Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Multiple sclerosis afflicts some 330,000 patients in the U.S., a million worldwide. It's an autoimmune, demyelinating disease that strips the protective myelin sheath off neuronal axons. This causes progressive paralysis, muscular tremors, numbness, itching, color-blindness, double vision and loss of eyesight, severely impaired coordination or balance and loss of cognition.

However, these grave signs and symptoms don't progress inexorably to a climax; rather, they come and go, with irregular flare-ups and remissions. This unpredictable, aberrant pattern confounds both the diagnosis and understanding of MS.

Stanford University neurologists resort to two research modalities to probe MS - one traditional, the other ultra-modern. The former is an autoimmune, demyelinating disease called experimental autoimmune encephalomyelitis - EAE for short - which closely mimics in laboratory animals the signs and symptoms of human MS. The up-to-date insights rely on microarray plate analysis (chips) of tissue from neuronal lesions that occur in MS patients.

Their results, reported in Nature Medicine for May 2002, carry the title: "Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis."

Comparison of two poles of MS pathology — acute lesions with inflammation vs. "silent" lesions without inflammation - revealed differentially transcribed genes, their paper states. Some products of these genes were chosen as targets for therapy of experimental autoimmune encephalomyelitis in mice. Taken together, these results "elucidate new aspects of pathology and open possibilities for therapy."

Using cytokine treatment or targeted gene disruption, the Stanford team was able to alleviate symptoms in an EAE mouse model. The authors foresee that this first description supporting molecular differences in the two types of lesions could ultimately influence the choice of treatment for acute vs. chronic stages of the MS disease.

A "News & Views" commentary accompanying the journal article noted, "In humans, the inability to collect brain or spinal cord biopsies from MS patients has hindered our understanding of the initiation and progression of the disease. Furthermore, a scarcity of post-mortem tissue has impeded analysis of the late stage of MS, as scientists have been unable to garner substantial information from the tissues made available."

Microarray chips enabled the co-authors to bridge somewhat that animal-human gap. They compared post-mortem neuronal tissue from four MS patients with specimens from two non-MS individuals. That demonstrated that 39 genes had increased expression in all MS lesions, whereas 49 genes had decreased expression. Those findings pointed in detail to possible therapeutic approaches.

Streptomyces coelicor, Antibacterial Source, At 8,667,507 bp Is Biggest Bug Sequenced To Date

On May 8, a press conference in London announced the largest completely sequenced bacterial genome, Streptomyces coelicor, which weighed in at 8,667,507 base pairs. This filamentous, soil-dwelling bacterium yields most natural antibiotics used in human and veterinary medicine. At 7,825, its genome contains the largest number of genes so far discovered in a bacterium. Its analysis revealed an ancient synteny (the relationship between two genetic loci on the same chromosomal pair) between the central "core" of S. coelicor's linear chromosome and whole chromosomes of two bacterial pathogens - Mycobacterium tuberculosis and Corynebacterium diphtheriae.

Nature, dated May 9, 2002, reported the record feat under a paper titled: "Complete genome sequence of the model actinomycete Streptomyces coelicor A3." Its principal co-authors are at the John Innes Center in Norwich and the Sanger Institute in Cambridge, UK.

They observed, "The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of now much-needed antimicrobial drug candidates by genetic engineering. The importance of streptomycetes to medicine results from their production of over two-thirds of naturally derived antibiotics in current use [and many other pharmaceuticals such as antitumor agents and immunosuppressants]. Furthermore, they are members of the same taxonomic order as the causative agents of tuberculosis and diphtheria.

"With 7,825 predicted genes," their paper continued, "the S. coelicor chromosome has an enormous coding potential. This number compared with 4,289 genes in the Gram-negative bacterium Escherichia coli, 4,099 in the Gram-positive, spore-former Bacillus subtilis, 6,208 in the lower eukaryote [baker's yeast] Saccharomyces cerevisiae, and a predicted 31,780 in humans [Homo sapiens]."

Myostatin, Driver Of Muscle Wasting, Seen As Target For Cachexia-Curbing Drugs

Cachexia is a disorder marked by general weight loss and wasting in the course of a chronic disease or emotional disturbance. Myostatin is a protein that fuels cachexia by thwarting the growth of muscle tissue. Patients with chronic diseases such as cancer and AIDS often develop this life-threatening, poorly understood malady.

A paper in Science dated May 24, 2002, describes "Induction of cachexia in mice by systemically administered myostatin." Its co-authors, at Johns Hopkins University School of Medicine in Baltimore, discovered myostatin in the 1990s. (See BioWorld Today, May 7, 1997, p. 1.)

They see myostatin as a target for putative drugs that may help to prevent or treat the disease in humans.

The paper points out that cattle genetically deficient in myostatin exhibit dramatic increases in skeletal muscle mass. It grants that whether this enhanced muscling results from prenatal or postnatal lack of myostatin is unknown.

In in vivo experiments, mutant mice whose cells produce too much myostatin lost an average 33 percent of their body weight, even though they ate normally. Proteins that blocked myostatin's activity slowed the weight loss. In knockout mice lacking myostatin, individual muscles weighed 100 percent to 200 percent more than control animals. The paper notes that even though myostatin does not appear essential for either viability or fertility, it "has been remarkably well preserved through evolution; human, rat, murine, porcine, turkey and chicken myostatin protein sequences are identical in the COOH terminus of the protein."