In the pipeline and on the horizon.

Today, there are some new ways to control what MS does. By the time this magazine appears, the two approved drugs shown to alter the natural course of MS (Betaseron and Avonex) may well have been joined by a third, Copaxone, manufactured by Teva/Marion Partners. (See INSIDE MS, Fall 1995, page 9, or contact Teva/Marion Partners. Telephone, 1-800-840-5601; fax, 617-356-2998.)

In the pipeline now:

* Linomide (Roquinimex), manufactured by Pharmacia & Upjohn. 616-833-5367.

Individuals with. secondary progressive and relapsing-remitting MS are in a large multicenter trial, following two smaller trials that indicated this drug is safe for human use. It too may slow progression of MS, lower the number of brain lesions (inflamed and demylinated areas) seen on MRI, and reduce the number of acute attacks.

Form: pill, once a day

Side effects: headache, muscle and joint discomfort; less common but more serious, inflammation of membranes around the heart (pericarditis) or the lungs (pleuritis)

What it does: This medication suppresses or tamps down immunesystem activity.

* Interferon beta-1b (Betaseron), manufactured by Berlex Laboratories. 1-800-788-1467.

A three-year trial of Betaseron in people with secondary progressive MS is now in progress to determine if this drug can slow or stop the progression of disability. The study will also examine the safety and usefulness of adjusting dosage to the size of an individual's body-surface area.

Form: injection, under the skin, every other day

Side effects: flu-like symptoms following injection, which tend to abate over time; skin reactions at the injection sites

What it does: The effects of the product on the immune system are not yet completely understood.

* Oral myelin (Myloral) manufactured by AutoImmune Inc. 617-860-0710.

A two-year trial of Myloral in people with relapsing-remitting MS is near completion. Earlier studies suggested that a modest effect reducing the number and duration of MS attacks is somewhat stronger in people who lack a gene involved in immune response called DR2, and in men.

Form: pills, daily

Side effects: none reported

What it does; Powdered cow myelin, taken orally, may harness the body's ability to tolerate foreign proteins that are eaten -- and thus make the person's immune system stop attacking a similar protein -- one found in their own myelin.

A new spasticity medication:

* Tizanidine HC1 (Zanaflex), manufactured by Athena Neurosciences, Inc. (Note: Athena will not answer questions until the F.D.A. has formally approved their product.)

The stiffness, muscle spasms, and pain of spasticity plague many people with MS. Treatment includes physical therapy, stretching, and medications. Several medications, notably baclofen, are effective but may cause weakness.

Multicenter trials of Zanaflex, completed in the U.S. and Europe, indicate it can reduce spasticity without decreasing muscle strength. F.D.A. approval for marketing in the U.S. is expected.

Form: pills, 3 times a day

Side effects: drowsiness; dry mouth; fatigue; dizziness

Some even newer possibilities:

In laboratory studies, genetically engineered copies of specific antibodies (called monoclonal antibodies) stopped inflammatory immune cells from crossing the blood-brain barrier and entering the central nervous system -- a critical early step in the MS assault on myelin.

Recently, two separate pharmaceutical companies, Athena Neurosciences, Inc., and ICOS Corporation of Bothell, Wash. [telephone: [phone]; e-mail: [e-mail]; fax: [phone]], have developed different monoclonal antibodies and conducted pilot safety studies in small groups of volunteers. Both firms plan to conduct wider clinical trials beginning in: late 1996 or early 1997.

Peptide vaccines designed to block the unique cell-surface receptors that permit immune cells to react against the body's own tissues are also under study. Research published in the October 1996 issue of Nature Medicine suggests that this approach may eventually be useful in treating progressive MS.

Progress in Finding the Cause of MS

Genetic susceptibility..

Results from a major collaborative project on the role genes play in making an individual susceptible to MS were published in the science journal Nature Genetics in August. Work by researchers in the U.S., Canada, France, Great Britain, and Finland is included.

A U.S. team, lead by Dr. Stephen Hauser, in a four-year study funded by the Society, examined DNA patterns in over 50 families in which more than one member has MS. This team and three others identified a number of regions on several human chromosomes that influence susceptibility to MS.

One region, identified in two of the studies, is a subsection of chromosome 6, which houses genes already known to determine what molecules the immune system will attack. (The region is called the HLA, for Human Leukocyte Antigen, or the MHC, for Major Histocompatibility Complex.) Other research groups in this international effort have ruled out some previously suspected gene regions.

It is as if detectives in a worldwide manhunt have learned the names of several cities where the wanted criminals live. Now they must uncover street addresses and apartment numbers, and try to rule out the possibility that other collaborating criminals live in other cities.

... Plus an infectious trigger?

Susceptibility to a disease is not the whole story. Something must trigger the development of MS in a susceptible person. New evidence from an NMSS-funded team lead by Dr. Kai Wucherpfennig and Dr. Jack Strominger supports the idea that common viruses and bacteria (to which almost everyone is exposed) may be involved.

The studies showed that the same immune cells from people with MS that react against their own nerve-insulating myelin also react against four common virus families: influenza virus, human papillo-mavirus, herpes simplex virus (the herpes that causes cold sores); and reovirus, as well as a bacterium often implicated in urinary tract infections. This cross-sensitivity is an intriguing clue. Research is needed to learn more.