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9 April, 2018 - 11:13 By Tony Quested

Cambridge breakthrough in brain regeneration

Cambridge University scientists may have found a way to improve the repair of brain injury or disease without the need for surgery.

A team at the Wellcome Trust/Cancer Research UK Gurdon Institute have identified a new type of stem cell in the brain which they say has a high potential for repair – a major goal of regenerative research. The breakthrough holds significant implications in instances of Alzheimer’s disease or head trauma, disease or ageing.

The brain is poor at repairing itself but the Gurdon team solution is to target stem cells ‘sleeping’ in patients’ brains.

Stem cells have the unique capacity to produce all the cells in the brain but are normally kept inactive in a form of cellular ‘sleep’ known as quiescence. Quiescent cells do not proliferate or generate new cells so any regenerative therapy targeting stem cells must first awaken them from this state.

In a study published in the journal Science, Dr Leo Otsuki and Professor Andrea Brand report the discovery in the brain of a new type of quiescent stem cell – known as ‘G2 quiescent stem cell’ – with higher regenerative potential than peer cells identified previously.

Importantly, G2 quiescent stem cells awaken to make the key types of cell in the brain (neurons and glia) much faster than known quiescent stem cells – making them attractive targets for therapeutic design.

Professor Brand said: “The brain is not good at repairing itself but these newly-discovered stem cells suggest there may be a way to improve its ability. These stem cells are in a dormant state but once awake have the ability to generate key brain cells.”

By studying the fruit fly (Drosophila), the authors identified a gene known as tribbles that selectively regulates G2 quiescent stem cells. The DNA of fruit flies has many similarities with that of humans, making them a useful model to understand human biology. Sixty per cent of human genes associated with disease are also found in Drosophila.

The tribbles gene has counterparts in the mammalian genome that are expressed in stem cells in the brain. The researchers believe that drugs that target tribbles might be one route to awakening G2 quiescent stem cells.

“We’ve found the gene that directs these cells to become quiescent,” adds Dr Otsuki. “The next step is to identify potential drug-like molecules that block this gene and awaken a person’s stem cells. We believe there may be similar quiescent stem cells in other organs and this discovery could help improve or develop new regenerative medicines.”

The study was paid for by the Royal Society and Wellcome Trust and core funding to the Gurdon Institute from the Wellcome Trust and Cancer Research UK.

The Gurdon Institute has a potent record in groundbreaking research – and in spinning out exciting life science enterprises.

More than 240 scientists work in the Gurdon Institute’s purpose-built laboratories on projects ranging from breast cancer and brain development to liver regeneration and leukaemia.  Many have made pioneering contributions to the fields of basic cell biology, cellular reprogramming, epigenetics and DNA repair.

Research conducted at the institute has already led to nine spin-out companies including KuDOS Pharmaceuticals, Abcam, Chroma Therapeutics, CellCentric, Mission Therapeutics and Talisman Therapeutics plus five candidate drugs. One of these, olaparib (Lynparza), has been approved in the UK, Europe and the US for use against ovarian cancers.

• PHOTOGRAPH SHOWS: Professor Andrea Brand

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