Botox Research And News

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Injections of botulinum toxin A (Botox) were a significant help to multiple sclerosis patients whose disease causes arm tremors, according to a small study reported here.

In a placebo-controlled crossover trial involving 25 patients, Botox injected into the affected muscles significantly improved the tremors, said Anneke van der Walt, MBChB, of Royal Melbourne Hospital in Australia.

The treatment also allowed many of the patients to again perform simple activities such as handwriting and drinking from open cups that the tremors had made difficult or impossible, van der Walt told attendees at the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis.

Currently there is no specific treatment for MS-related tremors, she explained. The present standard of care involves anticonvulsant drugs such as levetiracetam (Keppra) or carbamazepine, with a variety of other agents often used as well. These include benzodiazepines, beta-blockers, and even the anti-nausea drug ondansetron.

Van der Walt described these medications as "unrewarding" and indicated that nonsurgical approaches such as thalamotomy and deep brain stimulation had substantial side effects and lacked confirmation of long-term efficacy.

Botox, on the other hand, is considered safe when injected carefully and has been found helpful in a host of conditions involving abnormal muscle activity, ranging from overactive bladder to migraine.

The 25 patients in the study included some with bilateral tremors, such that a total of 33 arms were treated and evaluated, after excluding one dropout and two patients who experienced MS relapse during the study. About three-quarters of participants had secondary progressive MS, with mean disease duration of 17 years (SD 8.5) and mean duration of tremor of 6.5 years (SD 5.1).

The median of both EDSS disability score and Unified Dystonia Rating Scale score was 5.5.

Patients received injections of botulinum toxin A or placebo targeted to their specific tremor patterns. A maximum of 100 IU of Botox was given in each injection.

Evaluations were conducted at baseline and six and 12 weeks after the treatment. At that point, participants crossed over to the other treatment for an identical series of injections and assessments.

The primary outcome measure was change from baseline in Bain scores for ability to hand-write a standard sentence, drawing of an Archimedes spiral, and a composite of tremor severity.

A variety of other ratings were secondary outcomes. These included scores for postural, action, intention, and rest tremors as well as for abilities to perform ordinary tasks such as drawing straight lines, pouring liquids, and drinking from a cup.

Videos were taken at baseline and at each post-treatment evaluation of participants performing these tasks.

Van der Walt showed clips of one middle-age male patient who had major improvement following the toxin injections.

At baseline, the man's left hand shook violently as he tried to write on a piece of paper and to hold a cup to his lips.

The "after" video showed him successfully drawing the Archimedes spiral, pouring water into a container without spilling, and drinking from a cup. However, it wasn't a total cure, as his hand still shook noticeably during these activities.

For all 33 arms included in the study, the mean decrease in Bain scores for tremor severity following the active Botox injections was about 2.0 at six and 12 weeks. The writing and drawing scores both declined by close to 1.0.

Very slight increases in Bain scores for all three components were seen in the averages following placebo injections, van der Walt reported. P values for all comparisons between Botox and placebo were less than 0.001.

Postural and action tremors both showed significantly greater improvement with Botox than with placebo at the six- and 12-week evaluations. However, resting and intentional tremors did not improve.

Not all participants showed significant improvements in all functional tasks at both evaluations, though when statistical significance was lacking the trend was still strong.

For example, improvements in ability to drink from a cup fell just short of significant at six weeks (P=0.069) but reached significance at 12 weeks (P=0.009). The opposite pattern was seen for pouring water into a container.

The major adverse effect associated with toxin injections was weakness in the injected arm, van der Walt said. It was reported in 42% of Botox-treated arms versus 6% of those receiving placebo shots.

None of the weakness was severe, she added; most was rated as moderate, defined as feeling weak but still able to use it.

In all cases, moreover, the weakness did not last beyond two weeks after the injections.

In response to an audience question, van der Walt said that many participants had continued to receive Botox injections in the hospital's outpatient clinic and there seemed to be no loss of effectiveness with repeated treatment. The weakness effect also appeared to decline with additional injections.

