Can MS Patients Anticipate An End To Injections?
Recently reported two-year data from the completed CLARITY study shows that compared to placebo, oral Cladribine tablets significantly cut the rate of clinical relapses, disability progression, and brain lesions in those with RRMS, supporting preliminary data reported in January this year. Over two years, 80 percent of the patients receiving low-dose oral Cladribine and 79 percent of those in the high-dose group experienced no clinical relapse, compared to 61 percent of those on placebo. Cladribine treatment was also shown to cut the risk of disability progression by more than 30 percent. Cladribine can interfere with the activity of white blood cells which are essential for a properly functioning immune system and underlie the immune attacks that cause the unpredictable symptoms of MS. Careful scrutiny is being taken to monitor Cladribine’s safety profile.
While the phase III CLARITY study has already been completed, there are three clinical trials that continue to evaluate this promising new treatment. One study is looking at the effectiveness of Cladribine given as an add-on therapy with interferon-beta. Another study is designed to evaluate the effectiveness of the drug in people who have had a first demyelinating event and are at risk for developing MS. The third study is an extension of the original CLARITY study and is looking at the long-term safety of Cladribine over four years.
Oral Cladribine has been designated by the FDA as a “Fast Track Product,” which should expedite its future review. If results hold steady, within the next couple of years we can all look forward to an exciting new treatment that may be the first oral therapy to slow the progression of MS.
For more information about the on-going Cladribine studies go to “Research News” under the Research tab
Imagine this: a new therapy works to protect brain cells from the damage caused by MS and possibly even repairs them. But there’s no way to tell when it is actually working.
Nearly 60 scientists discussed the problem at a workshop held last summer in Amsterdam by the National MS Society’s International Advisory Committee on Clinical Trials. Findings were published in Nature Reviews Neurology 5, 256-266, and is available free at nature.com/nrneurol/journal/v5/n5/pdf/nrneurol.2009.41.pdf.
The scientists assessed emerging and current imaging technologies, rating qualities such as how well results corresponded to clinical symptoms. Three technologies stood out:
- Optical coherence tomography (OCT) uses infrared light to measure the thickness of the nerve fiber layer of the retina at the back of the eye.
- Magnetic transfer ratio (MTR) measures how much energy is transferred or absorbed by protons in the brain.
- Whole brain volume measurement, which is done with a series of MRIs, has excellent sensitivity to disease changes, researchers noted, but does not distinguish well between types of tissue damage.
The researchers concluded that a combination of these technologies appears to be best to determine if a new therapy is working to protect brain cells. But they also agreed that it is much harder to detect whether a therapy is working to repair brain cells. You may hear about fMRI, an imaging technology that measures the amount of oxygen used by different areas of the brain, as a way to detect repair as scientists conduct more studies.
Breastfeeding may benefit women with MS, a recent study suggests. In the study, only 36% of women with MS who breastfed exclusively for at least two months after birth experienced an exacerbation, as compared to 87% who did not breastfeed or who supplemented with formula.
While the study was small, the results question the benefit of forgoing breastfeeding in order to resume MS treatment after birth. The study was published online in the Archives of Neurology in June 2009.
Not breastfeeding reactivates the ovaries, said lead researcher Dr. Annette Langer-Gould, a process that may be the reason MS exacerbations typically increase after birth.
The researchers will be conducting a larger study to confirm the findings and possibly identify the immunosuppressive factor in breastfeeding.
A team funded in part by the National MS Society’s Promise: 2010 Campaign has demonstrated that the “Wnt signaling pathway” – a complex network of proteins that interact during brain development – may also play an important role in the failure of nerve-protecting myelin to repair itself in people with MS.
In the brain and spinal cord, myelin is made and maintained by cells known as oligodendrocytes, which are also damaged in MS. Oligodendrocytes develop from precursor “stem” cells; for unknown reasons, these cells often fail to maintain their capacity for myelin repair in people with MS. One goal of MS research is to find ways to stimulate these precursors to make new oligodendrocytes that will repair the damaged myelin.
High-tech screens were conducted to detect the activity of genes, called transcription factors, that control other genes. 1,040 transcription factor genes within the nervous systems of mice were screened that were at key stages of recovery from myelin damage, trying to detect which genes were active during stages of myelin repair. The screen pointed to over 50 genes, of which the gene for a factor called “Tcf4” stood out, because it was most active in damaged areas where repair attempts were under way. Tcf4 is involved in the Wnt signaling pathway.
Up to now the Wnt pathway was known to be important in the early development of the brain and other tissues, but was not previously linked to myelin repair.
An elaborate series of experiments to further understand how Wnt signals might affect myelin repair were conducted. Among the findings, it was demonstrated that causing the Wnt signals to be overly active in mice delayed myelin repair significantly. Tissue samples from people with MS were also examined, and found that Tcf4 was active only in areas damaged by MS, not in healthy tissue.
This is the first study that links the Wnt pathway with disrupted myelin repair in people with MS, and the discovery may offer inroads to finding ways to stimulate stalled myelin repair. Further study, which is ongoing, is needed to understand the interactions necessary for myelin repair and how they might be malfunctioning in MS. Other genes are being looked at that maybe found to be active during myelin repair, in hopes of identifying specific targets for the development of therapies to reverse the damage caused by MS.
In addition to National MS Society support, this study also received funding from the MS Society of the United Kingdom and Northern Ireland, the National Institutes of Health and the Howard Hughes Medical Institute.
A clinical trial of CDP323, an oral compound with a similar mechanism of action as the infused therapy Tysabri® was discontinued when an interim analysis of results showed that participants did not benefit as expected compared with placebo. The drug was being tested in 279 people with relapsing forms of MS recruited worldwide.
CDP323 is an orally taken “alpha-4 integrin antagonist” that was designed to hamper movement of potentially damaging immune cells from the bloodstream, across the “blood-brain barrier” into the brain and spinal cord. Because this drug has a mechanism of action that is similar to Tysabri’s, the release added that no cases of progressive multifocal leukoencephalopathy (PML, a viral infection of the brain that usually leads to death or severe disability) occurred during the study.