Study suggests feasibility of treating encephalopathy with gene therapy

A new study has highlighted that it is feasible to use gene therapy for treating chronic traumatic encephalopathy ( CTE) which is a progressive neurodegenerative disorder.

Researchers demonstrated the effectiveness of the direct delivery of gene therapy by delivering it into the brain of a mouse.

CTE is much more prevalent than was initially realised, and there is currently no therapy available. This new work is potentially ground-breaking as a means to remove the offending Tau phoshoprotein, said the lead researcher.

The disease which is caused by recurrent trauma in the central nervous system, such as those suffered by soldiers, atheletes in contact sports and in accidents, is currently incurable.

Inflammation results in the accumulation of hyperphosphorylated forms of Tau protein (pTau). 

Researchers developed an adeno-associated virus (AAV) vector to deliver an anti-p-Tau antibody to the CNS. They showed that direct delivery of the AAVrh,10anti-p_tau directly into the hippocampus of brain-injured mice was associated with a significant reduction in p-Tau levels across the CNS.

They propose that doses could be scaled up and this strategy could be effective in humans as well.

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Avoid fatty food as it may interrupt communication between gut and body

You may be one of those people who love a cheat meal once in a while that is loaded with butter or oil, or you may be one of those who do not love it but do not mind it either. While there is no denying that food cooked in a lot of oil is very rich in flavour and texture, it does come with its own cost of adverse health effects. Eating excess oily food regularly can cause obesity and increase the risk of cardiovascular problems as well.

A recent study, however, has also linked excess oil and grease in food to the gut's health. According to the study, such food can reduce the communication between the intestine and the rest of your body. The researches found that a high-fat meal can completely shut down the communication for a few hours.

Researchers looked at the enteroendocrine cells, which though occur sparsely in the lining of the gut, play a key role in signally the body about the alimentary canal. These cells are also responsible for the production of certain hormones and have a direct connection with the central nervous system and the brain.

A break in communication between the cells in the gut can lead to problems like insulin sensitivity, indigestion, poor gastrointestinal health, among other health effects.

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Multiple sclerosis: Skin cells may help to repair nerve damage

A personalized treatment for multiple sclerosis may be one step closer, thanks to a new study that reveals how a person's own skin cells could be used to repair the nerve damage that the disease causes.

Led by scientists in the United Kingdom, the study took skin cells from adult mice with multiple sclerosis (MS) and then reprogramed them into neural stem cells (NSCs).

These "induced neural stem cells" (iNSCs) were transplanted into the rodents' cerebrospinal fluid.

There, they reduced inflammation and repaired damage to the central nervous system (CNS).

Lead study author and his team believe that their strategy could offer a promising treatment for MS and other neurological diseases.

MS is a progressive neurological disease that is estimated to affect more than 2.3 million people across the globe.

While the precise causes of MS remain unclear, "an abnormal immune system response" is thought to be involved. Such a response leads to inflammation in the CNS, which causes the destruction of myelin, or the fatty substance that protects nerve fibers.

As a result, the nerve fibers become damaged. This disrupts neuronal signaling and triggers the neurological symptoms of MS, including tingling in the face or extremities and problems with movement, balance, and coordination.

Using stem cells to treat MS
Previous research has investigated the use of NSCs for the treatment of MS. NSCs are stem cells that have the ability to transform into different types of cell in the CNS — including neurons and glial cells.

However, there are some barriers to this strategy. As researchers note, NSCs are derived from embryos, and it would be hard to obtain them in high enough quantities to sustain clinical treatment.
It is also possible that the immune system would see embryo-derived NSCs as foreign invaders and try to destroy them.

As such, researchers have turned their attention toward iNSCs, or NSCs that can be developed by reprogramming adult skin cells. Importantly, since these cells would be derived from the patients themselves, the risk of an immune system attack would be significantly reduced.

To test whether iNSCs could be a feasible treatment option for MS, the researchers tested them on adult mice that had been genetically engineered to develop the condition.

The team took cells from the skin of the mice and reprogramed them into NSCs, effectively making iNSCs. Next, the team transplanted these iNSCs into the cerebrospinal fluid of the mice.
Study yields promising findings

The researchers found that this led to a reduction in levels of succinate, which is a metabolite that the team found is increased in MS. This increase prompts microglia — a type of glial cell found in the CNS — to trigger inflammation and cause nerve damage.

