Stem Cell Trial for ALS Patients

Two patients afflicted with amyotrophic lateral sclerosis have received stem cell injections into their spinal cords at the University of Michigan Health System. These are the first two subjects in a national clinical trial.

Both of these volunteers have returned home and will continue to receive medical follow-up and monitoring in order to assess the safety of this procedure and to detect any potential improvements in the condition of these patients.

Additional patients with this condition, which is also known as Lou Gehring’s disease, are being evaluated for possible participation in the trial at U-M and Emory University. This phase 2 trial is approved by the US Food and Drug Administration (US FDA) and is being funded by a Maryland-based company called Neuralstem, Inc., the proprietor of this stem cell product.

Neuralstem, Inc., has developed a neural stem cell line called NSI-566. When injected into the central nervous system of a living animal, these cells will divide up to 60 times and differentiate into a variety of neural cells (neurons, glial cells, etc.). Several publications have shown that injected NSI-566 cells survive when injected into the spinal cord, differentiate into several different neural cell types, and successfully integrate into the presently existing neural network.

In ALS patients, motor neurons progressively die off in the spinal cord, which limits voluntary movement.  ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord, leading to complete paralysis, and eventually, death. According to the ALS Association, as many as 30,000 Americans have the disease, and about 5,600 people in the U.S. are diagnosed with ALS each year.  The goal of this treatment strategy is to stabilize ALS patients and to replace dead or dying neurons and to slow the progressive decline and loss of movements, walking, and eventually breathing.

Eva Feldman, professor of neurology at the U-M Medical School, is the principal investigator for this clinical trial, and serves as an unpaid consultant to Neuralstem, Inc.  Dr. Feldman led the analysis of the results from the Phase 1 trial, which ended in 2012.  In this Phase 1 trial, 100,000 cells were delivered to each patient, and the patients tolerated them well and experienced to severe side effects.  One subgroup of patients seemed to experience interruption of the progression of ALS symptoms.

Feldman commented, “We’re going to be permitted to give more injections and more stem cells, in Phase 2.  We’re very excited that we have been able to bring this important work to the University of Michigan.”

Parag Patil, a neurosurgeon and biomedical engineer, performed both operations on the trial participants.  In each case, the patient’s spinal column was unroofed and the spinal cord exposed to receive the cells.  The stem cells are then introduced by means of a custom-designed delivery device that is affixed to the subject’s spinal bones so that it moves with the patient’s breathing throughout the process.

Neuralstem spinal cord injection device

Patil, as assistant professor, also serves as a paid engineering consultant to Neuralstem, Inc., in order to further prefect the injection device.  A third participant in this clinical trial received a stem cell injection in September at Emory University in Atlanta, Georgia.  This Phase 2 dose escalation trial is designed to treat up to 15 ambulatory patients in five different dosing cohorts, and will do so under an accelerated dosing and treatment schedule.  The first 12 patients will be divided into four cohorts and each will receive injections only in the cervical region of the spinal cord, where breathing function is controlled.

The first cohort of three patients received 10 cervical region injections of 200,000 stem cells per injection.  The trial will now progress to a maximum of 20 cervical injections of up to 400,000 stem cells per injection.  The last three Phase 2 patients will receive injections into the cervical and lumbar spinal regions, and will receive 20 injections of 400,000 cells in the lumbar region in addition to the cervical injections they have already received.  The trial also accelerates the treat schedule, and is designed to progress at the rate of one cohort per month with one month observations periods between cohorts.  Researchers expect all of the patients could be treated by the end of the second quarter in 2014.
Lumbar and Cervical

FDA green lights stem cell clinical trial for Lou Gehrig’s disease

Lou Gehrig’s Disease is a really nasty disease. The patient experiences a progressive degeneration of the nervous system that affects the brain and the spinal cord. The progressive degeneration destroys the nerves that help move muscles and causes a gradual loss of the ability to move. It eventually leads to the death of those neurons. Paralysis slowly sets in right before the patient’s eyes. Then other basic abilities slowly leave, like the ability to talk, void the bladder, control bowel movements and so on. It kills its victims slowly and horribly.

Neuralstem, a company in Rockville, Maryland, has received US Food and Drug Administration (FDA) permission to test spinal cord stem cells in twelve patients with Lou Gehrig’s disease (amyotrophic lateral sclerosis).  This approval comes approximately one month after the FDA placed Geron’s planned clinical trial on hold for a second time. Neuralstem’s trial had also previously been placed on hold by the FDA in February before it received the go-ahead in September.

Though both trials involve placing cells into the spinal cord, Neuralstem’s product is made of cultured neural stem cells derived from a single eight-week-old fetus, whereas Geron’s product, intended to treat spinal cord injury, is derived from embryonic stem cells that have been differentiated into precursors of neuron-support cells.

Lucie Bruijn, a scientist at the ALS Association stated that this is the first stem cell approach for Lou Gehrig Disease.  The chief science office at Neuralstem, Karl Johe, says tests of large animal models show that the transplanted neural stem cells are able to protect motor neurons, although, it’s not entirely clear how.  Neuralstem and their collaborators showed in a rat model of Lou Gehrig’s Disease that transplanted cells could develop into interneurons that formed connections with the rats” motor neurons.

Nevertheless, this approved trial will assess safety rather than efficacy. The first few patients selected for the procedure will be those who are no longer able to walk.  Since the injected cells protect rather than replace motor neurons, these sicker patients are less likely to benefit from treatment, but they are also less able to lose function if something goes wrong. Cells will be injected only on one side of the spinal cord in order to minimize the number of injection sites. Only one patient will be treated each month so that researchers can monitor effects over a longer period of time. According to Johe, the goal is to be able to inject cells in both lower and upper regions of the spinal cord in healthier patients and see if the injections can help motor neurons survive.

Other companies using neural cells include ReNeuron, which received permission from UK authorities this January to start clinical trials for stroke. Its cell product is made from genetically modified cultures of neural stem cells, also of fetal origin.

StemCells Inc. is conducting trials in Batten disease, a neurodegenerative disorder that strikes children, and recently received approval for a clinical trial in a similar disease. It also uses neural stem cells from material originally derived from fetuses and has recently published research showing that its cell product delayed some symptoms of the disease by about three weeks.

It is really a shame that fetuses had to die to give us these cells.  I know that people will argue that the mother’s decision to “terminate her pregnancy” had nothing to do with the use of this person’s cells for research, but the fact remains that a doctor probably killed this very young baby and now his or her neural stem cells are being used in clinics.  Is this the way to value the youngest and most valuable members of our society?  Forgive me, but I find this shameful.

There is another experimental treatment that does not need to use dead babies.  It uses mesenchymal stem cells derived from the patients who receive them.  Read more about it here.