Dalfampridine Improves Cognitive Impairment in Multiple Sclerosis

Would this help post-stroke? It seemed to fail in walking post-stroke. Since I have never been able to find out if stroke demyelinates nerves in the brain, that answer may tell us whether this would work for stroke. So ask your doctor that question, 'Does stroke demyelinate nerves in the brain?'  A neurologist I saw once tried to tell me that was the case but I think he was just blowing smoke out his ass, trying to pull the stunt that I(the doctor) know more than you, so just shut up about questions.

Acorda ditches dalfampridine poststroke walking studies

Ask your doctor for help in getting this clinically tested in stroke patients, you shouldn't have to ask, it should already be part of their goals and objectives. Assuming the stroke department head is competent and actually wants to solve all the problems in stroke.

Dalfampridine Improves Cognitive Impairment in Multiple Sclerosis

By Alex Morrisson
BOSTON -- May 2, 2017 -- Treatment with dalfampridine appears to improve cognitive impairment and some cognitive functioning tasks among patients diagnosed with multiple sclerosis (MS), according to clinical trial results presented at the 2017 Annual Meeting of the American Academy of Neurology (AAN).
“Dalfampridine should be considered as an effective treatment option for cognitive impairment in multiple sclerosis,” said lead author Laura De Giglio, MD, PhD, Sapienza University, Rome, Italy, speaking here on April 26.
Dr. De Giglio and colleagues randomised subjects in a 2:1 fashion to receive either 10-mg dalfampridine twice daily or placebo for 12 weeks.
Baseline score in the Symbol Digit Modalities Test (SDMT) was a mean of 30 seconds. The primary endpoint of the study was the improvement of processing speed measured with SDMT. Four weeks after the end of treatment, evaluable patients treated with dalfampridine (n = 70) achieved a scoring increase of 9.89 seconds on the Symbol Digit Modalities Test (SDMT) compared with evaluable patients on placebo (n = 37) who achieved a scoring increase of 4.89 seconds (P = .001).
In all, 76.1% of subjects treated with dalfampridine achieved at least a 20% improvement in the SDMT compared with 41.4% of the subjects receiving placebo (P = .001).
On a variety of secondary measures, subjects taking dalfampridine also showed some improvement on spatial memory, cognitive fatigue, and the overall Multiple Sclerosis Functional Composite.
Most subjects were in their mid-to-late 40s; about 60% were female. Subjects had a diagnosis of multiple sclerosis for about 15 years.
“Thirty-five to sixty percent of multiple sclerosis patients are believed to have some cognitive dysfunction, but results of treatment for this aspect of the disease have been limited or inconsistent,” noted Dr. De Giglio.
Dalfampridine, approved in the United States to improve walking difficulty in patients with MS, is a selective neuronal potassium-channel blocker that is designed to improve conduction of action potential in demyelinated nerve fibers. The drug is believed to increase the release of neurotransmitters in synapses and at the neuromuscular junctions.
Funding for this study was provided by Biogen, Cambridge, Massachusetts.
[Presentation title: Dalfampridine Improves Cognitive Impairment in Multiple Sclerosis (MS): Results From a Randomised, Double-blind, Placebo-controlled Trial.]

Acorda ditches dalfampridine poststroke walking studies

Now if only they would analyze exactly why this didn't work so it could be applied to the next project in the strategy to get to 100% walking recovery.
http://www.fiercebiotech.com/biotech/acorda-ditches-dalfampridine-post-stroke-walking-studies

