Nerve cells stripped of their insulation can no longer carry vital information, leading to the numbness, weakness and vision problems often associated with multiple sclerosis. A new study shows an overlooked source may be able to replace that lost insulation and provide a new way to treat diseases like MS.
Cells called neurons make the central nervous system work by passing electrical signals along threadlike connections called axons. Axons do their work best when wrapped in an insulating coating of a fatty substance called myelin.
“When you lose myelin, axons don’t conduct at their normal speed or don’t conduct at all,” says Ian Duncan, a neuroscientist at the University of Wisconsin–Madison’s School of Veterinary Medicine. “And if enough of them are affected — such as in a big area of demyelination in MS — you develop clinical symptoms related to that part of the nervous system.”
Myelin is made by oligodendrocytes, cells that can reach out to several nearby axons to wrap parts of them in the protective myelin sheath.
Consensus has held that once an axon is robbed of its myelin, the only way to bring it back is by starting with fresh oligodendrocytes. Only oligodendrocytes arising from precursors called oligodendrocyte progenitor cells can apply a new coat of myelin to axons, goes the dogma. Thus, MS treatments aimed at remyelination have focused on recruiting progenitor cells in demyelinated areas (called plaques), and spurring them to develop.
However, researchers led by Duncan have shown in a study published today in the Proceedings of the National Academy of Sciences that starting from progenitor cells is not the only route to remyelination. In cats and rhesus macaques experiencing a severe loss of myelin, Duncan found fully developed oligodendrocytes already in place were reaching out and beginning to coat affected axons with myelin once again.
The catch, if there is one, is that to be helpful and remyelinate damaged axons, the adult oligodendrocytes may still need to have connections to surviving myelin segments — called “internodes” — on other axons.
“If this cell is still biologically active and maintaining these internodes, it can re-extend processes out to these demyelinated segments,” says Duncan, whose work is supported by the National Multiple Sclerosis Society. “Those processes can make new myelin sheaths, which end up being thinner and shorter than the previous internodes.”
But even thinner myelin will restore nerve function, as Duncan and colleagues reported in 2009.
Cats fed irradiated food for several months develop severe myelin loss throughout the nervous system. When the cats returned to a regular diet, nerve function was restored because of extensive myelin repair.
The cats’ demyelination problems are unusual as a lab model of the disease.
“The de facto model to study demyelination and remyelination is in a mouse fed a toxin called cuprizone,” Duncan says. “But the toxin kills oligodendrocytes. So, studying the mouse, you naturally wouldn’t see any of the original oligodendrocytes beginning remyelination.”
In the new study, the researchers looked at the cats’ nervous tissue and found a unique myelin mosaic — axons surrounded by thick layers of myelin (formed during development when the axons themselves grew) were interspersed with other axons surrounded by thin layers of myelin.
“The most likely explanation of that mosaic appearance is surviving oligos,” Duncan says. “Thick myelin sheaths are never seen following remyelination, just thin sheaths. And surviving adult oligodendrocytes are adjacent to these sites of demyelination, making them likely candidates for myelin repair.”
Sure enough, the researchers found oligodendrocytes connected to both thick and thin myelin sheaths in the cat spinal cord.
The discovery of the mature myelin-producing cells’ capacity for repair opens new opportunities to slow or reverse the disease.
They also found this association when they reached back to a decades-old monkey model of demyelination. Neuropathologist Dimitri Agamanolis tried to make a model of another human demyelinating disease — called sub-acute combined degeneration and caused by Vitamin B12 deficiency — at Case Western Reserve University in the 1970s. Agamanolis had saved preserved blocks of sampled nervous tissue from the monkeys, and he shared them with Duncan. The monkeys’ myelin lesions resembled those in the cats.
“You see in the monkeys, too, single oligodendrocytes connected to mature myelin sheaths that also have processes extended out to and surrounding demyelinated axons,” Duncan says.
