But progress in the development of stem cell therapies for spinal cord injuries is also pushing ahead. While a Portuguese doctor treats American spine-injury patients with adult stem cells, with apparent (but scientifically unproven) results, a US researcher has been achieving similar success using human embryonic cells in spine-injured rats.

In another approach that could lead to treatments for spinal cord injury and neurodegenerative disorders, neuron precursor (stem) cells pre-existing in the brain have been induced to replace damaged neurons in mice. Specialized stem cells genetically modified to produce a cancer drug have been shown in mice to target human tumors without causing toxic side effects. Clinical trials are being planned.

Stem cell therapy is not totally moribund in the US, not even in Mr. Bush’s home state of Texas, where another use of stem cells is under investigation to treat ovarian cancer. While it is still not scientifically proven that stem cell therapy works, a patient’s shattered skull was made whole when it was used. Baby teeth harbor stem cells that may be more versatile, and certainly less controversial, than embryonic stem cells for therapeutic use.

Genetics research is also gathering steam, as evidenced by pharmaceutical giants moving into biotech turf. Novartis is one example, developing an ambitious biotech program. All this activity in genetics is showing signs of success: A possible gene therapy for age-related hearing loss, for example, is showing promise, and the discovery of the “master gene” that switches on key properties of other oncogenes may be a big step toward a single drug to cure or control multiple forms of cancer.

Removing a gene (or deactivating the protein it governs) responsible for slowing down the conversion of fat to energy could enable us stay slim while eating all we want. It has worked in mice, and humans have the same gene. Presumably one would not want this modification in times of famine.

Another step toward personalized medicine comes in the form of a genetic test, approved in Europe and now the US, that determines ideal medication dosages for the individual patient.

Other therapeutics-related developments:

• Engineered cardiac tissueunder development could, if it works, be an alternative to stem cell therapy, if that doesn’t work, for the heart.
• Plastic surgery for serious facial injuries advances with a new structural material.
• Nanotechnology is key to another approach to targeted cancer drug therapyunder development in Australia and the US.
• An epileptic anticonvulsant gives worms 50 percent more life.
• A drug is under development that could cure type 2 diabetes.

Medtronic has licensed polymer technology developed at Purdue University that can prevent paralysis in dogs with hours- or days-old spinal cord injuries. It will take at least two years before the polyethylene glycol (PEG) technology is ready for human clinical trials. Already used in cosmetics and as a laxative, PEG is though to repair holes in damaged cell membranes and “stitch” severed cells back together.

Sixty-eight percent of dogs admitted to two veterinary hospitals with paraplegia caused by compressed spinal cord nerve fibers and treated with intravenous injections of PEG followed by standard treatments were able to walk within six weeks, compared with only 24 percent of the historical controls. In 63 percent of dogs at one of the hospitals tested for nerve conduction between brain and leg, normal conduction was observed, versus only about eight percent in the historical control group. Conduction has previously been restored in guinea pig spinal cords that had been completely cut through.

Reference: Callahan, Rick (2004). “Medtronic unit signs deal with Purdue.” Associated Press via Star Tribune, December 28.

Reference: Farley, Peter (2004). “Spine-damaged canines made to heal.” New Scientist, December 3.

Spinal Cord Therapy from Lampreys

Paralysis resulting from spinal cord injuries often occurs because the brain is cut off central pattern generators (CPGs), “networks of neurons in the spinal cord that are thought to produce an automatic walking motion in toddlers or allow a chicken to run around without its head,” writes Karen Lurie in Wired. Researchers at Johns Hopkins University and the University of Maryland are developing artificial CPGs to “kick start those circuits and then fine-tune the behavior of those circuits that already pre-exist in the spinal cord,” one of the researchers told her.

With funding from the US Office of Naval Research, the National Science Foundation, and the National Institutes of Health, the team has already created an “adaptive CPG” microchip that can control robotic locomotion. It contains a silicon analog of spinal circuits modeled from the lamprey spinal cord. With it, the researchers were able to control a biped robot. It is “adaptive” because it uses feedback from the joint angles and foot-falls of the robot to arrive at smooth and natural gait.