Acorda’s poststroke walking difficulties med dalfampridine doesn’t work, and the biotech is pulling the plug as it looks across to its Parkinson’s and migraine assets going forward.
The near $1 billion market cap company said its “Milestone” study “did not show sufficient efficacy to support further development of dalfampridine to improve poststroke walking difficulties (PSWD).” Its shares dropped sharply premarket this morning by 13%.
So what happened? In a statement, the biotech said the measure of its success was the proportion of participants who showed at least a 20% improvement on the Two Minute Walk Test (2MinWT) at week 12 as compared to baseline.
In the Milestone test, however, the biotech’s med saw just 23 out of 121 (19%) of those receiving the higher 10-mg dose of dalfampridine twice a day, and 17 of 121 (14%) participants getting the lower 7.5-mg dose of dalfampridine, showing at least that 20% improvement on the 2MinWT. On a dummy therapy, 17 out of 126 (13.5%) achieved the same.
Those taking the drug also seem to have had more falls, as well as urinary tract infections and dizziness.
While no seizures were reported in the dalfampridine 10-mg group, two seizures were reported in the 7.5-mg group and three in the placebo group.
The drug is already approved as a treatment to help certain multiple sclerosis patients walk better under the name Ampyra (dalfampridine).
Ron Cohen, president and CEO of Acorda, said he was “disappointed by this outcome.”
He went on: “The study indicated there was activity related to walking in people with PSWD, as suggested by the prior Phase II study, but overall this was not sufficiently clinically meaningful. I want to express our gratitude to the study participants, their care partners and clinicians, who gave their time and commitment to this research.”
He said that the co would now refocus on the new pipeline it has been building up over the past three years.
This includes further work on its late-stage Parkinson’s disease therapies, CVT-301 and tozadenant, as well as advancing its earlier stage assets, CVT-427 in migraine, SYN120 in Parkinson’s disease dementia, and rHIgM22 in MS.

Take part in the Phase 3 clinical study for people with walking problems at least 6 months after an ischemic stroke

Join the MILESTONE(TM) Stroke Study per the NSA.

Your choice. Ask your doctor why they haven't told you about this study before you ask them about it?

The actual study here with the drug being tested:

A Study to Evaluate the Efficacy and Safety of Two Dose Strengths of Dalfampridine Extended Release Tablets for Treatment of Stable Walking Deficits in Post-Ischemic Stroke (MILESTONE℠)

 The NSA news release:

Take part in the Phase 3 clinical study for people with walking problems at least 6 months after an ischemic stroke

Why is this study important?

Currently, there are no FDA approved medications available for improving the walking problems in these patients. Physical therapy and rehabilitation are the current mainstays of treatment to assist with walking problems following a stroke. Pharmaceutical companies use medical research studies such as the MILESTONE^SM Stroke Study to learn more about unapproved medications before they are made available to the public. By taking part in this study, you will be making a contribution to stroke therapy research.

What are the challenges related to this study?

The investigational medication has been approved as a treatment to improve walking problems associated with a different disease, however not in patients recovering from a stroke. This use is still investigational. The investigational medication is being tested in people who have had an ischemic stroke, because this condition has some nervous system changes that may be similar to what is seen in the disease for which this medication is approved. In an earlier study with about 80 participants who have had a stroke, there was some initial evidence of improvement in walking while taking the investigational medication twice a day for 2 weeks, when compared with a placebo.

TO PRE-QUALIFY FOR THIS STUDY, YOU MUST: be 18 years of age or older have had an ischemic stroke 6 months ago or longer have walking problems as a result of the ischemic stroke, such as walking more slowly or needing to use a cane or walker. YOU MUST NOT: have a history of seizures, except simple febrile seizures have moderate or severe renal impairment have had Botox within the past 2 months be pregnant, breastfeeding, or planning to become pregnant (if you are a woman able to have children).

All study-related visits, assessments, and study medication will be provided to participants at no cost. In addition, compensation for time and travel may be provided.

OR CALL

1-866-735-3667

Pill Could Reverse Effects of a Stroke Long After It Hits

Have your doctor report back to you when the clinical trial results are released.
http://www.technologyreview.com/news/428026/pill-could-reverse-effects-of-a-stroke-long-after-it-hits/
For the 800,000 people in the United States who suffer a stroke each year, the window for drug therapy closes in the first few hours after the attack. That leaves some seven million stroke survivors in this country alone with no medical alternative beyond physical therapy. A small pharmaceutical company in New York hopes to change that with a drug that may help patients regain some of their lost mobility six months or more after a stroke.
Strokes happen when blood stops flowing to part of the brain, often due to a blood clot. Without blood to bring new oxygen, cells in the affected region start to die. If the symptoms of stroke are recognized quickly enough and the victim is brought to a hospital within a few hours, doctors can administer a clot-dissolving drug to minimize the damage. But only a small fraction of stroke patients seek medical attention soon enough for this intervention.

