Dr. Richard Shubin from the Casa Colina’s Multiple Sclerosis Center in Pomona explains the latest advances in new medications:
In a cell biology lab at UC Riverside, researchers look at the four screens of a flow cytometer, a sophisticated instrument that searches for fluorescent labeled reactions inside cells.
Some cell activities will fluoresce green, red, yellow or some other color based on how the study is set up.
The computer-driven machine uses a laser to scan 5,000 cells per second in the search for understanding the relationship between neurons, the electricity-carrying cells of the nervous system, and the microglia, the cells that support the neurons, said Monica Carson, associate professor of biomedical sciences at UCR and director of UCR’s Center for Glial-Neuronal Interactions.
In multiple sclerosis patients, why do some microglia turn on the nervous system and attack the myelin sheath that protects neurons and speeds the conduction of electrical impulses?
When scientists understand this relationship, they can develop drugs to turn off the hostile behavior of microglia and other soldiers attacking the immune system, preventing the advance of multiple sclerosis, Carson said.
While Carson and researchers are looking for the ultimate understanding and ultimate cure for MS, others are fighting the battle with current knowledge and an arsenal of medicines that have been around for about 20 years.
Dr. Richard Shubin, who is program medical director of Casa Colina’s Multiple Sclerosis Center in Pomona, meets with patients at the center.
Shubin, a neurologist, also has a private practice in Arcadia and through his Pasadena-based research office, Neurotherapuetics, is engaged in trial studies for the three new medicines with MS fighting potential.
In three to five years, doctors will have a new arsenal of medications in the battle against the harmful effects of multiple sclerosis, Shubin said.
Included in this list is a group of drugs that can be taken in pill form, where all frontline drugs currently authorized are delivered either intravenously or via injections.
Most patients with MS now have treatment with one of four frontline drugs of roughly equal efficiency, Shubin said.
Three of them are in the interferon family of drugs, meaning they belong to a group that tweaks the immune system to turn off the characteristic MS trait of attacking the cells that make the myelin sheath.
Another drug, called Tysabri, is stronger than the interferon drugs but can have a serious side effect, leading to a viral infection of the brain called progressive multifocal leukoencephalopathy (PML), which is caused by activation of the JC virus, a bug carried by most people that is harmless except in immune system compromised individuals.
PML is most frequently seen in people with AIDS. Oddly, Shubin said, patients who have developed PML after treatment with Tysabri do not develop the other diseases characteristic of AIDS patients.
Because of this side effect, Shubin said Tysabri is not given to MS patients unless the other medications have not been successful in controlling the progression of symptoms.
Shubin said he believes that one of the new drugs with the most promise is FTY-720, or Fingloimod, a daily pill that is in the third phase of clinical study in multiple sites around the world.
In addition to the Pasadena site, the drug is being tested in other locations throughout North America, South America, Australia and Europe, Shubin said.
“For years patients have been asking for an oral medicine. So that development of pills will help improve quality of life and improve compliance,” he said.
If the trial delivers the expected results, the manufacturer will be able to apply for approvals from multiple countries around the world at the same time, Shubin said.
Campath is another one of the drugs in clinical trials. While it appears to be twice as effective as the interferons, it has potentially severe side effects, Shubin said.
“There is a tradeoff with greater potency. They work better but there are more side effects. Some people are calling this a neutron bomb because of its potency. It’s probably the most potent of the new drugs, but also potentially the most toxic.”
In earlier trials, some patients on Campath have developed Goodpasture’s syndrome, a condition leading to the rapid destruction of the kidneys and hemorrhaging of the lungs, he said.
Laquininod, a once-a-day pill, is another drug Shubin is working with under clinical trials.
“This may be the winner in terms of lack of side effects,” Shubin said.
There are several others in various phases of clinical trials as well.
Shubin said that when people are diagnosed with MS, their path is frequently a gradual worsening to the point that they are forced into a wheelchair after 15 years.
That time frame may be lengthened somewhat with medications, he said.
For some, however, the disease progresses much more rapidly and doctors are willing to use more aggressive medicines on them.
Although MS can strike at any age, the most common years for diagnosis are between 20 and 40. Women are three times more likely than men to have the disease.
This disease strikes different parts of the nervous system “without rhyme or reason,” Shubin said.
It can affect vision, the ability to think, bowel and bladder functions, coordination, walking, speech, cause numbness or burning sensations, or involuntary contractions. A commonly shared effect of the disease is fatigue.
“Imagine starting out every day feeling you were just getting over the flu,” he said.
Patients may have long periods of stability before their symptoms flare up. Some patients Shubin sees may visit him only once a year.
When MS patients experience a flare-up, they may rebound to life just as it was before the onslaught of symptoms. But as time goes on, patients don’t spring back.
Too much damage to the nervous system has occurred, Shubin said. Now, each flare-up will leave them in worse shape than before.
It’s the mystery of what causes those flare-ups that has Carson and her researchers running their tests. The next batch of cells analyzed by the flow cytometer could bring us a little closer to those answers.