The UW–Madison researchers enlisted Grahame Kidd and the private research lab Renovo Neural in Cleveland to reconstruct stacks of electron microscope images of cat nerve cells into 3D representations that show oligodendrocytes reaching up and down the spinal cord, sustaining mature myelin and remyelinating damaged sheaths.
The process may not be playing out in human MS patients fast enough to help mitigate the progression of the disease, Duncan says. Or too many oligodendrocytes may lose so many of their internodal connections that they become inactive or die.
But the discovery of the mature myelin-producing cells’ capacity for repair opens new opportunities to slow or reverse the disease.
“Right now, the emphasis is on promoting the numbers of oligo progenitors and their differentiation, particularly into adult oligodendrocytes,” says Duncan. “What this work provides is a different target.”
That target will call for new therapeutic approaches — finding drugs, for example, that rally the oligodendrocytes to reach out with new lifelines to damaged myelin sheaths.
“In fighting complex diseases, such as MS, the more tools you have on hand, the better,” Duncan says. “If these adult cells are recruitable in some fashion, we should be looking at ways to do it.”
The Latest on: Multiple sclerosis
via Google News
The Latest on: Multiple sclerosis
- Sonnie Badu’s ‘Lions over Frogs’ T-shirts to raise funds for man with multiple sclerosison April 13, 2021 at 4:43 am
Ghanaian musician based in the United Kingdom, Sonnie Badu, has announced plans of releasing limited ‘Lions over Frogs’ T-shirts to raise funds to foot medical bills of a man diagnosed with multiple ...
- Artificial Intelligence Identifies Novel Multiple Sclerosis Subtypeson April 12, 2021 at 7:44 am
A new study published in Nature Communications used artificial intelligence (AI) to identify 3 new multiple sclerosis (MS) subtypes, which may help identify which individuals are more likely to have ...
- How to Be Your Own Advocate at the Doctor's Office When Diagnosed With Relapsing Multiple Sclerosison April 12, 2021 at 7:10 am
We've partnered with Biogen to give you the information you need to make the most of your doctor's appointments, including by talking about treatments for your specific condition. For U.S. audiences ...
- AI identifies three subtypes of multiple sclerosis in MRI brain scanson April 11, 2021 at 8:23 pm
Scientists may have identified three new subtypes of multiple sclerosis (MS). A team trained artificial intelligence algorithms on a large dataset of MRI scans of the brains of MS patients, and ...
- AI identifies 3 new multiple sclerosis subtypeson April 11, 2021 at 1:00 am
A new analysis of brain MRI scans of people with multiple sclerosis (MS) reveals that individual cases fall into one of three newly discovered MS subtypes.
- Secondary Progressive Multiple Sclerosis Drug Market 2021 Current and Future Trend Scenario Explored In New Latest Research Report By 2027on April 9, 2021 at 12:30 am
The latest report as Secondary Progressive Multiple Sclerosis Drug Market acknowledges Size, Application Segment, Type, Regional Outlook, Market Demand, Latest Trends, and Secondary Progressive ...
- Multiple Sclerosis Treatment Market 2021 : Latest Industry Trends, Growth, Share, Size and 2026 Forecast Research Report with Top countries Dataon April 8, 2021 at 11:19 pm
The MarketWatch News Department was not involved in the creation of this content. Apr 09, 2021 (The Expresswire) -- Global “Multiple Sclerosis Treatment Market" 2021-2026 Research Report provides key ...
- Gene expression profiles of YAP1, TAZ, CRB3, and VDR in familial and sporadic multiple sclerosis among an Iranian populationon April 8, 2021 at 3:43 pm
Blood samples were obtained from patients referred to the MS clinic of Kashani Hospital, affiliated with Isfahan University of Medical Sciences between June 2018 and September 2019, and were collected ...
- Epidemiology, treatment patterns and healthcare utilizations in multiple sclerosis in Taiwanon April 8, 2021 at 10:44 am
Real-world” data on the nationwide epidemiology and treatment patterns of multiple sclerosis (MS) is very scarce in Asia. This study is aim to evaluate the 10-years trends in epidemiology and ...
via Bing News