Here’s my pick of this week’s news, as published in Multiple Sclerosis News Today.
The possibility that this discovery may lead to the development of new drugs with fewer side effects is good news.
How the multiple sclerosis (MS) therapy Tecfidera (dimethyl fumarate) works on a molecular level has finally been uncovered, using a new method that can map a drug’s protein targets. The insights gained may open up new avenues for the development of more specific drugs, based on the same mechanisms, but with fewer side effects.
The study, “Chemical proteomic map of dimethyl fumarate–sensitive cysteines in primary human T cells,” was published in the journal Science Signaling.
“This new technology has given us insights into the therapeutic modulation of the immune system that we could not have obtained with standard approaches,” John R. Teijaro, an assistant professor at The Scripps Research Institute (TSRI) and co-senior author of the study, said in a news release.
Although Tecfidera is the most widely prescribed MS drug available as a pill, researchers have not really understood exactly how it works. This is often the case for drugs that have been around for a while, and dimethyl fumarate is also the main component of the psoriasis drug Fumaderm, which has been used successfully since the 90s. (Tecfidera was approved for relapsing MS by the U.S. Food and Drug Administration in 2013).
Not being a scientist, it remains puzzling to me that a drug can be approved and used without knowing HOW it works
Do we want visible proof of treatment? I suppose that it depends how well it works.
Antioxidant-filled nanoparticles injected under the skin may become a future multiple sclerosis treatment that comes with a perk or a drawback, depending on how a patient sees it. The injection leaves a temporary dark spot on the skin, resembling a tattoo.
The tattoo might be a small issue considering that the particles have a huge advantage. They only inactivate immune T-cells — the main cell type driving MS — leaving other immune cells unaffected, potentially reducing side effects.
The proof-of-concept study, “Preferential uptake of antioxidant carbon nanoparticles by T lymphocytes for immunomodulation,” published in the journal Scientific Reports, was a joint effort between researchers at Baylor College of Medicine and Rice University, both in Texas.
“The majority of current treatments are general, broad-spectrum immunosuppressants,” Redwan Huq, lead author of the study and a graduate student at Baylor, said in a news release. “They’re going to affect all of these cells, but patients are exposed to side effects (ranging) from infections to increased chances of developing cancer. So we get excited when we see something new that could potentially enable selectivity.”
Once again, any reduction in side effects is to be welcomed.
Patient safety move gets caught up in red tape of FDA’s rule book.
Active Biotech acknowledged in an update on laquinimod, the oral small molecule being developed by Teva Pharmaceutical Industries to treat multiple sclerosis (MS) and Huntington’s disease (HD), that the U.S. Food and Drug Administration (FDA) has rescinded the special protocol assessment given to a Phase 3 study of the treatment in relapsing MS patients because of a dose change that — necessarily, the company said — was made without prior FDA approval.
Laquinimod, which Active and Teva are working together to develop, is being evaluated for safety, efficacy and tolerability in the CONCERTO study (NCT01707992), a double-blind and placebo-controlled trial that was investigating two oral doses of laquinimod — 0.6 mg/day or 1.2mg/day — in relapsing MS patients. But the Data Monitoring Committee (DMC) supervising this trial and a similar study in progressive MS patients recommended use of higher doses be discontinued immediately in January, after cardiovascular events were reported in eight patients (none fatal) — seven in the relapsing MS and one in the progressive MS studies.
According to an Active Biotech press release, “Teva submitted to the FDA an amendment to the SPA to account for this change [in February]. However, per FDA regulatory process, the SPA [special protocol assessment] was rescinded as all changes must be agreed to prior to implementation of the change. This requirement could not be fulfilled in the current case, since the DMC recommendation triggered an immediate action … in the interest of patient safety.”
Why can’t FDA rules cope with an amendment made in the name of patient safety, during the course of a study? It’s time this regulatory body woke up, embraced flexibility and joined the 21st century.
This development looks as though it may be exciting.
A new study shows that an enzyme called hyaluronidase may be effective in reducing muscle spasticity resulting from neurological disorders such as multiple sclerosis.
The results were published in a study titled “Human Recombinant Hyaluronidase Injections For Upper Limb Muscle Stiffness in Individuals With Cerebral Injury: A Case Series,” in the journal EBioMedicine by a group of researchers from the NYU Langone Medical Center.
Muscle spasticity is a condition characterized by muscle stiffness in one or more muscles and reduced joint movement, which causes pain and disability. Existing treatments include drugs that relax the muscles, such as Botox (botulinum toxin), but these therapies can also cause muscle weakness, making movement more difficult. The necessity for a treatment option that could effectively help patients with their movement problems led the team to consider the possible involvement of a sugar molecule, called hyaluronan. This molecule accumulates in the joints and muscles after neurological damage, promoting stiffness.
The team hypothesized that injections of an enzyme called hyaluronidase, which breaks down hyaluronan, would reverse its accumulation, reduce muscle stiffness, and increase joint movement.
Let’s stay tuned for further news on this – could be good.
New view on myelin degeneration being caused by instability of its own membrane challenges long-held beliefs.
In multiple sclerosis, scientists have long believed that the body’s own immune system attacked myelin sheaths, the “insulating tape” that surrounds neurons, causing the disease. But researchers at Tel Aviv University are challenging that view, in a study reporting that MS may in fact be triggered by an instability inherent in the myelin membranes.
The study, “Structural Transition in Myelin Membrane as Initiator of Multiple Sclerosis,” was published in the Journal of the American Chemical Society (JACS).
“We found that small modifications in the myelin sheaths create structural instabilities that may help the immune system to enter and attack neurons,” Roy Beck, the study’s principal investigator, and a professor at the university’s School of Physics and Astronomy and the Sagol School of Neurosciences, said in a news release. “Current therapeutic approaches have focused on the autoimmune response without identifying a clear mechanism. Our research suggests a new avenue for multiple sclerosis therapies and diagnostics.”
Researchers identified the exact alterations on myelin sheaths that lead to structural instabilities and, subsequently, to autoimmune attacks.
“After years of research, we were amazed to discover that a possible trigger for the outbreak of the disease could be found in the membrane’s physical structure,” said Beck.
Amazing what can still be discovered by determined researchers.
Note: Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Multiple Sclerosis News Today, or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to multiple sclerosis.
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