By reducing succinate levels, the iNSCs reprogrammed the microglia — which, in turn, reduced inflammation and brain and spinal cord damage in the mice.

Of course, human clinical trials are needed before iNSCs can be considered as a suitable treatment for MS, but this latest study certainly shows promise.

"Our mouse study suggests that using a patient's reprogrammed cells could provide a route to personalized treatment of chronic inflammatory diseases, including progressive forms of MS."   said the lead author.

"This is particularly promising," Dr.  adds, "as these cells should be more readily obtainable than conventional neural stem cells and would not carry the risk of an adverse immune response."

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Multiple sclerosis: What you need to know

Multiple sclerosis is a chronic disease that affects the central nervous system, especially the brain, spinal cord, and optic nerves. This can lead to a wide range of symptoms throughout the body.

It is not possible to predict how multiple sclerosis (MS) will progress in any individual.

Some people have mild symptoms, such as blurred vision and numbness and tingling in the limbs. In severe cases, a person may experience paralysis, vision loss, and mobility problems. However, this is rare.

It is difficult to know precisely how many people have MS. According to the National Institute for Neurological Disorders and Stroke (NINDS), 250,000–350,000 people in the United States are living with MS.

The National Multiple Sclerosis Society estimate the number could be closer to 1 million.

However, new treatments are proving effective at slowing the disease.
What is MS?
Scientists do not know exactly what causes MS, but they believe it is an autoimmune disorder that affects the central nervous system (CNS). When a person has an autoimmune disease, the immune system attacks healthy tissue, just as it might attack a virus or bacteria.

In the case of MS, the immune system attacks the myelin sheath that surrounds and protects the nerve fibers, causing inflammation. Myelin also helps the nerves conduct electrical signals quickly and efficiently.

Multiple sclerosis means "scar tissue in multiple areas."

When the myelin sheath disappears or sustains damage in multiple areas, it leaves a scar, or sclerosis. Doctors also call these areas plaques or lesions. They mainly affect:

    the brain stem
    the cerebellum, which coordinates movement and controls balance
    the spinal cord
    the optic nerves
    white matter in some regions of the brain

As more lesions develop, nerve fibers can break or become damaged. As a result, the electrical impulses from the brain do not flow smoothly to the target nerve. This means that the body cannot carry out certain functions.
Types of MS

There are four types of MS:

Clinically isolated syndrome (CIS): This is a single, first episode, with symptoms lasting at least 24 hours. If another episode occurs at a later date, a doctor will diagnose relapse-remitting MS.

Relapse-remitting MS (RRMS): This is the most common form, affecting around 85% of people with MS. RRMS involves episodes of new or increasing symptoms, followed by periods of remission, during which symptoms go away partially or totally.

Primary progressive MS (PPMS): Symptoms worsen progressively, without early relapses or remissions. Some people may experience times of stability and periods when symptoms worsen and then get better. Around 15% of people with MS have PPMS.

Secondary progressive MS (SPMS): At first, people will experience episodes of relapse and remission, but then the disease will start to progress steadily.

Find out more here about the different types of MS and what they mean.
Symptoms
Because MS affects the CNS, which controls all the actions in the body, symptoms can affect any part of the body.

The most common symptoms of MS are:

Muscle weakness: People may develop weak muscles due to lack of use or stimulation due to nerve damage.

Numbness and tingling: A pins and needles-type sensation is one of the earliest symptoms of MS that can affect the face, body, or arms and legs.

Lhermitte's sign: A person may experience a sensation like an electric shock when they move their neck, known as Lhermitte's sign.

Bladder problems: A person may have difficulty emptying their bladder or need to urinate frequently or suddenly (urge incontinence). Loss of bladder control is an early sign of MS.

Bowel problems: Constipation can cause fecal impaction, which can lead to bowel incontinence.

Fatigue: This can undermine a person's ability to function at work or at home. Fatigue is one of the most common symptoms of MS.

Dizziness and vertigo: These are common problems, along with balance and coordination issues.

Sexual dysfunction: Both males and females may lose interest in sex.

