Multiple sclerosis (MS) is not ME/CFS and ME/CFS is not MS – so why a blog on a promising drug for multiple sclerosis? Because even if the disorders are different – even dramatically different in some ways – enough similarities exist to suggest that common pathways could be operating in both.
In multiple sclerosis, a breakdown of the myelin sheaths covering the axons of the nerves in the brain and spinal cord causes impaired nerve signal transmission, difficulty with movement, strange sensations, and even paralysis. Fatigue, interestingly, is often the first symptom seen in the disorder.
Some evidence of impaired nervous system transmission is present in ME/CFS, but it’s not clear what is causing it, and it’s not on the scale seen in MS. The distinctive lesions that signal the loss of the myelin covers in the brains of MS patients are not present in ME/CFS patients. Key aspects of the fatigue found in each disorder may be different as well.
More women than men get both disorders, however, and infectious agents have been implicated in both. Infectious mononucleosis causes a 2-3 fold increased risk of getting multiple sclerosis and is a common trigger for chronic fatigue syndrome. The ME/CFS BDNF study was a very small one, but it did suggest that, just as in multiple sclerosis, neuron repair mechanisms were not up to snuff. Some studies suggest that neuroinflammation – in lower amounts than MS – may be present in ME/CFS. Similar age-related patterns of incidence suggest that hormones, autoimmune processes, and/or viruses may play a role in both.
For the purposes of the compound this blog is about, though, the key factor is the often dramatic reduction in MS symptoms seen during the third trimester of pregnancy – when estrogen levels peak. Dramatic reductions in ME/CFS symptoms occur in some patients during pregnancy as well. (Women with fibromyalgia appear to get worse, not better during pregnancy.) That suggests female hormones play a role in both disorders.
That wouldn’t surprise Gordon Broderick of Dr. Klimas’s Institute for Neuroimmune Studies of Nova Southeastern University. Broderick’s models suggest that estrogen in combination with HPA axis dysregulation may set the stage for ME/CFS in women. The female hormone connection probably wouldn’t surprise Dr. Unger at the CDC either. A CDC study found high rates of gynecological disorders in the CDC’s CFS patients.
The neurons in MS appear to be damaged by inflammatory processes produced by activated T-cells, macrophages, and glial cells. Estrogen has long been known to have neuroprotective effects, and low estrogen levels or signaling could play a role. The fact that ME/CFS incidence spikes in women in adolescence and middle age also suggests hormones do play a role.
Estrogen may be implicated in ME/CFS and MS, but estrogen treatment is not suggested in either disease and has been linked to an increased incidence of breast and uterine cancers.
Estrogen-Affecting Drug Created
In hopes of creating remissions similar to those seen during pregnancy, researchers from UC Riverside and the Rockefeller University in New York began experimenting with a compound called indazole chloride which can stimulate specific estrogen receptors (ER β ) without estrogen being present. This receptor is present in cells found in the peripheral immune system and the central nervous system (neurons, astrocytes, microglia), and the compound is believed to affect immune functioning in both.
The researchers focused on mouse models of experimental autoimmune encephalomyelitis (EAE) that have been developed to help understand brain inflammation and demyelination.
The results, thus far, have been fantastic. The drug has been able not just to reverse symptoms but to actually help rebuild the myelin sheaths surrounding the nerves, and it’s been able to do this long after the damage first occurred. It also increased levels of the nerve repair agent BDNF. It apparently can do all this, not just in mouse models of MS, but in traumatic brain and spinal cord injury. As good as the drug has been thus far, researchers believe they can tweak it to make it more effective.
Perhaps more interestingly with respect to potential neuroinflammatory disorders such as chronic fatigue syndrome, it also inhibits inflammation (microglia activation).
Thus far the drug has only been tested in laboratory animals, but clinical trials are reportedly starting in humans soon. Other very promising drugs have failed to make the leap from animal models to humans, but this drug, which appears to able to both decrease inflammation and effect neuron repair, has a lot going for it.
This potential blockbuster drug hasn’t been tested in humans in multiple sclerosis yet, let alone chronic fatigue syndrome, but its ability to repair damaged nerves and reduce inflammation is more than intriguing.
We should keep in mind that, given the slow, slow, slow pace of drug development in ME/CFS, it’s likely (unless Ampligen is approved) that people with ME/CFS will find help from drugs developed for other disorders long before they will get help from drugs developed specifically for ME/CFS. It’s good to keep an eye out for such possibilities.
Thanks to Carol for passing this study on.