A neuroprosthetic implant for humans, that would communicate directly with the circuits in the spinal cord, is at least a decade away, but a temporary device might be activated by a user-controlled joystick or buttons to move their legs forward or to turn.

Reference: Lurie, Karen (2004). “Lamprey May Offer Paralysis Cure.” Wired News, December 14. http://www.wired.com/news/medtech/0,1286,66005,00.html

Stem Cell Therapy Repairs Spinal Cord in Rats

A University of California researcher has made paralyzed rats to walk again by injecting them with healthy brain cells developed from human embryonic stem cells, and hopes to apply the therapy to humans by 2006. His method turns stem cells into specialized cells that help the brain’s signals traverse the spinal cord. Those new cells have repaired damaged rat spines several weeks after they were injured. He is now working with Geron Corp. to design phase 1 (safety) human clinical trials.

Reference: Elias, Paul (2004). “Stem Cell Researcher Makes Paralyzed Rats Walk.” Associated Press via Technology Review, December 20. http://www.technologyreview.com/articles/04/12/ap_3122004.asp?trk=nl

Stem Cell Brain/Spinal Cord Therapy

By killing corticospinal motor neurons in the brains of mice, Harvard scientists induced nearby stem cells (in the subventricular zone) to migrate to the damaged site and create replacements that not only took up proper locations within the brain, but reconnected to the spinal cord. The goal is to find new ways to grow neurons, which would help researchers identify key molecules involved with neuron birth and translate them into drugs.

The technique could be applied to treat spinal cord injury or neurological diseases including Alzheimer’s, Parkinson’s and Lou Gehrig’s, and would avoid immune and other complications that might result from stem cell transplantation.

Reference: Philipkoski, Kristen (2004). “Mice Brains Can Fix Themselves.” Wired News, November 1. http://www.wired.com/news/medtech/0,1286,65560,00.html

Doc-in-a-Cell Treats Cancer

By inserting the interferon beta gene into mesenchymal stem cells from bone marrow then infusing the stem cells into mice, Texas researchers have successfully treated human cancers. The stem cells specifically targeted tumor cells and produced high concentrations of therapeutic proteins inside them, eliminating the toxic side effects of interferon beta. The drug also persisted longer than if administered directly.

Mesenchymal stem cells are activated naturally when new tissue is needed to heal wounds or form scars. Tumor cells appear to them as “never-healing wounds.” The engineered stem cells did not appear to enter healthy organs or tissue, though it is possible they could be “waylaid” by other wounds elsewhere in the body and thus prevented from reaching tumors.

Mice treated with the engineered human stem cells survived for 60 days, with interferon beta alone for 41 days, and without any treatment for 37 days. Mice with melanoma treated with the stem cells survived 73.5 days, compared with 30 days for untreated mice.

A human clinical trial application is under development.

Reference: Unknown (2004). “Stem Cells Take on Tumors.” Associated Press via Wired News, November 2. http://www.wired.com/news/medtech/0,1286,65573,00.html

Reference: Henderson, Diedtra (2004). “Scientists Tout Method of Attacking Tumors.” Associated Press via Yahoo News, November 3. http://www.healthleaders.com/news/newspage1.php?contentid=60026

Stem Cell Therapy for Ovarian Cancer

An ovarian cancer patient in remission for the second time is about to undergo experimental stem cell treatment at the M.D. Anderson Cancer Center in Houston, Texas. Stem cells from the patient’s bone marrow will be injected into her hip to “identify and then adapt to the weak spots in her body to possibly cure the cancer,” writes Natalie Lombardo in the Daily Oakland Press. Thirty percent of women in various stages of ovarian cancer s far treated with this procedure have had no recurrence after five years.

Reference: Lombardo, Natalie (2004). “Teacher seeks out stem cell transplant.” Daily Oakland Press, December 12.

Stem Cell Therapy Repairs Skull

German surgeons mixed stem cells from a 7-year-old girl’s fat with bits of her bone to help repair severe damage to her skull. It may be the first time that any kind of stem cell had been harnessed to regenerate bone in a human, though it cannot be claimed as proof that the stem cells produced the new bone.

