With funding from the California Institute for Regenerative Medicine (CIRM), Cedars-Sinai scientists are testing a gene and cell therapy to treat amyotrophic lateral sclerosis (ALS), a fatal neurological disorder known asLou Gehrig’s disease.
In the first trial of its kind, the Cedars-Sinai team showed that delivery of this combined treatment is safe in humans. The findings were reported in the peer-reviewed journal Nature Medicine.
What causes ALS?
ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. About 6,000 people are diagnosed with ALS each year in the U.S., and the average survival time is two to five years.
The disease occurs when the cells in the brain or spinal cord that tell muscles to move—called motor neurons—die. People with the disease lose the ability to move their muscles and, over time, the muscles atrophy and people become paralyzed and eventually die. No effective therapy exists for the disease.
Using Stem Cells to Treat ALS
In a news release, senior author Clive Svendsen, PhD, executive director of the Cedars‑Sinai Board of Governors Regenerative Medicine Institute, said stem cells show strong promise for treating ALS.
“We showed the engineered stem cell product can be safely transplanted into the human spinal cord. After a one‑time treatment, these cells can survive and produce a protective protein for more than three years,” Svendsen said.
The goal is to preserve leg function in patients with ALS. The engineered cells could offer a new therapeutic option for a disease that causes progressive paralysis and robs people of movement, speech, and breathing.
The study used stem cells engineered in Svendsen’s lab to produce GDNF, a protein that supports motor neurons. In ALS, diseased glial cells lose their ability to support these neurons. As a result, motor neurons degenerate and paralysis develops.
By transplanting GDNF‑producing stem cells into the spinal cord—where compromised motor neurons reside—the cells can become supportive glial cells and release GDNF, helping motor neurons survive.
Ensuring Safety in the Trial
The trial’s primary goal was to confirm that delivering GDNF‑releasing cells to the spinal cord was safe and did not harm leg function. None of the 18 treated patients experienced serious side effects.
Because ALS patients typically lose strength in both legs at similar rates, investigators transplanted cells into only one side of the spinal cord. This allowed direct comparison of the treated leg to the untreated leg over the following year. The team found no negative effect on muscle strength in the treated leg.
What’s Next?
Researchers expect to start a new study soon with more patients. They will target a lower region of the spinal cord and enroll people earlier in the disease to increase the chance of seeing meaningful effects.
“We are very grateful to all the participants,” said Svendsen. “ALS is a very tough disease to treat, and this research gives us hope.”
Cedars‑Sinai is also testing GDNF‑secreting stem cells in another CIRM‑funded ALS trial, targeting the motor cortex—the brain region that controls hand movement.
CIRM remains committed to funding ALS research and clinical trials. To date, the agency has provided $93 million for ALS research.
Gene therapy is the treatment of any disorder or pathophysiologic state based upon the transfer of genetic information. The introducing of foreign gene into the cell induces overstimulation of the intracellular control processes which constitute a strong transforming signal. This appears to be the case is evidenced by oncogenic potential of the EGF(erbB), M-CSF(fms) and SLF(kit) receptors, each of which has been adopted as the basis of a viral oncogene. Hence, patients undergoing gene therapy have higher risk to develop cancers and it is the matter of time for tranducted cells to transform into cancers. Gene therapy is highly recommended to patients with high fatality rate of diseases, as there is no conventional medicine available to cure the diseases.
Current clinical investigation with both stem cells therapy cum gene therapy by using human neural progenitor cells transduced GDNF (CNS10-NPC-GDNF) which can be differentiated into astrocytes to protect spinal motor neurons. The results showed that most patients took almost long (1 year) to develop muscle strength. As mentioned earlier, stem cells require growth factors for growth and differentiation. The maturation of stem cells require many stages of development to become mature and functioning cells. Each stage of maturation, the cell requires specific growth factor for progenitor to switch on the gene and differentiate into more mature state of cell. Gene therapy with the only GDNF may ineffective or produce partially developed astrocytes. The immature astrocytes are not fully functioning with short lifespans do not translated clinical beneficial to ALS patients. Growth factors research plays key roles to determine specific growth factors for stem cells to develop into mature and functioning cells.