http://www.eurekalert.org/pub_releas...-cav091406.php

Public release date: 19-Sep-2006

Contact: James Newton
james.newton@childrens.harvard.edu
617-355-6420
Children's Hospital Boston

Can a vitamin alleviate chronic, progressive multiple sclerosis?
Ongoing nerve-fiber damage, disability prevented in animal study

------------------------------------------------------------

-------------------------------------------------------------

In mice with MS-like disease, nicotinamide delayed and reduced neurologic disability as indicated by behavioral scores (1 indicating mild weakness only in the tail; 4, paralysis involving all four limbs)....

-------------------------------------------------------------

Researchers have found a possible way to protect people with multiple sclerosis (MS) from severe long-term disability: increase nervous-system levels of a vital compound, called nicotinamide adenine dinucleotide (NAD), by giving its chemical precursor – nicotinamide, a form of vitamin B3.

Current therapies for MS mainly address the relapsing-remitting phase of the disease, but some of these have severe side effects, and most patients eventually enter a chronic progressive phase for which there is no good treatment. Using a mouse model of MS, researchers in the Neurobiology Program at Children's Hospital Boston found strong evidence that nicotinamide may protect against nerve damage in the chronic progressive phase, when the most serious disabilities occur. Their findings appear in a cover article in the September 20 Journal of Neuroscience.

MS is a neurologic disorder in which nerve fibers, or axons, are damaged through inflammation, loss of their insulating myelin coating, and degeneration. This damage disrupts nerves' ability to conduct electrical impulses to and from the brain, causing such symptoms as fatigue, difficulty walking, pain, spasticity, and emotional and cognitive changes. Current treatments mainly protect against inflammation and myelin loss, but do not completely prevent long-term axon damage.

A team led by Shinjiro Kaneko, MD, a research fellow at Children's, and senior investigator Zhigang He, PhD, also from Children's, worked with mice that had an MS-like disease called experimental autoimmune encephalitis (EAE). Through careful experiments, they showed that nicotinamide protected the animals' axons from degeneration – not only preventing axon inflammation and myelin loss, but also protecting axons that had already lost their myelin from further degradation.

Intriguingly, mice with EAE who received daily nicotinamide injections under their skin had a delayed onset of neurologic disability, and the severity of their deficits was reduced for at least eight weeks after treatment. The greater the dose of nicotinamide, the greater the protective effect. [See accompanying figure.]

On a scale of 1 to 5 (1 indicating mild weakness only in the tail, 4 indicating paralysis involving all four limbs, and 5, death from the disease), mice receiving the highest doses of nicotinamide had neurologic scores between 1 and 2, while control mice had scores between 3 and 4. All differences between treated groups and controls were statistically significant.

Mice with the greatest neurologic deficits had the lowest levels of NAD in their spinal cord, and those with the mildest deficits had the highest NAD levels. Mice that had higher levels of an enzyme that converts nicotinamide to NAD (known as Wlds mice) responded best to treatment.

Moreover, nicotinamide significantly reduced neurologic deficits even when treatment was delayed until 10 days after the induction of EAE, raising hope that it will also be effective in the later stages of MS. "The earlier therapy was started, the better the effect, but we hope nicotinamide can help patients who are already in the chronic stage," says Kaneko.

In other experiments, the researchers demonstrated that nicotinamide works by increasing levels of NAD in the spinal cord and that NAD levels decrease when axons degenerate. Finally, they showed that giving NAD directly also prevented axon degeneration.

NAD is used extensively by cells to produce energy through the breakdown of carbohydrates. Its chemical precursor, nicotinamide, has several characteristics that make it a promising therapeutic agent: it readily crosses the blood-brain barrier, is inexpensive and available in any drugstore, and its close relative, vitamin B3, is already used clinically to treat pellagra (vitamin B3 deficiency), high cholesterol, and other disorders. Although nicotinamide is thought to have few side effects, the doses used in mice would translate to much higher human doses than are normally used clinically, so would need to be tested for safety.

