Information pages published by

The Jennifer Trust for Spinal Muscular Atrophy

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Stem Cell Transplantation for Spinal Muscular Atrophy By Orest Hurko, MD from The Muscular Dystrophy Campaign, Cambridge, UK

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For over a century it has been known that individual cells taken out of the body can survive and develop into mature forms that have many of the attributes of nerve or muscle cells. Initially, scientists could only harvest limited numbers of cells that could only develop into those tissues from which they were isolated. More recently investigators discovered stem cells, which can divide in tissue culture to yield the enormous quantities needed for treatment and then mature into non-dividing cells with any of a number of capabilities. Although stem cells were thought to be present only in embryos, we now know that they are present in brain, bone marrow, and other tissues of adults. Other researchers have been able to insert genes into tissue cultured cells in order to increase cell division or to produce special chemicals, such as neurotransmitters or growth factors.

Some twenty years ago, physicians began injecting these cells back into experimental animals and into patients. It had long been known that mature bone marrow harvested from donors could be used to treat patients whose blood-forming marrow has been destroyed by chemotherapy. However, it was not known if donor cells could integrate into a complex structure such as the nervous system or muscle. Over a decade ago, experiments with Parkinson's disease and muscular dystrophy showed that they could.

However, these same experiments also brought to light a serious limitation. Injected cells can only penetrate solid tissues for one or two millimetres. Fortunately, in Parkinson's disease the basal ganglia sit right next to the fluid filled ventricle where the cells can be injected easily. In muscle tissue, the situation proved much more difficult. Even the smallest human muscle requires hundreds of injections spaced a few millimetres apart.

This seemed an insurmountable problem for spinal cord, where nerve cells would have to be transplanted for treatment of SMA or ALS. Injections every few millimetres would be impossible. A few months ago, preliminary findings showed that some of the stem cells injected into the large fluid filled cavities of a rat brain dropped down as far as the spinal cord. There, some of them crawled along the outside of penetrating vessels to enter the spinal cord itself.

This finding is certain to stimulate new research. However, many more pieces need to be fitted to the puzzle if this experiment is ever to be translated into a treatment for patients with motor neurone disease. In the rat experiment, only a tiny fraction of the injected cells found their way into the spinal cord. Furthermore, not all parts of the spinal cord got an even share. And the rat spinal cord is only a few millimetres thick, much smaller than a human. Equally importantly, we have yet to see if such cells will make all the necessary connections. For a motor neuron to work properly, it must extend a process up to a metre in length to attach itself to a muscle. Furthermore, it must make the necessary internal connections with controlling neurons from brain and limbs. Such connections must be made with great precision. A motor nueron controlling the thumb would be of limited value if it hooked up with a brain neuron controlling hip movement. It is crucial that transplanted neurons survive longer than the few weeks of the rat experiment. Finally, all the stem cells must stop dividing. Even a few renegade cells could potentially give rise to a tumour.

Although the final solution to these and many other potential problems as yet can only be imagined, these new findings give us hope that stem cell transplantation may some day improve the lives of patients suffering from the motor neuron diseases.