Archive for the ‘multiple sclerosis’ Category

A single genetic mutation may increase a person’s risk of developing a rare, severe form of multiple sclerosis (MS) by roughly 60 percent, according to a study published recently in the journal Neuron.

That’s an unusually straightforward result for a complex disease like MS, which has previously been traced to hundreds of mutations that each increases the risk of developing the disease only slightly.

“That’s why our finding is unprecedented,” Carles Vilariño-Güell, Ph.D., an assistant professor of medical genetics at The University of British Columbia and one of the paper’s senior authors, told Healthline.

His team found the mutation by combing through a database of Canadians with MS who had donated blood samples as part of the Canadian Collaborative Project on Genetic Susceptibility to MS.

Some of these samples belonged to a family that was disproportionately diagnosed with the disease. Four first cousins and two parents developed MS.

The team isolated a common mutation from their DNA, and looked for that mutation in other individuals in the database.

That’s how they found a second family similarly afflicted. Three first cousins and two parents were diagnosed with MS.

Having so many cases of MS within a family is rare. The disease is not considered truly heritable, although a person’s risk does increase if a parent or sibling has the disease.

The families shared another rare trait. Most had the more severe version of the disease known as primary progressive MS, which makes up 10 to 15 percent of all MS cases.

Treatments for primary progressive MS have so far eluded scientists, although there are promising clinical trials underway of a drug called Ocrelizumab.


Future Research

The study found the mutation only in a handful of people, all of whom were diagnosed with a rare form of the disease.

Therefore, the researchers don’t suggest they have found the genetic basis of MS.

But they do think they’ve discovered a way to study how the disease progresses in the body and what drugs could be developed to slow or even stop it

Bruce Bebo, Ph.D., vice president of research at the National Multiple Sclerosis Society, agrees.

“Studying the genetics of a very rare form that is inherited can give us clues about pathways involved in MS in the general population,” he told Healthline.

The mutation appears to disable a regulatory gene called NR1H3, which codes for a protein that helps regulate the inflammation and the metabolism of lipids.

The researchers now plan to engineer a similar mutation in mice so they can study the outcome of a disabled NR1H3 gene and test potential new drugs in an animal model.

And because the NR1H3 pathway has already been implicated in diseases like atherosclerosis and heart disease, there are already drugs in clinical trials for safety that could be repurposed for treating MS, Vilariño-Güell said.

“Understanding the genetics of MS could help us get closer to individualizing therapy to people for better outcomes,” Bebo said.

Getting Personal with Treatment

People with a disease like MS, which appears in so many different ways and can be linked to so many different genetic components, could benefit by personalized medicine.

If the mechanism of each disease causing mutation or group of mutations is pinpointed, scientists could potentially design more effective, targeted treatments rather than the standard one-size-fits-all therapies.

That means tracking down the many different genetic hotspots that are linked to MS.

Overall, genetic predisposition accounts for only about a third of a person’s risk of developing the disease, Bebo said. Within that category only about half the genes responsible can be identified.

Researchers don’t know where the other half of that genetic risk comes from, Bebo said, but it makes sense that it would include rare mutations like this one that help explain risk in a small fraction of MS patients.

And there could be many different versions of these mutations.

“Odds are if you look at a different family the genetic risk would probably be something different than this,” Bebo said.

Speeding Through the Genome

The Canadian database has been available since the late 1990s, but only recently has the team had access to exome sequencing, a powerful, efficient tool that makes searching for tiny genetic changes easier.

This technique sequences only the DNA that codes for proteins — leaving the other 98 percent behind. It’s like speed reading the genome.

Exome sequencing has been particularly helpful for finding so-called “Mendelian” diseases — diseases that can be traced to a single, heritable mutation just like Gregor Mendel’s purple and white pea flowers. Cystic fibrosis and sickle cell anemia are two examples of these diseases.

With this discovery, the researchers say that have found a Mendelian form of MS.