Session co-moderator Jürg Kesselring, MD, of the Neuroscience Center in Zurich, Switzerland, complimented van der Walt on the research.

"This is important because we are so desperate for something to offer our tremor patients," he said.

The study was funded by the RMH Neuroscience Foundation and Box Hill MS Research Fund. Allergan provided Botox free of charge.

Van der Walt reported grant funding and/or direct payments from Bayer, Biogen Idec, Merck Serono, and GlaxoSmithKline.

Kesselring has served on trial oversight committees and/or advisory boards for Biogen, Novartis, Serono, Schering, and Wyeth.

Primary source: ECTRIMS/ACTRIMS Triennial Meeting
Source reference:
van der Walt A, et al "Botulinum toxin type A for the treatment of disabling tremor in multiple sclerosis: a double-blind, randomised controlled study" ECTRIMS/ACTRIMS 2011; Abstract 50.

Source: MedPage Today © 2011 Everyday Health, Inc.(21/10/11)

Botox, a drug famous for smoothing out wrinkles, could make life a little easier for people with urinary incontinence. By paralyzing the muscular lining of the bladder, the drug decreases the urgency and frequency of urination.

Botox maker Allergan has applied for Food and Drug Administration approval in people with multiple sclerosis and spinal cord injury whose conditions result in bladder overactivity.

"Those people are very much affected by this," said Caroline Van Hove, Allergan's vice president of corporate affairs. "The conditions make the bladder muscle involuntarily contract, and that causes patients to have to go to the bathroom frequently and unexpectedly."

Approval could come by the end of the year, potentially making urinary incontinence the eighth condition treated with Botox. Only one use is cosmetic; the other conditions include chronic migraine and spasticity.

"The uses of Botox are increasing," said Van Hove, adding that medical indications currently account for roughly half of the drug's $1.4 billion in worldwide sales, the remainder coming from cosmetic uses. "With the new uses, definitely that 50-50 split will sway more towards therapeutic."

There are other drugs that perform multiple roles, including a skin cancer cream used to smooth out your facial wrinkles, a baldness drug to protect against prostate cancer, and a drug for enlarged prostate and possibly prostate cancer that may stop baldness.

Once a drug has been approved for one use, doctors can prescribe it "off-label" when it is shown to be useful for something else. And an increasing number of drugs are prescribed in this manner. Off-label use of medicines accounts for about one fifth of all prescriptions, according to a 2008 study in the New England Journal of Medicine.

Many of these off-label uses meet with controversy and questions about their value, particularly since the FDA has not yet approved them. (As a result, drug companies cannot advertise off-label uses.) But in other cases, the alternative uses are well-known in the medical community -- though perhaps not among the general public -- and are regularly exploited.

Source: ABC News Copyright 2011 ABC News Radio (08/08/11)

Upper limb spasticity may occur following a spinal cord or traumatic brain injury or in patients affected by multiple sclerosis or adults with a history of cerebral palsy. FDA approved the drug to treat spasticity in flexor muscles, a condition that can result from stroke, brain injury or multiple sclerosis.

Source: RTT News © 2010 RTTNews (10/03/10)

Anjali Shah, MD, Assistant Professor, Divisions of Physical Medicine and Rehabilitation and Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, and colleagues reported on data from 19 patients whose spastic foot drop was treated with botulinum toxin type A injections.

Nearly 90% of MS patients report the presence of spasticity, and lower-extremity spasticity increases the energy of walking and aggravates fatigue, Dr. Shah pointed out. Oral antispasticity medications can exacerbate fatigue and decrease cognitive functioning.

Botulinum toxin type A injections focally target spasticity, and do not cause fatigue; there are, however, limited data on the use of such injections to specifically treat spastic foot drop due to plantar flexor spasticity in MS patients.

According to the study protocol, 150 units of botulinum toxin type A diluted in 1 cc of preservative-free saline were injected into the medial gastrocnaemius muscle, lateral gastrocnaemius muscle, and soleus muscle.

