Highlighted recent publications

scientific data1) Using human stem cells to treat retinal disease

2) Motor neurons derived from the skin cells of a motor neurone disease patient

3) Clinical trial of mesenchymal stem cells in multiple sclerosis patients

4) Modelling Parkinson's disease using patient stem cell-derived neurons

5) Strategies to study myelination "in a dish"

6) Social understanding impairment in motor neurone disease patients

7) Building personalised synthesised voices for individuals with speech difficulties

1) Using human induced pluripotent stem cells to treat retinal disease.

Borooah S, Phillips MJ, Bilican B, Wright AF, Wilmut I, Chandran S, Gamm D, Dhillon B.

Prog Retin Eye Res. 2013 Oct 5. pii: S1350-9462(13)00058-X.

Degenerative diseases of the retina are amongst the commonest causes of blindness worldwide.  Currently there are few treatments to treat these diseases. Recent breakthroughs in biological science mean that it is now possible to create stem cells from a patient's cells.  This is important because stem cells offer a potentially inexhaustible source of human patient material for both research and, potentially, for future patient therapy. In this paper, Rowling Scholar Shyamanga Borooah and colleagues highlight the pathways for the development of these new therapies both for prevention prior to retinal degeneration as well as for cell replacement after degeneration has started.

2) Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability.

Bilican B, Serio A, Barmada SJ, Nishimura AL, Sullivan GJ, Carrasco M, Phatnani HP, Puddifoot CA, Story D, Fletcher J, Park IH, Friedman BA, Daley GQ, Wyllie DJ, Hardingham GE, Wilmut I, Finkbeiner S, Maniatis T, Shaw CE, Chandran S.
Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5803-8. Epub 2012 Mar 26.

This paper describes the findings of an international research team, led by Anne Rowling Clinic Co-Director Siddharthan Chandran, in partnership with investigators at King's College London, Colombia University, New York and the University of San Francisco.

The team generated motor neurons "in a dish", using skin cells from a patient with an inherited form of MND. The study discovered that abnormalities of a protein called TDP-43, implicated in more than 90 per cent of cases of MND, resulted in the death of motor neurons. This is the first time that scientists have been able to see the direct effect of abnormal TDP-43 on human motor neurons.

Using patient stem cells to model MND in a dish offers untold possibilities for how we study the cause of this terrible disease as well as accelerating drug discovery by providing a cost-effective way to test many thousands of potential treatments.

Prof Siddharthan Chandran, Anne Rowling Clinic Co-Director

3) Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study.

Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, Du MQ, Luan SL, Altmann DR, Thompson AJ, Compston A, Scott MA, Miller DH, Chandran S.

Lancet Neurol. 2012 Feb;11(2):150-6. doi: 10.1016/S1474-4422(11)70305-2. Epub 2012 Jan 10.

Prof Siddharthan Chandran led a clinical trial in which mesenchymal stem cells were administered to ten patients with secondary progressive multiple sclerosis invloving the visual pathways. This was primarily a feasibility and safety trial: no adverse events were noted. Secondarily, the team measured efficacy: there were improvements in visual acuity, evoked response latency and the area of the optic nerve. These encouraging results suggest that the mesenchymal cells conferred neuroprotection.

4) Parkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus.

Devine MJ, Ryten M, Vodicka P, Thomson AJ, Burdon T, Houlden H, Cavaleri F, Nagano M, Drummond NJ, Taanman JW, Schapira AH, Gwinn K, Hardy J, Lewis PA, Kunath T.

Nat Commun. 2011 Aug 23;2:440. doi: 10.1038/ncomms1453.

A genetic mutation that causes triplication of the α-synuclein gene causes an aggressive form of Parkinson's disease with dementia. Tilo Kunath and colleagues have derived induced pluripotent stem  (iPS) cells from a patient with this mutation, and differentiated them into midbrain dopaminergic neurons - the subtype that is most affected in Parkinson's disease. The neurons produce twice the amount of α-synuclein protein as those from an unaffected individual. These neurons will be useful to determine the mechanisms of neurodegeneration caused by excess α-synuclein and to test compounds that reduce α-synuclein levels.

5) In vitro modeling of central nervous system myelination and remyelination.

Jarjour AA, Zhang H, Bauer N, Ffrench-Constant C, Williams A.

Glia. 2012 Jan;60(1):1-12. doi: 10.1002/glia.21231. Epub 2011 Aug 19.

Anna Williams, Charles ffrench-Constant and colleagues have reviewed the current techniques available to investigate the mechanisms of myelination and remyelination in culture systems. They discuss the difficulty and importance of quantification of myelination and in particular remyelination, and provide predictions of how these techniques will and should develop in the future.

6) Evidence of social understanding impairment in patients with amyotrophic lateral sclerosis.

Cavallo M, Adenzato M, Macpherson SE, Karwig G, Enrici I, Abrahams S.

PLoS One. 2011;6(10):e25948. Epub 2011 Oct 5.

Theory of Mind is the ability to comprehend social intentions. Up to 50% of motor neurone disease patients have a frontal syndrome similar to frontotemporal dementia, which is characterised by Theory of Mind deficits. Sharon Abrahams and colleagues measured the performance of 15 motor neurone disease patients on social vs. non-social intentions. Here, they report a specific and selective deficit in the patients on social tasks only. The results support a continuum of cognitive dysfunction from frontotemporal dementia to motor neurone disease.

7) Building personalised synthesised voices for individuals with dysarthria using the HTS toolkit

Creer S, Green P, Cunningham S, Yamagishi J.

In "Computer Synthesized Speech Technologies: Tools for Aiding Impairment", John W. Mullennix and Steven E. Stern (Eds), IGI Global press, 2010.

When the speech of an individual becomes unintelligible due to a neurological disorder, a synthesised voice can replace that of the individual. The voice must be intelligible, natural-sounding and retain the vocal identity of the speaker. In this book chapter, Junichi Yamagishi and co-workers at the Edinburgh Centre for Speech Technology Research describe their work using Hidden Markov models to build personalised synthetic voices for two individuals with dysarthria.

For more information please email info@smart-mnd.org