That doesn’t mean the discovery won’t be beneficial for the 85 percent of people diagnosed with relapsing remitting MS. In many of those patients, the disease eventually changes course and becomes progressive.

Whatever is learned about primary progressive MS — a condition that doesn’t respond to treatments for other types of MS — could also potentially help those with secondary progressive MS, the researchers say.

http://www.healthline.com/health-news/form-of-ms-could-be-caused-by-single-genetic-mutation#5


Holly Drewry, 25, of Sheffield, was wheelchair bound after the birth of her daughter Isla, now two.

A pioneering new stem cell treatment is reversing and then halting the potentially crippling effects of multiple sclerosis.

Patients embarking on a ground-breaking trial of the new treatment have found they can walk again and that the disease even appears to be stopped in its tracks.

Holly Drewry, 25, from Sheffield, was wheelchair bound after the birth of her daughter Isla, now two. But Miss Drewry claims the new treatment has transformed her life.

She told the BBC’s Panorama programme: “I couldn’t walk steadily. I couldn’t trust myself holding her (Isla) in case I fell. Being a new mum I wanted to do it all properly but my MS was stopping me from doing it.

“It is scary because you think, when is it going to end?”

The treatment is being carried out at Royal Hallamshire Hospital in Sheffield and Kings College Hospital, London and involves use a high dose of chemotherapy to knock out the immune system before rebuilding it with stem cells taken from the patient’s own blood.

Miss Drewry had the treatment in Sheffield. She said: “I started seeing changes within days of the stem cells being put in.

“I walked out of the hospital. I walked into my house and hugged Isla. I cried and cried. It was a bit overwhelming. It was a miracle.”

Her treatment has now been reviewed and her condition found to have been dramatically halted. She will need to be monitored for years but the hope is that her transplant will be a permanent fix.

She is now planning to get married.

For other patients, the results have been equally dramatic. Steven Storey was a marathon runner and triathlete before he was struck down with the disease and left completely paralysed: “I couldn’t flicker a muscle,” he said.

But within nine days of the treatment he could move his toe and after 10 months managed a mile-long swim in the Lake District. He has also managed to ride a bike and walk again.

“It was great. I felt I was back,” he said.

Mr Storey celebrated his first transplant birthday with his daughters. His treatment has been reviewed and, like Miss Drewry, there was no evidence of active disease.

The treatment – which effectively ‘reboots’ the immune systems – is the first to reverse the symptoms of MS, which has no cure, and affects around 100,000 people in Britain.

Stem cells are so effective because they can become any cell in the body based on their environment.

Although it is unclear what causes MS, some doctors believe that it is the immune system itself which attacks the brain and spinal cord, leading to inflammation and pain, disability and in severe cases, death.

Professor Basil Sharrack, a consultant neurologist at Sheffield Teaching Hospitals NHS Foundation Trust, said: “Since we started treating patients three years ago, some of the results we have seen have been miraculous.

“This is not a word I would use lightly, but we have seen profound neurological improvements.”

During the treatment, the patient’s stem cells are harvested and stored. Then doctors use aggressive drugs which are usually given to cancer patients to completely destroy the immune system.

The harvested stem cells are then infused back into the body where they start to grow new red and white blood cells within just two weeks.

Within a month the immune system is back up and running fully and that is when patients begin to notice that they are recovering.

However specialists warn that patients need to be fit to benefit from the new treatment.

The research has been published in the Journal of the American Medical Association.

http://www.telegraph.co.uk/news/health/news/12104774/Miraculous-results-from-new-MS-treatment.html

Thanks to Steve Weihing for bringing this to the It’s Interesting community.

brain

The many documented cases of strange delusions and neurological syndromes can offer a window into how bizarre the brain can be.

It may seem that hallucinations are random images that appear to some individuals, or that delusions are thoughts that arise without purpose. However, in some cases, a specific brain pathway may create a particular image or delusion, and different people may experience the same hallucination.

