Genetically modified stem cells can survive in the spinal cords of ALS patients for at least three years. There they make a substance that protects dying nerve cells. This is apparent from a first trial with eighteen patients, who experienced no serious side effects. The experiment was still too small to determine whether the treatment slows down the course of the disease. American researchers published their findings this week in the medical science Nature Medicine.
In the progressive disease amyotrophic lateral sclerosis (ALS), the motor nerve cells that control the muscles are destroyed. This leaves patients increasingly paralyzed, from the legs to the respiratory muscles. There is no treatment; without a ventilator, the disease leads to death in an average of three years. Every year 400 to 500 people in the Netherlands hear that they have ALS.
The Americans made clever use of two well-known insights. ALS patients are also affected by astrocytes, the supporting cells that care for and repair nerves. In addition, it is known that the substance GDNF promotes the growth of motor nerve cells. But injecting that substance doesn’t work: it breaks down quickly and barely enters the brain and spinal cord.
Tackling nerve breakdown
The researchers therefore used human neuronal stem cells that can grow into astrocytes. They genetically modified it in such a way that they made the substance GDNF. They hoped to tackle the nerve breakdown in two ways.
They injected the stem cells into the spinal cords of 18 ALS patients, near the motor nerve cells that control the muscles of one of their legs. The other leg served as an untreated control.
After the transplantation, the stem cells grew into astrocytes in the spinal cord that made the protective GDNF for at least three years. None of the patients experienced serious side effects.
The Americans measured the muscle strength of the patients. The loss of strength in the treated legs was on average somewhat slower than in the untreated legs, and it was slower in people on a high dose than in people on a low dose. But the number of participants was still too small to determine whether the treatment actually slows down the breakdown of nerve cells.
It is one of the best experimental transplant studies, says molecular neurobiologist Jeroen Pasterkamp, who leads ALS research at UMC Utrecht. “Previous ALS studies worked with cells that become motor neurons. That doesn’t work because they don’t make new connections in the spinal cords of patients. I am more positive about this new approach, in which they transplant support cells that also make GDNF. That combination really seems to do something.”
There are two drugs for ALS, but they have little effect. Pasterkamp: “We need this. We need to build a portfolio of medications and treatments that can work for patients, and this contributes to that.”