Human Stem Cells Battle Degenerative Brain Diseases

Human Stem Cells Battle Degenerative Brain Diseases
   Embryonic and adult stem cells offer similar protection against neurodegenerative disease, according to a landmark study in mice, which has achieved a number of firsts with human stem cells. For the first time, rodents genetically predisposed to disease lived longer and healthier lives after receiving injections of the human cells, researchers claim. "We have been talking about stem cells for a decade and no one had cured anything with stem cells before this," comments Eva Mezey, a researcher at the National Institutes of Health in Bethesda, Maryland, US, who was not involved in the work.
    In the new study, Evan Snyder of the Burnham Institute for Medical Research in La Jolla, California, US, and colleagues studied mice with a mutation in a gene called Hex. This mutation leads to a deficiency in an enzyme that breaks down fatty substances called lipids. As a result, these lipid molecules accumulate in the brain and spinal cord, destroying cells and causing the loss control over body movement. Mice with the disorder die prematurely, at around 120 days of age. In humans, similar mutations in the Hex gene lead to illnesses such as Tay Sachs disease and Sandhoff’s disease, which lead to death within the first few years of life because no treatment exists. Delayed onset A day after birth, the mice carrying mutant Hex genes received brain injections of human stem cells taken from discarded human embryos. Snyder’s team also injected a separate group of the mutant mice with stem cells taken from the brains of aborted human fetuses, which are sometimes referred to as "adult" stem cells because they can only develop into a limited subset of cells. The cell transplants seemed to delay onset of disease in the rodents. Both groups of mice that received human cells retained normal control over body movement for about 119 days, three weeks longer than the untreated mice.
More strikingly, the mice with the transplanted human cells lived to about 160 days – 36% longer than their untreated counterparts, who died at 110 days on average. However this is still well short of the average lifespan of a normal, healthy mouse, which is roughly two years. Examinations of the rodent’s brains revealed that the human cells had developed into signaling nerve cells, offering the first evidence that such cells can integrate into the brain circuitry of diseased animals following transplantation.
    Combination approach: However, the scientists stress that the nerve signaling of the human embryonic stem cells could not on its own account for the benefit seen in the animals. They say the stem cells also released the enzyme that breaks down the excess lipids. Mice that received human stem cell injections and a drug that boosts the action of this enzyme lived 70% longer than their untreated counterparts. And Snyder believes that giving the animals continuous doses of stem cells throughout could extend their lifespan even further. A combination of these approaches might one day work in humans, he suggests. "I think this is a landmark study," says Robert Steiner at the Oregon Health Sciences University School of Medicine in Portland, US. The work is an "elegant example of the therapeutic potential of stem cells", he adds.
Ethical concerns: The fact that the embryonic stem cells did as well as the "adult" stem cells intrigued scientists, as the latter is seen by some as more ethically acceptable for use in medicine. "It’s interesting that one could use a variety of cell types and see similar efficacy in the mice," says Steiner, who is currently leading a clinical trial using human stem cells to treat children with a brain disease known as Neuronal Ceroid Lipofuscinoses (NCL). But Snyder notes it is much easier to cultivate stocks of embryonic stem cells for medical use: "They just grow quicker and in greater quantities." Another notable aspect of the experiments was that the mice did not receive drugs to suppress their immune systems, suggesting that stem cell transplants might be well tolerated in humans without such medication. Furthermore, none of the animals developed cancer, a potential problem that concerns stem cell researchers. Experts say this is encouraging, especially since the mice lived into an age where such complications typically occur. "We can never be sure, but some of the mice lived well into adulthood," says Mezay, who studies the potential of stem cells to repair brain damage.
    Long tunnel: Snyder hopes to apply for government approval in the next few months to try using stem cells to treat children born with Tay Sachs and Sandhoff’s disease. But experts caution that parents of such children should not expect a workable treatment soon. "It’s a light at the end of the tunnel," Mezey says of the positive results, "but the tunnel is very long". Larry Goldstein, at the Howard Hughes Medical Institute in La Jolla, adds: "There’s a lot of work to go from a mouse study to a human clinical trial." The new study also bolsters hopes that scientists might one day succeed in using stem cells to treat more complicated illnesses, such as Alzheimer’s and Parkinson’s disease. "But those are harder to tackle in that we don’t always know what to fix," says Snyder. Other scientists agree. "That’s a leap – Tay Sachs and Sandhoff’s are quite different from diseases that develop when you are 60 or 70 years old and going downhill – and your body is much less flexible," says Mezay.
--Roxanne Khamsi 11:14 12 March 2007 ; NewScientist.com news service

* Read official Burnham Institute Press Release or related articles in the San Diego Union Tribune, North County Times , or the North County Star Ledger

Article: Lee JP, Jeyakumar M, Gonzalez R, Takahashi H, Lee PJ, Baek RC, Clark D, Rose H, Fu G, Clarke J, McKercher S, Meerloo J, Muller FJ, Park KI, Butters TD, Dwek RA, Schwartz P, Tong G, Wenger D, Lipton SA, Seyfried TN, Platt FM, Snyder EY.Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease. Nat Med. 2007 Mar 11