In recent decades, with advances in brain science, researchers have started to unravel the causes of some of these conditions, while others have remained a mystery.

Here is a look at seven odd hallucinations, which show that anything is possible when the brain takes a break from reality.

1. Alice-in-Wonderland syndrome
This neurological syndrome is characterized by bizarre, distorted perceptions of time and space, similar to what Alice experienced in Lewis Carroll’s “Alice’s Adventures in Wonderland.”

Patients with Alice-in-Wonderland syndrome describe seeing objects or parts of their bodies as smaller or bigger than their actual sizes, or in an altered shape. These individuals may also perceive time differently.

The rare syndrome seems to be caused by some viral infections, epilepsy, migraine headaches and brain tumors. Studies have also suggested that abnormal activity in parts of the visual cortex that handle information about the shape and size of objects might cause the hallucinations.

It’s also been suggested that Carroll himself experienced the condition during migraine headaches and used them as inspiration for writing the tale of Alice’s strange dream.

English psychiatrist John Todd first described the condition in an article published in the Canadian Medical Association Journal in 1955, and that’s why the condition is also called Todd’s syndrome. However, an earlier reference to the condition appears in a 1952 article by American neurologist Caro Lippman. The doctor describes a patient who reported feeling short and wide as she walked, and referenced “Alice’s Adventures in Wonderland” to explain her body image illusions.

2. Walking Corpse Syndrome
This delusion, also called Cotard’s Syndrome, is a rare mental illness in which patients believe they are dead, are dying or have lost their internal organs.

French neurologist Jules Cotard first described the condition in 1880, finding it in a woman who had depression and also symptoms of psychosis. The patient believed she didn’t have a brain or intestines, and didn’t need to eat. She died of starvation.

Other cases of Cotard’s syndrome have been reported in people with a range of psychiatric and neurological problems, including schizophrenia, traumatic brain injury and multiple sclerosis.

In a recent case report of Cotard’s syndrome, researchers described a previously healthy 73-year-old woman who went to the emergency room insisting that she was “going to die and going to hell.” Eventually, doctors found the patient had bleeding in her brain due to a stroke. After she received treatment in the hospital, her delusion resolved within a week, according to the report published in January 2014 in the journal of Neuropsychiatry.

3. Charles Bonnet syndrome
People who have lost their sight may develop Charles Bonnet syndrome, which involves having vivid, complex visual hallucinations of things that aren’t really there.

People with this syndrome usually hallucinate people’s faces, cartoons, colored patterns and objects. It is thought the condition occurs because the brain’s visual system is no longer receiving visual information from the eye or part of the retina, and begins making up its own images.

Charles Bonnet syndrome occurs in between 10 and 40% of older adults who have significant vision loss, according to studies.

4. Clinical lycanthropy
In this extremely rare psychiatric condition, patients believe they are turning into wolves or other animals. They may perceive their own bodies differently, and insist they are growing the fur, sharp teeth and claws of a wolf.

Cases have also been reported of people with delusional beliefs about turning into dogs, pigs, frogs and snakes.

The condition usually occurs in combination with another disorder, such as schizophrenia, bipolar disorder or severe depression, according to a review study published in the March issue of the journal History of Psychiatry in 2014.

5. Capgras delusion
Patients with Capgras delusion believe that an imposter has replaced a person they feel close to, such as a friend or spouse. The delusion has been reported in patients with schizophrenia, Alzheimer’s disease, advanced Parkinson’s disease, dementia and brain lesions.

One brain imaging study suggested the condition may involve reduced neural activity in the brain system that processes information about faces and emotional responses.

6. Othello syndrome
Named after Shakespeare’s character, Othello syndrome involves a paranoid belief that the sufferer’s partner is cheating. People with this condition experience strong obsessive thoughts and may show aggression and violence.