The patient, injured in a fall two years before the surgery, was missing several areas of skull totaling nearly 19 square inches. Previous efforts to repair the holes were largely unsuccessful, but several weeks after the stem-cell surgery she was able to leave stop wearing her protective helmet. Her skull is now smooth and unbroken, the missing parts replaced by thin but solid bone.

Whether or not it was the stem cells that did the trick, the fact is that the therapy first did no harm and secondly it worked. Bone fragments were taken from the girl’s pelvis and about 1.5 ounces of fat tissue was taken from her buttocks. The bone was milled into chips about a tenth of an inch long and placed in the missing areas of the skull. Then surgeons then applied stem cells extracted from the fat to the bone chips.

Reference: Ritter, Malcolm (2004). “Stem cells from fat used to repair major skull injury, German doctors report.” Associated Press via Detrit News, December 18.

Stem Cells from Baby Teeth

Australian researchers propose that stem cells found in the pulp inside baby teeth could be used to “grow new teeth and perhaps even cure neurological disorders like Parkinson’s disease.” They could be used, said one, to grow replacement brain tissue to overcome stroke damage as well as basal cell degradation linked with Parkinson’s. They believe such stem cells would be more versatile than embryonic material, as well as more ethically acceptable, and have already begun injecting human baby tooth stem cells into rat brains to stimulate other brain cells to take over the functions of impaired tissue. Another team at the Adelaide University School of Dentistry is attempting to use the cells to grow replacement teeth in sheep.

Reference: Sandilands, Ben (2004). “Baby teeth provide life-giving stem cells.” New Zealand Herald, December 4.

Gene-Based Drug Research

Drug maker Novartis is focusing less on the traditional blockbuster drug paradigm and more on finding the genetic causes of diabetes, cystic fibrosis, tuberous sclerosis, and several other diseases, in order to create new drugs to treat them. The efforts are being concentrated in a new US$4 billion facility in Cambridge, Massachusetts, with contributory work continuing at Novartis labs in Switzerland, Japan, and New Jersey.

Reference: Whalen, Jeanne (2005). “Gene-Based Drug Research Takes Shape at Novartis.” Wall Street Journal, January 19.

Genetic Engineering to Cure Deafness?

Harvard Medical School researchers have discovered that deletion of a specific gene can lead to the proliferation of new hair cells. This could lead to treatment of age-related hearing loss by stimulating the growth of new hair cells in the inner ear.

However, more research is needed to refine the technique. Simply deleting the gene could result in uncontrolled cell growth and cancer. The key will be to switch off the gene just long enough to generate enough hair cells to restore hearing, and then to turn it back on again to avoid possible complications. Research is also needed to show that the regenerated hair cells actually improve hearing following damage to the cochlea.

Reference: Unknown (2005). “Hair cell hope for hearing loss.” BBC News, January 14.

“Pokemon” Master Oncogene

US researchers collaborating with teams in Japan and Britain say they have discovered the “master switch” for all forms of cancer. It is a gene that regulates critical aspects of all other oncogenes, including their acquisition of immortality. “Pokemon” (POK erythroid myeloid ontogenic factor), as they have called the gene, “is likely active in a wide range of cancers: breast, prostate, bladder and lung malignancies,” one of the researchers said. Thus, a signle drug developed to act on Pokemon could cure or control multiple forms of cancer.

Reference: Ricks, Delthia (2005). “‘Master’ gene seems to turn on cancer-causing action.” Newsday via Detroit News, January 21.

Obesity Cure

Australian researchers have genetically re-engineered a mouse to be able to eat all it can eat yet carry only half the normal amount of body fat. The re-engineering, which caused the mouse to burn energy at a much higher rate than normal, consisted of removing a gene that slows the conversion of fat to energy.

The re-engineered mice appeared to enjoy the same life-span as normal mice and were able to reproduce normally. Apart from the ability to eat more without gaining weight, the only noticeable physical changes were an increase in body temperature and energy levels.