"We hope that our work will initiate a clinical trial, and that nicotinamide could be used in real patients," Kaneko says. "In the early phase of MS, anti-inflammatory drugs may work, but long-term you need to protect against axonal damage."

###
The research was funded by the National Multiple Sclerosis Society and the National Institute of Neurological Disorders and Stroke.

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, nine members of the Institute of Medicine and 11 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 347-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit: www.childrenshospital.org/newsroom.

http://www.southcoasttoday.com/daily...6/02health.htm

A possible advance in fight against multiple sclerosis
By LEE BOWMAN , Scripps Howard News Service

Researchers working with mice report that it may be possible to protect people with multiple sclerosis from long-term nerve damage by boosting levels of a vitamin derivative in the nervous system.
MS is a neurological disorder in which nerve fibers are damaged by inflammation thought to be triggered by the immune system's mistakenly attacking them.
Damage to nerve fibers and to their fatty insulating tissues, disrupts nerves' ability to conduct electrical impulses to and from the brain. This produces the symptoms of MS that include fatigue, difficulty in walking, pain, spasticity and emotional and cognitive changes.
Currently, MS treatments mainly protect against inflammation and loss of fatty insulating tissues, but don't completely prevent long-term scarring and breaking of the nerve fibers, for which there is no good treatment. And some of the drugs given to treat the early phases of the disease have severe side effects.
Researchers at Children's Hospital Boston, the pediatric teaching hospital for Harvard Medical School, worked with mice that had an MS-like disease.
The experiments, described Wednesday in the Journal of Neuroscience, showed that nicotinamide— a form of vitamin B3, or niacin — not only protected the animals' nerve fibers from degeneration and fatty insulating tissues loss, it also protected nerve fibers that have already lost insulation from degrading further.
"We hope our work will initiate a clinical trial, and that nicotinamide could be used in real patients," said Dr. Shinjiro Kaneko, a research fellow at Children's who led the study. "In the early phase of MS, anti-inflammatory drugs may work, but long-term, you need to protect against axonal (nerve fiber) damage."
On a scale of 1 to 5 (with 1 being only mild weakness in the tail; 4, paralysis in all four limbs, and 5, death from the disease), mice receiving the highest doses of daily nicotinamide injections under the skin had scores of 1 or 2, while mice not getting the vitamin had scores of 3 or 4.
Nicotinamide significantly reduced neurological symptoms even when treatment was delayed for 10 days after the onset of disease in the mice, raising hopes that it can be effective in the later stages of MS in people.
"The earlier therapy was started, the better the effect, but we hope nicotinamide can help patients who are already in the chronic stage," said Kaneko.
Kaneko noted that since vitamin B3 is already used medically to treat high cholesterol and other disorders, it should have few side effects in humans being treated for MS. But he noted that the doses used in the mice would translate to much higher doses than typically given to people, so new tests for safety would be needed before there could be any tests to evaluate the drug's effectiveness.

Date of Publication: September 19, 2006 on Page

http://www.pdrhealth.com/drug_info/n...nic_0183.shtml

http://www.patient.co.uk/showdoc/30003248/

Description of Nicotinamide

Hey! I'm ready to order large quantities of this stuff, anybody else? The only thing is, I don't know how much to take. I don't want to take too much and distroy my liver, but I don't want to take so little that it doesn't do much good.

Anybody taking this form of B3 (Nicotinamide), and if so how much? I hate to jump the gun, but it is an available supplement, so I might as well try it, 'cause I'm getting old waiting for a cure.

Wadda ya think?

Sounds promising but so did many other studies using mice. Somehow they don't seem to translate well to humans??? Maybe we should try to grow tails!!!

Keeping fingers crossed anyway!!

Yep, you're probably right, Judy. We have the healthiest
un-healthy Mice in the world.

On the other hand, it's a vitamin and it's cheap.