Will stem cells eventually outperform pharmaceuticals or will they come to Big Pharma’s rescue?

Author: Angela C. H. McDonald, 09/11/12

You don’t have to follow pharmaceutical industry news to know that this summer has been a disappointing one for Alzheimer’s research. Many major media outlets covered the failure of potential Alzheimer’s drug bapineuzumab (Pfizer/Johnson & Johnson) in Phase II/III clinical trials, announced earlier this summer. Another disappointment came late last month with the report of solanezumab’s (Eli Lilly) failure in a Phase II clinical trial.

Both drugs were designed to prevent beta-amyloid deposition in a patient’s brain (which is thought to be responsible for plaque formation and subsequent destruction of neurons leading to Alzheimer’s disease). However, both drugs failed to improve cognitive function in Alzheimer’s patients.

As someone who has watched a loved one deteriorate from Alzheimer’s disease, this left me pretty disheartened. But as a stem cell researcher, this news left me asking what can stem cells do for Alzheimer’s research?

Unlike the pharmaceutical industry, stem cell research has had an exciting summer when it comes to advances in Alzheimer’s research.

In July, StemCells, Inc. announced preclinical data describing the restoration of memory and enhanced neuronal communication by human neural stem cell transplantation in two animal models similar to Alzheimer’s disease.  StemCells, Inc.’s proprietary human neural stem cells were transplanted into the hippocampus region of the brain.  In Alzheimer’s patients, density of synapses (the part of a neuron that allows communication to other neurons) is reduced in the hippocampus. In StemCells, Inc.’s study, experimental mice had an increase in synaptic density and improved memory.

Intriguingly, researchers found that the improvement in cognitive function following human neural stem cell transplantation was independent of a reduction in beta amyloid levels (the target of recently failed pharmaceuticals).  Perhaps understanding what the transplanted neural stem cells are doing in these mice to improve cognitive function will uncover a novel pathology of Alzheimer’s disease and provide new therapeutic targets.

Also this summer, Stem Cell Network researcher Freda Miller published a report in Cell Stem Cell describing the ability of the diabetes drug metformin to promote the production of neurons from human embryonic stem cells, which could one day be used to create an alternative pool of cells for transplantation.

However, the most exciting finding reported in Miller’s study was the ability of metformin to promote the generation of new neurons in the adult mouse central nervous system, including the hippocampus (an area of the brain affected by Alzheimer’s disease). In behavioural studies, metformin-induced increases in hippocampal neuron production enhanced cognitive function suggesting that metformin could be a potential pharmacological candidate for the treatment of degenerative nervous system diseases such as Alzheimer’s. This is not the first study to suggest an association between an improvement in Alzheimer’s brain abnormalities and diabetes drugs.

While cell transplantation strategies to treat Alzheimer’s disease such as StemCells, Inc.’s may show promising results in preclinical research, this type of strategy is incredibly complicated. Despite this, Miller’s work on metformin suggests that screening small molecules for the ability to activate neuronal production within the body by activating endogenous stem cells is a worthwhile alternative.

But in the short term, as I have suggested before, stem cells could be used to generate screening tools for pharmaceutical companies allowing them to test the efficacy of their drugs on human neurons before spending hundreds of millions of dollars on failed clinical trials.

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Angela C. H. McDonald

Angela C. H. McDonald

PhD candidate at Hospital for Sick Children
Angela is a PhD student in the Stem Cell and Developmental Biology program at the Hospital for Sick Children in Toronto. She is currently utilizing pluripotent stem cells to understand the genetic regulation of endoderm development. As an avid supporter of public science education, she co-founded the high school outreach initiative StemCellTalks sits on numerous public education committees including the International Society for Stem Cell Research Public Education Committee and the Stem Cell Network Public Outreach Committee.
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