Spasticity and muscle spasms: This is an early sign of MS. Damaged nerve fibers in the spinal cord and brain can cause painful muscle spasms, particularly in the legs.

Tremor: Some people with MS may experience involuntary quivering movements.

Vision problems: Some people may experience double or blurred vision, a partial or total loss of vision, or red-green color distortion. This usually affects one eye at a time. Inflammation of the optic nerve can result in pain when the eye moves. Vision problems are an early sign of MS.

Gait and mobility changes: MS can change the way people walk, because of muscle weakness and problems with balance, dizziness, and fatigue.

Emotional changes and depression: Demyelination and nerve-fiber damage in the brain can trigger emotional changes.

Learning and memory problems: These can make it difficult to concentrate, plan, learn, prioritize, and multitask.

Pain: Pain is a common symptom in MS. Neuropathic pain is directly due to MS. Other types of pain occur because of weakness or stiffness of muscles.

Less common symptoms include:

    headache
    hearing loss
    itching
    respiratory or breathing problems
    seizures
    speech disorders
    swallowing problems

There is also a higher risk of:

    urinary tract infections
    reduced activity and loss of mobility

These can impact a person's work and social life.

In the later stages, people may experience changes in perception and thinking and sensitivity to heat.

MS affects individuals differently. For some, it starts with a subtle sensation, and their symptoms do not progress for months or years. Sometimes, symptoms worsen rapidly, within weeks or months.

A few people will only have mild symptoms, and others will experience significant changes that lead to disability. However, most people will experience times when symptoms worsen and then get better.

Lhermitte's sign is a common symptom of MS that happens when a person moves their head. Find out more here.
Causes and risk factors

Scientists do not really know what causes MS, but risk factors include:

Age: Most people receive a diagnosis between the ages of 20 and 40 years.

Sex: Most forms of MS are twice as likely to affect women than men.

Genetic factors: Susceptibility may pass down in the genes, but scientists believe an environmental trigger is also necessary for MS to develop, even in people with specific genetic features.

Smoking: People who smoke appear to be more likely to develop MS. They tend to have more lesions and brain shrinkage than non-smokers.

Infections: Exposure to viruses, such as Epstein-Barr virus (EBV), or mononucleosis, may increase a person's risk of developing MS, but research has not shown a definite link. Other viruses that may play a role include human herpes virus type 6 (HHV6) and mycoplasma pneumonia.

Vitamin D deficiency: MS is more common among people who have less exposure to bright sunlight, which is necessary for the body to create vitamin D. Some experts think that low levels of vitamin D may affect the way the immune system works.

Vitamin B12 deficiency: The body uses vitamin B when it produces myelin. A lack of this vitamin may increase the risk of neurological diseases, such as MS.

Previous theories have included exposure to canine distemper, physical trauma, or aspartame, an artificial sweetener, but there is no evidence to support these

There is probably no single trigger for MS, but multiple factors may contribute.

How does MS affect women? Click here to find out more.
Diagnosis

The doctor will carry out a physical and neurological examination, ask about symptoms, and consider the person's medical history.

No single test can confirm a diagnosis, so a doctor will use several strategies when deciding whether a person meets the criteria for a diagnosis.

These include:

    MRI scans of the brain and spinal cord, which may reveal lesions
    spinal fluid analysis, which may identify antibodies that suggest a previous infection
    an evoked potential test, which measures electrical activity in response to stimuli

Other conditions have symptoms that are similar to those of MS, so a doctor may suggest other tests to assess for other possible causes.

If the doctor diagnoses MS, they will need to identify what type it is and whether it is active or not. The person may need more tests in the future to assess for further changes.

Learn more here about the tests for diagnosing MS.
Treatment
There is no cure for MS, but treatment is available that can:

    slow the progression and reduce the number and severity of relapses
    relieve symptoms

Some people also use complementary and alternative therapies, but research does not always confirm the usefulness of these.
Medications to slow progression

Several disease-modifying therapies (DMTs) have approval from the Food and Drug Administration (FDA) for the relapsing forms of MS. These work by changing the way the immune system functions.

A doctor may give some of these by mouth, some by injection, and some as an infusion. How often the person needs to take them and whether or not they can do this at home will depend on the drug.