“If they miss this therapeutic window, the consequences are heavier, so it’s important to be able to do something for those patients who miss that window,” says Francesca Bosetti, a stroke expert with the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
In the future, stroke patients who miss this window and are affected by reduced mobility long after their stroke may be able to turn to a drug that helps damaged nerves transmit electrical signals in the brain.
Earlier this year, Acorda Therapeutics reported that the compound dalfampridine improved motor function in both the forelimbs and hind limbs of rats that had suffered a stroke. This month, the company began recruiting patients for a clinical trial to test the effects of the compound in human stroke patients. Acorda plans to enroll about 70 people who have had a stroke at least six months prior. “That’s the time that deficits seem to stabilize, so we can eliminate naturally occurring improvements in patients,” says Jeff MacDonald, an Acorda spokesman.
Acorda is focusing on neurological disorders at a time when many pharmaceutical companies seem to be turning away from such maladies. The company was founded in 1995 to treat spinal-cord injuries and has since taken on other neurological conditions, including multiple sclerosis and stroke. The company originally licensed dalfampridine from drugmaker Elan in the hope of using it to treat spinal-cord injuries, but instead it found more success in treating multiple sclerosis patients. “We followed it to where it was leading,” says Andrew Blight, chief scientific officer for Acorda.
Spinal-cord injuries still garner a lot of focus from the company, which hopes to begin testing a compound licensed from Medtronic that protects neurons from the wave of cell death that follows the initial injury. Medtronic had already shown the compound to be safe in healthy patients, and later this year, Acorda plans to test its efficacy in patients in the first hours after a spinal-cord injury.
Patients with injured spinal cords are not nearly as numerous as stroke patients, “but if you are talking about costs to society, spinal-cord injuries are extremely expensive,” says Naomi Kleitman, a spinal-cord injury expert with NINDS. “They tend to happen in fairly young people who need a lot of medical and assistive help if they have severe injuries.”
The company is also looking to treat longer-standing spinal-cord injuries with a drug that would help break down the scar tissue that forms around a spinal-cord injury. The scar tissue is thought to prevent nerves from establishing the new connections that may help patients recover some functionality. The product is still in early development, and one challenge will be devising a method to deliver the large scar-busting molecule to its target site.
Despite the pressing need, the small market for spinal-cord injury drugs may be one reason the condition doesn’t get a lot of attention from pharmaceutical giants. “No one else wants to develop compounds to treat spinal-cord injury as seriously as Acorda,” says Edward Hall, a neurologist and spinal-cord and brain-injury specialist at the University of Kentucky in Lexington. “These aren’t going to be billion-dollar-a-year products.”
Numbers will not be an issue for long-term stroke patients. Stroke is the leading cause of adult disability, and the number of people living with its effects is growing. “We are getting better at preventing stroke death, but the incidence is going up because the population is aging, and age is the greatest risk factor,” says S. Thomas Carmichael, a neurologist and neurorepair researcher at the University of California, Los Angeles.
Relatively few groups are working on treating the effects of a stroke more than six months after it occurred, says Carmichael, in part because the disorder is tricky to model in lab animals.
“It’s great for the field that [Acorda] is there,” he says. “Right now, there are no pharmaceutical options.”
However, Carmichael cautions that even six months or more after a stroke, patients can respond to focused rehabilitative intervention, which suggests that movement is an important part of recovery. “You have to pay attention to physical activity.” A patient’s own activity level can confound a trial if it’s not well monitored, but it could also lead to the greatest outcomes, he says, if made a part of it.

