. Molecular Neurobiology 53(9):6568-6583.
- Tolcos M, Petratos S, Hirst JJ, Wong F, Spencer SJ, Azhan A, Emery B, Walker DW. (2017)
Blocked, Delayed, or Obstructed: What Causes Poor White Matter Development in Intrauterine Growth Restricted Infants? Progress in Neurobiology 154:62-77 (5Yr
- Lee JY, Li L, Velumian AA, Aui PM, Fehlings MG, McLean C, Petratos S. (2017) Nogo
receptor 1 regulates axo-glial units in the central nervous system. Scientific Reports 7:8598
- Lee JY, Kim MJ, Deliyanti D, Azari MF, Rossello F, Stanley EG, Elefanty AG, Wilkinson-Berka
JL, Petratos S. (2017) Overcoming monocarboxylate transporter 8 (MCT8)-deficiency to
promote human oligodendrocyte differentiation and myelination. EBioMedicine 25:122-135.
- National Phase (PCT/AU2015/000770; #WO2016/101017A1 in the name of NeuOrphan
Pty Ltd entitled: Improvements in oligodendroglial cell culturing
methods and in methods for treating neurodegenerative disorders
by using thyroid hormones or analogues).
Previous and Current funding
- National Multiple Sclerosis Society (USA) Project Grant
- National Multiple Sclerosis Society (USA) Project Grants
- International Progressive Multiple Sclerosis Alliance Challenge Award
- Multiple Sclerosis Research Australia Project Grants
- Trish Multiple Sclerosis Research Foundation Project grants
- Bethlehem Griffiths Research Foundation Project Grant
- NeuOrphan P/L Commercial Grant