Cedars-Sinai Investigators Confirm Safety of Therapy Targeting Motor Neurons That Die in Patients With ALS

For the first time, an investigational therapy using stem cells and a protective protein has been shown to be safe in humans. The therapy targets motor neurons that die in patients with ALS. The treatment, which investigators developed at Cedars-Sinai, could potentially protect diseased motor neurons in the spinal cord of patients with amyotrophic lateral sclerosis (ALS), a fatal neurological disorder known as Lou Gehrig’s disease. In the trial, which was conducted using human cells in a lab dish and then again in a small group of patients with ALS, no serious side effects were observed. This is an important step forward in developing a potential new treatment for this devastating disease. The findings were published in the peer-reviewed journal Nature Medicine.

“We’re excited that we proved the safety of this approach, but we need more patients to really evaluate efficacy, which is part of the next phase of the study,” said Johnson, who is also the vice chair of Neurosurgery at Cedars-Sinai. “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.” ―From Cedars-Sinai

Pablo Avalos, MD, Robert Baloh, MD, Ph.D., previously a professor of Neurology at Cedars-Sinai and now global head of neuroscience at Novartis, and J. Patrick Johnson, MD, co-medical director of the Spine Center at Cedars-Sinai, are co-lead authors on the publication.

“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 Clive Svendsen, PhD, professor of Biomedical Sciences and Medicine and executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute. “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.” ―From Cedars-Sinai

The engineered cells could be a powerful therapeutic option for those suffering from the disease that robs people of their ability to move and breathe.

The study used stem cells that were designed in Svendsen’s laboratory to produce a protein called glial cell line-derived neurotrophic factor (GDNF). This protein can help protect motor neurons, cells that send signals from the brain or spinal cord to a muscle so it can move.

“GDNF on its own can’t get through the blood-brain barrier, so transplanting stem cells releasing GDNF is a new method to help get the protein to where it needs to go to help protect the motor neurons,” said Pablo Avalos, MD, co-lead author on the paper and associate director of Translational Medicine in the Cedars-Sinai Board of Governors Regenerative Medicine Institute. “Because they are engineered to release GDNF, we get a ‘double whammy’ approach where both the new cells and the protein could help dying motor neurons survive better in this disease.” ―From Cedars-Sinai