Humans have the same gene, therefore the technique should in theory work for humans also. Genetic re-engineering might not be necessary: a drug that blocked the protein produced by the gene, that is actually proximately responsible for slowing down the fat-to-energy conversion, might suffice. Such a drug could be ready in about five years away and, say the researchers, would be most suited to obese people with a genetic disposition to developing type two diabetes.

Reference: Unknown (2004). “Hot mouse could lead to obesity cure.” Ananova, undated.

Personalized Medicine

A genetic test kit from Switzerland-based Roche enables physicians to personalize drug doses and enhance drug safety. The “AmpliChip CYP450” test analyzes variations in two genes that regulate an individual’s rate of absorption of drugs. The test helps determine correct dosages for the individual, and can also help prevent adverse drug interactions.

Reference: Greil, Anita (2005). “NEWS SNAP: Roche Gets FDA Approval For AmpliChip CYP450.” Wall Street Journal, January 11.

Growing a Beating Heart

Using electrical stimulation, MIT researchers have induced dime-sized clumps of rat cardiac cells grown on a three-dimensional, degradable collagen scaffold to beat. In short, they engineered tissue similar to that of a native heart.

A researcher at Duke University who has separately engineered functional human arteries is collaborating with the MIT team so that her engineered arteries can be incorporated into the engineered cardiac tissue.

If successful, this would be an alternative therapy to stem cell injections to repair damaged heart muscle.

Reference: Philipkoski, Kristen (2004). “A Patch for Broken Hearts.” Wired News, December 13.

New Plastic for Reconstructive Surgery

British and Russian researchers have created a polymer alternative to traditional titanium structures for facial reconstruction implants. The “PolyHap” implants are now being clinically trialed in Moscow to correct jaw or skull deformities in children with serious facial injuries. A trial surgeon said: “These implants allow us to carry out many more operations than before. They are easier to adjust and reshape and give us much more flexibility in our work.” The implants can be adapted for any part of the skeleton.

The researchers have now begun work on a biodegradable version of the polymer.

Reference: Edward, Rhiannon (2005). “Implant helps injured children to smile again.” The Scotsman, January 12.

Smart Bombs for Cancer

Nanoscale cancer drug capsules under development at the University of Melbourne in Australia are designed to find their way to a tumor then rupture when heated by a low energy laser pulse, delivering the drug exactly where it is needed and minimizing side effects. The polymer capsules contain gold nanoparticles attached to tumor-seeking antibodies. A pulse from a harmless “near-infrared” laser will melt the gold, rupturing the plastic capsules and releasing the contents. The laser would be able to penetrate a few millimetres of tissue. It could be shone through the skin, or be beamed inside the body through an endoscope.

In the US, a Rice University spinoff company appears to be using the same approach. Tumors in mice injected with the nanoparticles disappeared six days after the light treatment, while tumors in control-group mice grew quickly. There appeared to be no harmful side effects.

Reference: Reynolds, James (2005). “Smart bombs developed to target cancer tumours.” The Scotsman, January 6. http://news.scotsman.com/scitech.cfm?id=13282005

Reference: Lok, Corie (2004). “Cooking Tumors: Nanospectra Bioscience’s gold-plated particles heat and kill tumors.” Technology Review, November.

Anti-aging Drug

US researchers have discovered that an anticonvulsant used to fight epilepsy and two other similar human drug compounds can prolong the lives of C. elegans worms by as much as 50 percent. Doctors could start prescribing the anticonvulsants tomorrow because they are already approved for human use, but there could be unknown long-term risks. The researchers next plan to test the drugs in flies and mice, and to widen their search to other types of chemical.

Reference: Pearson, Helen (2005). “Epilepsy drug may delay ageing.” Nature, January 13.

Diabetes Drug

A private company spun off from Harvard Medical School research is developing a drug that activates the SIRT1 enzyme, which they believe could reverse the problem that underlies type 2 diabetes: cells’ inability to absorb glucose.

Reference: Lok, Corie (2005). “Change of Plans, Ponce de León.” Technology Review, January.