Stem Cell-based Cell Therapy for Neurodegenerative Diseases

Had the good luck to attend the 9th Foundation Day of the National Brain Research Centre this Sunday evening. The guest speaker was Dr Mahendra S Rao, Director of Centre for Regenerative Medicine, NIH since 2011. He received his MD from Bombay University, followed by a PhD in developmental neurobiology from California Institute of Technology. He has also served at University of Utah, National Institute of Aging and Life Technologies. He is the co-founder of Q-therapeutics, a stem-cell research firm. His talk focussed on the application of stem cells to the study of neurodegenerative diseases. This post is a brief summary of his words.

Dr Mahendra S Rao, Director of Centre for Regenerative Medicine, NIH, US, responding to doubts on his talk – Stem Cells and Regenerative Medicine – on the 9th Foundation Day of National Brain Research Centre, India

Neurodegenerative Diseases
Human neurological disorders like Parkinson’s, Huntington’s, amyotrophic lateral sclerosis, Alzheimer’s, stroke, and spinal cord injury are caused due to loss of neurons and glial cells in the brain or spinal cord. Parallels between all these diseases include atypical protein assemblies as well as induced cell death. These similarities at the sub-cellular level hint that an effective therapeutic approach may treat many diseases simultaneously. Neurodegeneration may occur at many different levels of neuronal circuitry ranging from molecular to systemic. These diseases are thought to be closely linked with aging as most of them are late-onset.

Stem Cell-based Cell Therapy
There was evidence that new neurons are continuosly being generated in adult human CNS (Erkisson et al., 1988). But, capacity for repairs is very limited in adult CNS of patients suffering from neurodegenerative patients. It seems that the endogenous brain environment is responsible for induction of NSC proliferation and consequent NSC differentiation into neurons isn’t adequate.
The discovery of induced pluripotent cells (Takahashi and Yamanaka, 2006) accelerated stem cell research. The discovery wasn’t pluripotency – it was long speculated – but the combination of transcription factors required to induce pluripotency. On one hand, it overcame the ethical concerns and the federal restrictions on using embryonic stem cells while on the other it raised hopes for personalized medicine as the physicians could prepare iPS cells from the patient’s vey own somatic cells. As several diseases affecting central nervous system (CNS) are found to be related to cell-autonomous interactions, therapeutic strategies using stem cells are being seen as a lucrative approach to treat neurological disorders. In recent years, neurons and glial cells have been generated from stem cells like ESCs, MSCs, and NSCs. The three papers cited at the end (two of which are penned by Dr Rao himself) review almost all the progress in applying stem cells to treat neurological disorders.

Funding Translational Work
Regenerative medicine may well translate to revolutionary medicine. The revolution would be evident at every stage from drug development to patient response. The US FDA approved first clinical trial involving human ESCs on January 23, 2009. Geron Corporation, a biotech firm in California, enrolled 10 patients suffering from spinal cord injuries to participate in the trials. The company hoped that their product, GRNOPC1 (ESCs-derived oligodendrocyte progenitor cells) would stimulate nerve cell growth in the patients. The trial was discontinued in November 2011 due to financial instability of the firm.

Challenges that need to be tackled before stem cells can be brought from labs to clinics include –

  1. Cell manufacture issues : Neurons can be derived not only from NSCs but also from ESCs, EGCs, MSCs, umbilical cord hematopoietic stem cells and even iPSCs. Which cells are the best for treating neurodegenerative diseases? Also, ESCs remain the most viable and plastic stem cells yet. How can iPSCs achieve efficiencies at par with the iPSCs?
  2. Consent to obtain samples
  3. Designing an appropriate business model : The established drug development and sales models don’t suit the many aspects of cell therapy. The pioneers to come up with alternative commercialisation routes – to ensure that positive results become widely available and freely accessible – will be the next big entrepreneurs.

Read Further Here

  1. Rao, M., Stem cells and regenerative medicine, Stem Cell Research & Therapy, 2012, 3:27
  2. Kim, S U., Vellis, J de., Stem cell-based cell therapy in neurological diseases: A review, 2009
  3. Rao, M., Funding Translational Work in Cell-Based Therapy, Cell Stem Cell, July 8th, 2011

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