Funding for studies into tumors of the nervous system

November 26, 2012

A research team from Plymouth University Peninsula Schools of Medicine and Dentistry has received grants amounting to over £400,000 from the Medical Research Council and Cancer Research UK to investigate why the mechanisms that suppress the growth and multiplication of tumours in the brain and nervous system do not work in some people, and to show how an existing drug could be used as an alternative treatment to surgery.

The Medical Research Council study will last for three years and the Cancer Research UK study for one. They are the latest in a succession of studies carried out by the medical school research teams into the biology of tumours in the nervous system.

Tumour suppressors exist in cells to prevent abnormal cell division in our bodies. The loss of a tumour suppressor called Merlin leads to tumours in many cell types within our nervous systems. There are two copies of a tumour suppressor, one on each chromosome that we inherit from our parents. The loss of Merlin can be caused by random loss of both copies in a single cell, causing sporadic tumours, or by inheriting one abnormal copy and losing the second copy throughout our lifetime as is seen in the inherited condition of neurofibromatosis type 2 (NF2).

With either sporadic loss or inherited NF2, these tumours lacking the Merlin protein develop in the Schwann cells that form the sheaths that surround and electrically insulate neurons. These tumours are called schwannomas, but tumours can also arise in the cells that form the membrane around the brain and spinal cord, and the cells that line the ventricles of the brain.

Although the tumours are slow-growing and benign, they are frequent and come in numbers. The sheer number of them can overwhelm a patient, often leading to hearing loss and eventually death. Patients can suffer from 20 to 30 tumours at any one time, and the condition typically manifests in the teenage years and through into adulthood.

No effective therapy for these tumours exists, other than repeated invasive surgery aiming at a single tumour at a time and which is unlikely to eradicate the full extent of the tumours.

NF2 affects one in every 25,000 people worldwide It can affect any family, regardless of past history, through gene mutation and currently there is no cure.

The Medical Research Council-funded research project will investigate how loss of a protein called Sox10 functions in causing these tumours. Sox10 is known to play a major role in the development of Schwann cells, but this is the first time it has been shown to be involved in the growth of schwannoma tumour cells. By understanding the mechanism, it is hoped that therapies can be developed that will provide a viable to alternative to surgery.

The Cancer Research UK-funded project is in collaboration with researchers at the Memorial Sloan-Kettering Institute in New York. It aims to show that an existing drug, MLN4924, could be used to slow or even reverse the progression of tumours in the brain and nervous system. Once the research team has achieved validation for the drug they will then take it forward to clinical trials. By investigating an existing drug in this way it is possible to develop comparatively rapidly potential therapies for patients.

The Medical Research Council-funded project is led by David Parkinson, Professor in Neuroscience at Plymouth University Peninsula Schools of Medicine and Dentistry, in collaboration with his colleague Professor Oliver Hanemann. He said: "Patients who suffer from multiple tumours in the brain and nervous system face a lifetime of surgery and debilitation. By understanding how Sox10 works we can lay the groundwork for the development of potential therapies that could remove the need for surgery and improve the lives of people around the globe who are affected by these tumours. We are very grateful to the Medical Research Council and Cancer Research UK for their support."

Professor Oliver Hanemann, who leads the Cancer Research UK-funded project, added: "Both studies aim to find and put into practice viable, safe and effective drug-based treatments for patients with NF2 - patients for whom at present there is no alternative treatment to repeated surgery. By investigating our body's own mechanisms and understanding how they work, and by researching the potential of existing drugs, we hope to achieve safe and effective treatments for NF2 sufferers in a relatively quick and timely manner."

The Peninsula College of Medicine and Dentistry

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