The following DMTs currently have approval:

Injectable medications

    interferon beta 1-a (Avonex and Rebif)
    interferon beta-1b (Betaseron and Extavia)
    glatiramer acetate: (Copaxone and Glatopa)
    peginterferon beta-1a) (Plegridy)

Oral medications

    teriflunomide (Aubagio)
    fingolimod (Gilenya)
    dimethyl fumarate (Tecfidera)
    mavenclad (cladribine)
    mayzent (siponimod)

Infused medications

    alemtuzumab (Lemtrada)
    mitoxantrone (Novantrone)
    ocrelizumab (Ocrevus)
    natalizumab (Tysabri)

Current guidelines recommend using these drugs from the early stages, as there is a good chance that they can slow the progression of MS, especially if the person takes them when symptoms are not yet severe.

Some drugs are more useful at specific stages. For example, a doctor may prescribe mitoxantrone at a later, more severe stage of MS.

A doctor will monitor how well a drug is working, as there may be adverse effects, and the same drugs do not suit everyone. New drug options coming onto the market are proving to be safer and more effective than some existing ones.

Adverse effects of immunosuppressant drugs include a higher risk of infections. Some medications may also harm the liver.

If a person notices adverse effects or if their symptoms get worse, they should seek medical advice.
Medications for relieving symptoms during a flare

Other drugs are useful when a person experiences a worsening of symptoms, during a flare. They will not need these drugs all the time.

Corticosteroids: These reduce inflammation and suppress the immune system. They can treat an acute flare-up of symptoms in certain types of MS. Examples include Solu-Medrol (methylprednisolone) and Deltasone (prednisone). Steroids can have adverse effects if a person uses them too often, and they are not likely to provide any long-term benefit.

Behavioral changes: If vision problems occur, a doctor may recommend resting the eyes from time to time or limiting screen time. A person with MS may need to learn to rest when fatigue sets in and to pace themselves so they can complete activities.

Problems with mobility and balance: Physical therapy and walking devices, such as a cane, may help. The drug dalfampridine (Ampyra) may also prove useful.

Tremor: A person may use assistive devices or attach weights to the limbs to reduce shaking. Medications may also help with tremors.

Fatigue: Getting enough rest and avoiding heat can help. Physical and occupational therapy can help teach people more comfortable ways to do things. Assistive devices, such as a mobility scooter, can help conserve energy. Medication or counseling may help boost energy by improving sleep.

Pain: A doctor may prescribe anticonvulsant or antispasmodic drugs or alcohol injections to relieve trigeminal neuralgia, a sharp pain that affects the face. Pain relief medication, such as gabapentin, may help with body pain. There are also medications to relieve muscle pain and cramping in MS.

Bladder and bowel problems: Some medications and dietary changes can help resolve these.

Depression: A doctor may prescribe a selective serotonin reuptake inhibitor (SSRI), as these are less likely to cause fatigue than other antidepressant drugs.

Cognitive changes: Donepezil, a drug for Alzheimer's, may help some people.

Learn more here about how to manage an exacerbation of MS.
Complementary and alternative therapies

The following may help with different aspects of MS:

    heat and massage treatment for pain
    acupuncture for pain and gait
    stress management to boost mood
    exercise to maintain strength and flexibility, reduce stiffness, and boost mood
    a healthful diet with plenty of fresh fruits, vegetables, and fiber
    quitting or avoiding smoking

Various supplements are available for purchase online, including vitamin D and Omega-3 supplements.

Some people use these, although scientists have not proven that they will help. A person should not use supplements without first consulting their doctor.

What is a healthful diet for a person with MS? Find out here.
Medical marijuana

Studies have suggested that cannabis may help relieve pain, muscle stiffness, and insomnia. However, there is not enough evidence to confirm this.

People should also note that:

    There is a difference between using street cannabis and medical cannabis.
    Not all forms of cannabis are legal in all states.

A person should ask their doctor for advice before using cannabis, as some forms can have adverse effects. Smoking cannabis is unlikely to be beneficial, and it may make symptoms worse.

Some people have suggested that biotin may help. Find out more here.
Rehabilitation and physical therapy
Rehabilitation can help improve or maintain a person's ability to perform effectively at home and work.

Programs generally include:

Physical therapy: This aims to provide the skills to maintain and restore maximum movement and functional ability.