In one recent case report, doctors described a 46-year-old married man in the African country Burkina Faso who had a stroke, which left him unable to communicate and paralyzed in half of his body. The patient gradually recovered from his paralysis and speaking problems, but developed a persistent delusional jealousy and aggression toward his wife, accusing her of cheating with an unidentified man.

7. Ekbom’s syndrome
Patients with Ekbom’s syndrome, also known as delusional parasitosis or delusional infestations, strongly believe they are infested with parasites that are crawling under their skin. Patients report sensations of itching and being bitten, and sometimes, in an effort to get rid of the pathogens, they may hurt themselves, which can result in wounds and actual infections.

It’s unknown what causes these delusions, but studies have linked the condition with structural changes in the brain, and some patients have improved when treated with antipsychotic medications.

http://www.livescience.com/46477-oddest-hallucinations.html

Researchers at the Karolinska Institute, Sweden, say guidelines that advise people to stay out of the sun unless wearing sunscreen may be harmful, particularly in northern countries which have long, cold winters.

Exposure to ultraviolet radiation from sunlight is often cited as a cause of skin melanoma (malignant tumour of melanocytes) and avoiding overexposure to the sun to prevent all types of skin cancer is recommended by health authorities.

But the new study, which followed nearly 30000 women over 20 years, suggests that women who stay out of the sun are at increased risk of melanomas and are twice as likely to die from any cause, including cancer.

It is thought that a lack of vitamin D may be to blame. Vitamin D is created in the body through exposure to sunshine and a deficiency is known to increase the risk of diabetes, TB, multiple sclerosis and rickets.

Previous studies showed that vitamin D can increase survival rates for women with breast cancer while deficiencies can signal prostate cancer in men.

The study looked at 29518 Swedish women who were recruited from 1990 to 1992 and asked to monitor their sunbathing habits.

After 20 years there had been 2545 deaths and it was found that women who never sunbathed were twice as likely to have died from any cause.

Women who sunbathed in the mild Swedish summer were also 10% less likely to die from skin cancer, although those who sunbathed abroad in sunnier countries were twice as likely to die from melanoma.

Yinka Ebo, senior health information officer at Cancer Research UK, said striking a balance was important.

“The reasons behind higher death rates in women with lower sun exposure are unexplained . overexposure to UV radiation from the sun or sunbeds is the main cause of skin cancer.”

http://www.timeslive.co.za/thetimes/2014/05/09/avoiding-sunshine-could-kill-you-study-finds

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

benzotropine

A drug that treats Parkinson’s disease might also work against multiple sclerosis, or MS.

In MS patients, an aberrant immune onslaught degrades the fatty myelin sheaths that coat nerve fibers, causing blurred vision, weakness, loss of coordination and other symptoms.

Luke Lairson of the Scripps Research Institute in La Jolla, Calif., and colleagues tested a host of compounds to see which might boost regeneration of oligodendrocytes, the brain cells that make myelin and which are often lacking in MS. Using the cells’ forerunners, nascent brain cells called oligodendrocyte precursor cells, from rats and mice, the researchers found that benztropine proved adept at steering these cells to become myelin-making oligodendrocytes.

The researchers then induced in mice a disease that mimics MS and gave some of the animals benztropine, others a standard MS drug (fingolimod or interferon beta) and some no drug at all. Whether given before or after disease onset, benztropine reduced symptom severity and prevented relapses better than other MS drugs. Mice getting no drug fared the poorest, according to results appearing October 9 in Nature.

A cell count of brain tissue revealed that mice getting benztropine had substantially more mature oligodendrocytes than mice getting no drug. Further analyses suggested the animals’ symptom improvement with benztropine resulted from a rebuilding of the myelin sheaths, not from suppressing the animals’ immune systems. The researchers think the drug, if approved for use in MS, might work in concert with immune-suppressing drugs.

https://www.sciencenews.org/article/old-drug-may-have-new-trick