Electrical stimulation was used to localise the motor points in the target muscles.

Patients underwent 6 to 8 weeks of physical therapy.

Overall, 74.7% of patients have returned for repeat botulinum toxin type A injections.

Patient self-report surveys revealed improved ambulation with less tripping or toe drag, improved driving ability, and less fatigue.

Results document significant improvement in spasticity (P = .1) and emotional quality of life (P = .035).

Dr. Shah cautioned that the study was limited by small sample size and the use of varying physical-therapy programs between subjects.

[Presentation title: Botulinum Toxin in the Treatment of Spastic Foot Drop in Multiple Sclerosis: An Analysis of the Effects on Gait, Fatigue and Quality of Life. Abstract P03.070]

Source: Doctor's Guide (c) 1995-2008 Doctor's Guide Publishing Limited (18/04/08)

Bladder problems are a common and disabling symptom of MS where both storage and emptying processes can be disrupted. Incontinence is common and being unable to 'hold on' (known as urgency) is understandably considered by many people with MS to be one of the most troubling symptoms they face.

In the recent research, carried out at the National Hospital for Neurology and Neurosurgery, 43 people with MS who had severe incontinence problems were treated with botulinum neurotoxin type A (Botox (R)) bladder muscle injections. The action of the injection on the bladder is complex but its overall effect is to reduce involuntary contractions and so reduce frequency of urination and urgency.

The GBP200,000 study showed significant improvements in incontinence episodes and the frequency of urination both day and night. There were also sustained improvements in all quality of life measures used and frequency of urination returned to near normal.

Dr Laura Bell, Research Communications Officer for the MS Society, said: "Living with symptoms such as bladder problems can be extremely distressing and restrictive, but this type of treatment can make a tangible and substantial improvement to people's lives and we hope it will become part of standard care for people with MS who need it."

The typical duration of the effect of the treatment was 10 months and similar results were seen with repeat treatments.

This treatment is not yet licensed in the UK and is consequently not yet widely available for people with MS.

Professor Clare Fowler, Consultant in Uro-Neurology at The National Hospital for Neurology and Neurosurgery said: "This study was done as part of a research investigation and the treatment is not widely available. This is because bladder injections of Botox(R) have not yet been licensed and although studies by the pharmaceutical company are ongoing it will probably take a few more years.

"This research has been extremely valuable in establishing a clinical method, researching why the treatment works so very well, and providing an opportunity to demonstrate the minimally invasive injection technique to more than 60 visitors, mostly UK consultant urologists, who attended as observers."

Further clinical trials to ascertain its effect in people with MS are currently underway. More information about clinical trials can be found at http://www.clinicaltrials.gov 

Source: MS Society (27/11/07)

Dr. Christopher Smith, assistant professor of urology at BCM, said an international multi-center study using Botox® to treat these patients is currently ongoing. He will direct the BCM part of the study.

"People with spinal cord injuries or multiple sclerosis are particularly prone to developing overactive bladder because the normal nerve pathways between the bladder and brain become interrupted," said Smith. "In these conditions, the bladder becomes overactive leading to urinary symptoms of frequency, urgency and possibly incontinence."

Botox® is a commercial preparation of botulinum toxin A that works by preventing nerve impulses from reaching the muscle.

"Botox® is the most potent drug known to man," said Smith. "It's amazing how medicine can utilize such an agent for therapeutic benefit. If you focally inject it in small quantities within the bladder, one can reduce overactive bladder symptoms without side effects associated with oral medications."

Botox® is advantageous because it is a durable yet reversible treatment, with symptom relief lasting between six to 12 months.

"Before Botox®, the only option left for a patient with refractory overactive bladder symptoms was to undergo extensive abdominal surgery, using the intestines to enlarge the bladder. This treatment requires a prolonged recovery period and, for the most part, is considered irreversible," said Smith. "Patients often prefer the reversible and less invasive option of Botox® injection."

Past studies show the drug is effective, but results from treatment in more patients are needed.