Occupational therapy: The therapeutic use of work, self-care, and play may help maintain mental and physical function.

Speech and swallowing therapy: A speech and language therapist will carry out specialized training for those who need it.

Cognitive rehabilitation: This helps people manage specific problems in thinking and perception.

Vocational rehabilitation: This helps a person whose life has changed with MS to make career plans, learn job skills, get and keep a job.
Plasma exchange

Plasma exchange involves withdrawing blood from the individual, removing the plasma, replacing it with new plasma, and transfusing it back into the person.

This process removes the antibodies in the blood that are attacking parts of the person's body, but whether it can help people with MS is unclear. Studies have produced mixed results.

Plasma exchange is usually only suitable for severe MS attacks.
Stem cell therapy

Scientists are looking into the use of stem cell therapy to regenerate various body cells and restore function to those who have lost it due to a health condition.

Researchers hope that one day, stem cell therapy techniques may be able to reverse the damage done by MS and restore functionality in the nervous system.
Outlook

MS is a potentially severe health condition that affects the nervous system. Progression of MS is different for each person, so it is hard to predict what will happen, but most people will not experience severe disability.

In recent years, scientists have made rapid progress in developing drugs and treatments for MS. Newer drugs are safer and more effective, and they offer significant hope for slowing disease progression.

As researchers learn more about genetic features and changes that occur with MS, there is also hope that they will be able to predict more easily which kind of MS a person will have and establish the most effective treatment from the earliest stage.

A person who receives appropriate treatment and follows a healthful lifestyle can expect to live the same number of years as a person without MS.

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Genes linked to Alzheimer's risk, resilience identified

An international team of researchers has identified a pair of genes that influence risk for both late-onset and early-onset Alzheimer's disease.

In the study, the researchers measured soluble TREM2 levels in the cerebrospinal fluid of 813 older adults, most of whom were aged 55 to 90. Of those subjects, 172 had Alzheimer's disease, 169 were cognitively normal, and another 183 had early mild cognitive impairment.

TREM2 is a protein that is believed to help microglia cells clear excessive amounts of the Alzheimer's proteins amyloid and tau from the brain.

The researchers also analyzed the participants' DNA, conducting genomewide association studies to look for regions of the genome that may influence TREM2 levels in the cerebrospinal fluid.

Common variants in the MS4A4A gene had been associated with risk for Alzheimer's, and the study also connects those genes.

"We observed TREM2 risk variants more often in people who had Alzheimer's or were mildly cognitively impaired, compared with those who were cognitively normal," said co-senior investigator. "It turns out that about 30 percent of the population in the study had variations in the MS4A4A gene that appear to affect their risk for developing Alzheimer's disease. Some variants protected people from Alzheimer's or made them more resilient while others increased their risk."

Digging further, the researchers found that variants in the MS4A4A gene cluster linked to an increase in risk for developing Alzheimer's disease are associated with lower levels of soluble TREM2 protein. The other variant, associated with higher levels of TREM2 in the cerebrospinal fluid, seemed to protect against Alzheimer's.

They validated the results in DNA from another 580 older adults. Once again, they found that higher soluble TREM2 levels in the cerebrospinal fluid seemed protective, while lower levels increased risk. And those protein levels, whether high or low, were linked to variants in the MS4A4A gene.

"For the past several years, we've been looking at TREM2 and increasing our focus on the involvement of the brain's immune cells in Alzheimer's disease," said  an assistant professor of psychiatry. "These findings give us a new therapeutic strategy to pursue, one focusing not only on neurons but on how the microglia may be involved in helping to clear damaging proteins, such as beta amyloid and tau, that are linked to Alzheimer's disease."

Those gene variants also may play a role in other diseases of the central nervous system, according to Laura Piccio, an associate professor of neurology and another co-senior author.

"By combining large genetic and spinal fluid analyses with laboratory work, we have provided strong evidence of a biological link between TREM2 and proteins in the MS4A gene cluster, both of which previously had been associated with Alzheimer's disease," the Prof. said. "We are beginning to elucidate a molecular pathway in microglia that could be critical not only in Alzheimer's disease but also in other neurodegenerative and inflammatory diseases in the central nervous system."

The results could provide researchers with new targets and a strategy for delaying the onset of Alzheimer's symptoms.

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