Motor neurone disease gene therapy proven safe

A new combined stem cell and gene therapy that promotes the survival of motor neurons in patients with motor neurone disease has been deemed safe for use in humans.

The safety trial was carried out by researchers from the Cedars Sinai Medical Centre in Los Angeles, California and its findings published in the journal of Nature Medicine. This trial used a new stem cell technology to provide motor neurons with stem cells that produce survival promoting proteins via the spinal cord. One such protein, glial cell line-derived neurotrophic factor (GDNF), would otherwise not reach the motor neurons due to the blood-brain barrier, which protects the brain against any microorganisms that could be within the blood.

'Using stem cells is a powerful way to deliver important proteins to the brain or spinal cord that can't otherwise get through the blood-brain barrier,' said senior and corresponding author Professor Clive Svendsen. 'We were able to show that the engineered stem cell product can be safely transplanted in the human spinal cord. And after a one-time treatment, these cells can survive and produce an important protein for over three years that is known to protect motor neurons that die in ALS.'

Motor neurone disease, also known as amyotrophic lateral sclerosis (ALS), is a fatal neurodegenerative disorder which leads to the progressive loss of motor neurons that are needed for movement and breathing. Motor neurons are thought to die due to having less healthy support cells, known as astrocytes, around them. Moreover, less survival promoting proteins, such as GDNF, are available to keep the motor neurons alive.

The trial was run to determine the safety and efficacy of the new stem cell therapy using 18 patients diagnosed with motor neurone disease. After administration of the engineered stem cells via their spinal cords, the patients were given immunosuppressants for one year following the transplant to prevent their bodies rejecting the unfamiliar stem cells. The results showed that after 42 months, 13 patients showed GDNF production and no signs of transplant rejection, with the exception of one participant, despite halting the use of immunosuppressants after one year.

This is the first study to demonstrate that GDNF producing stem cells can be safely transplanted into the human spinal cord, where none of the 18 patients experienced any severe side effects. Moreover, this study showed that the stem cells can survive transplantation, become healthy astrocytes, and keep producing GDNF, years after transplantation.

'We're excited that we proved safety of this approach, but we need more patients to really evaluate efficacy, which is part of the next phase of the study,' said Dr J Patrick Johnson, co-medical director of the Spine Centre at Cedars-Sinai, and co-lead author. 'Proving that we have cells that can survive a long time and are safe in the patient is a key part in moving forward with this experimental treatment.'