By David N. Leff
Editor¿s note: Science Scan is a roundup of recently published biotechnology-relevant research.
In the media, the term ¿VIP¿ denotes a ¿very important person.¿ In another venue, VIP stands for ¿vasoactive intestinal peptide,¿ which here is presented as highly effective therapy for rheumatoid arthritis (RA).
This autoimmune inflammation of the joints has no known cause, and no effective treatment. Around 1 percent of the adult population ¿ women outnumber men ¿ suffers from RA, which can lead to severe disability, and in extreme cases, death. Typical symptoms are pain, swelling, stiffness and loss of function in small joints, primarily those of the wrist and hand, as well as feet. Treatment is limited to pain relief.
The inflammatory process is fueled by an influx of well-meaning but ill-advised cytokines, unleashed by the body¿s immune system to fight infection, but crippling the inflamed joints they perceive as foreign invaders.
This frustrating scenario may change if a paper in the May 2001 issue of Nature Medicine bears fruit. It¿s titled: ¿Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease.¿ Its authors are cell biologists at Complutense University in Madrid, Spain.
Unfortunately for researchers, mice don¿t contract RA, but they can model the disease when immunized with antigenic bovine collagen II. Paw swelling and eventual destruction of cartilage and bone are measurable indicators of the experimental collagen-induced arthritis (CIA). After instigating this demonstration-model CIA in their mice, the co-authors administered VIP intraperitoneally on alternate days for two weeks. ¿Mice treated with VIP,¿ they report, ¿showed delayed onset, lower incidence and decreased severity of CIA in comparison with untreated arthritic mice.¿
Of late, innovative therapies have been tried, particularly to curb the excesses of tumor necrosis factor (TNF), orchestra leader of the immune system¿s inflammatory cytokine cascade. But however rational, these trials failed to alleviate signs and symptoms in a significant percentage of patients.
Two T-lymphocyte subsets of the immune system¿s cellular arm are apparently at work in the Spanish scientists¿ VIP treatment. They are T helper cells 1 and 2 ¿ Th1 and Th2 for short. Subset 1 T cells, which synthesize gamma interferon and interleukins, have a hand in cell-mediated ¿ cytolytic ¿ immunity, while Subset 2 T cells, which secrete other interleukins, are involved in immunoglobulin ¿ antibody ¿ synthesis.
Recently, low levels of Th1 cytokines have been found lurking in the synovial (joint-lining) tissue of RA patients, but few or no Th2 cytokines showed up. Therefore, enhancement of Th2 function and suppression of Th 1 cells have been proposed as a therapeutic approach to RA. The Spanish findings, says a commentary accompanying their article, ¿support this hypothesis by demonstrating that VIP treatment dramatically suppresses clinical joint diseases in murine CIA.¿
Congenital Neurodegenerative Muscle-Wasting Disease Improves With Nutritional Enrichment
Spinal muscular atrophy (SMA) is the leading genetic killer of children under the age of 2. In later life, it afflicts one in 6,000 to 10,000 people with muscle weakness and wasting ¿ mostly in the limbs. SMA victims have a genetic deficiency in a protein called SMN ¿ survival of motor neurons. These are the nerve cells that control the activity of muscles. When SMN protein levels are too low, motor neurons degenerate, leaving the body¿s major muscle groups helpless.
Biochemists at the University of Pennsylvania in Philadelphia observed that SMN will do its job efficiently if the proteins it needs to bind are first tagged by specific enzymes. The tags consist of methyl groups attached through the amino acid arginine to specific sites on SMN¿s protein targets. These methylation groups derive from folic acid, a member of the vitamin B12 complex.
The scientists propose that B vitamins ¿ rich in vegetables, grains and fruits ¿ may lessen, if only slightly, the severity of SMA. They report this finding in the May 2001 issue of the journal Molecular Cell, under the title: ¿SMN, the product of the spinal muscular atrophy gene, binds preferentially to dimethylarginine-containing protein targets.¿
Hippocampus, Center Of Memory, Cognition, Regenerated By Gene Therapy After Injury
Because the brain¿s hippocampus is famously a center of memory and cognition, this small, curly cerebral site is much studied by researchers of Alzheimer¿s disease (AD). Once damaged by ischemic stroke, seizures, toxins, the neuronal ravages of AD, or other insult, it¿s been commonly presumed that the hippocampus, like brain cells in general, can never regenerate its neurons.
However, a paper in the Proceedings of the National Academy of Sciences (PNAS), dated May 5, 2001, reports that fibroblast growth factor (FGF-2) promotes proliferation of neuroprogenitor cells in culture, and is up-regulated within the insulted brain. It¿s titled: ¿FGF-2 regulation of neurogenesis in adult hippocampus after brain injury.¿ The article¿s authors are neuroscientists at Harvard-affiliated Massachusetts General Hospital.
They induced seizures and cerebral ischemia in knockout mice genetically lacking FGF-2, then restored the growth factor by gene delivery or direct injection. Their conclusion: ¿Supplementation of FGF-2 in the brain after injury should help promote neurogenesis, and this can be achieved by gene delivery.¿
NASA, NCI To Develop Bio-Sensors For Applications In Outer Space, Inner Space
A year ago, NASA (the National Aeronautics and Space Administration) and NCI (National Cancer Institute) contracted to join forces on developing biomolecular sensors. Details appear in Science dated April 20, 2001, titled: ¿The NASA-NCI collaboration on biomolecular sensors.¿
Their combined efforts will extend from detecting life on other planets to designing minimally invasive sensing of early molecular signs of cancer in patients. It will cover diagnosis and treatment of injury and emerging disease in astronauts during long-duration space missions.