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.

FDA Negotiates with Geron to End Hold

Geron Corporation has negotiated with the Food and Drug Administration to continue their Phase I trial with their embryonic stem cell-derived cell line GRNOPC[1].  To refresh your memories, As announced previously, in one preclinical study, in a preclinical study, Geron scientists saw a higher frequency of cysts in animals treated with GRNOPC[1] cells.  These cysts formed in the injury site, do not grow (are non-proliferative), are confined to the injury site, are smaller than the injury cavity, and do not seem to cause any adverse effects in the animals.  The FDA placed a hold on Geron’s Investigational New Drug Application in response to these data.

Geron apparently made a deal with the FDA to continue preclinical studies with some “new markers and assays” as agreed upon in discussions with the FDA.  Geron also said in their news release that as a “part of the ongoing plan to advance clinical development to cervical patients, Geron had already initiated this preclinical study in an animal model of cervical injury.”  They also say that Geron hopes that the study will be re-initiated in the third quarter of 2010.

Geron hopes to use their cell line to treat spinal cord injury to the cervical (upper) portion of the spinal cord as well as the thoracic (middle) portion of the spinal cord.

I hope that Geron gets this off the ground.  They have worked very hard and if their cell line helps people with spinal cord injury, then that’s great.  However what I hope we do not see are more embryos killed so that others can experiment with their cells.  In the case of Geron’s cell line, the embryos were killed long ago.  Whining about it seems to be completely counterproductive.  However if these cells can help people, then great.

We should not be surprised that there are concerns with these treatments.  It is after all, the first of its kind.  There are bound to be glitches.

Embryonic Stem Cell Lines Accumulate Cancer-Causing Mutations

Embryonic stem cells have an incredible ability to grow in culture. Their ability to fill a culture dish in a short period of time makes them attractive candidates for regenerative medicine. However, embryonic stem cells bring a caveat to the table as well. They can sometimes form tumors. Many times these tumors are not aggressive, but sometimes they are. If embryonic stem cells are differentiated into tissues, their ability to grow and form tumors decreases, but does not completely disappear. There are plenty of cases where cells made from embryonic stem cells do not produce tumors when transplanted into animal hosts, but there are also several cases where even cells differentiated from embryonic stem cells can produce tumors.

Because scientists want to grow embryonic stem cell lines in the laboratory, they will grow them in cultures for long periods of time. However, growing human embryonic stem cells for long periods of time can cause the cell line to show chromosomal instability while being cultured continuously (Hanson C, Caisander G. Human embryonic stem cells and chromosome stability. APMIS. 2005 Nov-Dec; 113 (11-12): 751-5). Long-term growth of human embryonic stem (hES) cells in the laboratory can cause them to gain or lose large sections of chromosomes. According to several reports in Nature Biotechnology, this instability can lessen the reproducibility and reliability of experimental results, and can raise the specter of cancer, which can hinder the clinical application of embryonic stem cells.

Anselme Perrier and his colleagues of The Institute for Stem Cell Therapy in Evry, France discovered that long-term culture of five hES cell lines resulted in a the amplification of a portion of a the 20th chromosome called 20q.11.21 locus in four cases of the five cases (Nature Biotechnology 26, 1364 – 1366, 2008). This portion of the human genome contains 23 genes, many of which have roles in proliferation and cell survival.  Therefore, this amplification may give cells a selective advantage and therefore become more prevalent over time.

In a complementary study, Dr Claudia Spits of Vrije Universiteit Brussel in Belgium examined 17 different hES cell lines with her colleagues and showed the same amplification in five cases (Nature Biotechnology 26, 1361 – 1363, 2008).  A part of chromosome 18 was amplified in three cell lines and had several trisomies (three copies of a chromosome) and monosomies (one copy of a chromosome) as well.  The deletion of part of chromosome 18 led to rapid increase of cell growth, indicating that there may be a tumour suppressor in that area. “It’s still an early stage” says Spits, who intends to look further at chromosome 18. “The potentially oncogenic genes that lie in areas that are amplified or duplicated are not well characterized yet, but they have been found in a number of cancers.”

What are we to make of this?  Simply put, if embryonic stem cells are going to be used in a clinical setting, then they should be made and used within a short period of time.  Culturing them for long periods of time should be avoided, since this selects for cells that grow uncontrollably.  This might not be practical, but I think that there is enough evidence to suggest that making lines and culturing them for long periods should be taboo for clinically used lines.