Source: Baylor College of Medicine © 1998 - 2007 Baylor College of Medicine® (15/09/07)

Botulinum Toxin, commonly knows as Botox, can paralyse and kill if consumed in contaminated food. But it's now safely used, in a purified form, as a medicine to control certain conditions marked by involuntary muscle contractions. Spasticity: This is a condition that occurs after a stroke, in multiple sclerosis and cerebral palsy patients or those suffering from traumatic brain injuries. Muscles become overactive and tighten uncontrollably. These spasms cause pain and can prevent a person from moving normally.

HOW IT WORKS: Once in the body, the toxin binds to nerve endings at the point where the nerves join muscles. This prevents the nerves from signaling the muscles to contract. The result is weakness and paralysis in that muscle. Botox is not approved by the FDA to treat spasticity, but doctors can prescribe the medication if they think it will be helpful.

HOW LONG DOES IT LAST? The drug injections usually don't manifest symptoms of recovery until a few days after the injections. The effects are usually long-lasting, however, and depending on the amount and where it was injected; Botox therapy can last from four to eight months.

SIDE EFFECTS: Botox therapy is a safe and effective treatment when given in very small amounts by a qualified neurologist. Some patients experience temporary weakness in the group of muscles being treated. Flu-like symptoms develop in some, but doctors say it is rare.

Source: ABCChicago.com Copyright ©2007 ABC Inc., WLS-TV Chicago

Christopher Chapple, a visiting professor at Sheffield Hallam University, said poisonous botulinum toxin could be used therapeutically to treat bladder storage and sensation problems such as incontinence and cystitis. Professor Chapple, who is carrying out new research into the treatment at the University's Biomedical Research Centre, said it had successfully helped eighty per cent of cases during recent trials.

He explained in a lecture at Sheffield Hallam that a simple injection of the substance into the bladder lining could bring relief to some of the ten per cent of people in the UK who currently suffer from an overactive bladder, which is resistant to other drug therapy.

He said: "Doctors are now realising the role of the bladder lining as the cause of problems to do with frequent or painful passing of urine. By injecting the patient's bladder lining with botulinum toxin, we can block the release of nerve transmitter substances and sensory nerves, which means that the patient doesn't feel the need to go to the toilet as often. It also means we don't have to rely on intensive drug therapy, or invasive surgery.

"Around ten per cent of the current UK population has an overactive bladder, while nearly a third of us will experience bladder storage or sensation problems at some point in our lives.

"The bladder normally stores urine at a low pressure, until it can be passed at a socially acceptable time, but some people have problems storing urine and need to go frequently, and urgently. Problems can occur with age, or sometimes as the result of a neurological disorder such as multiple sclerosis.

"Imagine you've come home after a few drinks, you need to pee, and you're fumbling to get the key in the door - that's the sensation some of these people experience every day."

He added: "Treatment with botulinum toxin has been successful in eighty per cent of cases so far. Work is still ongoing, but there is no doubt that it is a major advance that will really improve sufferers' quality of life."

Botulinum toxin, commercially known as Botox, is highly toxic, but is used in minute doses to control muscle spasms. Demi Moore and Madonna have reportedly benefited from its cosmetic, wrinkle-softening effects.

The simple bladder lining treatment lasts between three and six months, and can be administered to outpatients under local anesthetic.

Around fifty people have currently been treated with the botulinum toxin treatment. Professor Chapple and his team are now involved in clinical trials, and will publish further findings at the end of the current, 18-month long research project.

Professor Chapple has a specialist interest in reconstructive surgery and is also working on engineering tissue to carry out urethral reconstruction. Other research is ongoing in the research group to investigate the underlying problems behind bladder and prostate problems.

Christopher Chapple is a Consultant Urological Surgeon at the Royal Hallamshire Hospital, part of Sheffield Teaching Hospitals NHS Trust.

He spoke at Sheffield Hallam University on Wednesday 21 February, 2007.

Source: News-Medical.Net©2007 News-Medical.Net (21/02/07)

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