Acorda Therapeutics Announces Data Showing Dalfampridine Improves Motor Function in Preclinical Model of Post-Stroke Deficits Published in Stroke

Well, ask your doctor if this would help you. For chronic use it seems.
http://www.pipelinereview.com/index.php/2013050950926/Small-Molecules/Acorda-Therapeutics-Announces-Data-Showing-Dalfampridine-Improves-Motor-Function-in-Preclinical-Model-of-Post-Stroke-Deficits-Published-in-Stroke.html
Acorda Therapeutics, Inc. (Nasdaq: ACOR) today announced that data showing treatment with dalfampridine improved motor function in a preclinical model of post-stroke deficits have been published online ahead of print on May 7^th in Stroke, a peer-reviewed journal of the American Heart Association. The data will be included in the July 2013 print edition of Stroke. Dalfampridine is the active ingredient in AMPYRA^® (dalfampridine) Extended Release Tablets, 10 mg.
“These preclinical data showed that dalfampridine can improve motor function long after a stroke, when the natural recovery process has ended and stable deficits are likely to persist over time. The results informed our decision to conduct a recently completed proof-of-concept study in humans, which indicated that dalfampridine improved walking in people with post-stroke deficits,” said Andrew R. Blight, Ph.D., Acorda Therapeutics’ Chief Scientific Officer. “More than half of the nearly seven million people in the United States who live with the long term effects of a stroke have lasting mobility impairment, but there are no established treatments other than physical therapy to address these impairments. New therapies are needed, and we are moving forward with development of dalfampridine extended release tablets in this indication.”
More at link.

A Phase 1/Phase 2 Study of Dalfampridine 10mg Extended Release Tablet in Subjects With Chronic Deficits After Ischemic Stroke

The actual trials I blogged about. Note the term chronic. If your doctor doesn't know about this, ask why.  Consult your doctor before joining.
Previous post;
http://oc1dean.blogspot.com/2012/05/acorda-therapeutics-presents.html

Recruitment here: Florida, Georgia, Virginia
http://www.clinicaltrials.gov/ct2/show/NCT01605825?term=Acorda&rank=4

Acorda Therapeutics Presents Preclinical Data Showing Dalfampridine Improves Motor Function in Chronic Stroke

Note the word chronic.
This is also being used as a drug to help MS patients walk, see here:
http://ir.acorda.com/phoenix.zhtml?c=194451&p=irol-newsOtherArticle&ID=1701026&highlight=
This does bring up the question, if it helps stroke patients does that mean that demyelination occurs as part of the stroke damage?
http://ir.acorda.com/phoenix.zhtml?c=194451&p=irol-newsOtherArticle&ID=1656337&highlight=
Acorda Therapeutics, Inc. (Nasdaq: ACOR) presented data showing that treatment with dalfampridine improved motor function in a preclinical model of stroke, with treatment initiated at least four weeks following the ischemic event. These data were presented on February 2 at the American Heart Association/American Stroke Association International Stroke Conference in New Orleans, LA. Dalfampridine, also known as 4-aminopyridine, is the active chemical ingredient in AMPYRA^® (dalfampridine) Extended Release Tablets, 10 mg.
“These are the first preclinical data to show an oral pharmacologic treatment can improve function in chronic, or long term, stroke. We are excited by these results and plan to begin proof-of-concept human clinical trials of AMPYRA in people with chronic stroke later this year,” said Andrew R. Blight, Ph.D., Acorda Therapeutics’ Chief Scientific Officer. “The majority of the nearly seven million people in the United States who live with the long term effects of a stroke have motor function deficits, such as walking impairment, but there are no established treatments other than physical therapy to address these impairments.”
A late-breaking science presentation, entitled “Dalfampridine Improves Sensorimotor Function in Rats with Chronic Deficits Following Middle Cerebral Artery Occlusion,” presented by Acorda scientist Jennifer Iaci, reviewed data from three study groups that received treatment beginning four weeks after a permanent middle cerebral artery occlusion (pMCAO). The neurological impairments that result are expected to be permanent by four weeks, which represents the chronic stage of stroke. Each group received three treatment phases over the course of the study: high and low doses of dalfampridine, and placebo. The order of the treatment phases was different for each group, with a 10 day washout period between each phase.
Researchers assessed functional improvement using a battery of standard motor function tests in both the forelimbs and hind limbs. In each of the three study groups, treatment with dalfampridine resulted in significant improvement in function compared to placebo across all measures during the respective treatment periods. Improvements in the high dose phase were consistently better than those seen in the low dose phase.
“In addition to the seven million Americans living with the consequences of a prior stroke, there are close to 800,000 people in the United States who have new stroke events each year. The resulting disability has a major impact on the person who suffers the stroke as well as on their caregivers, and places a significant burden on the healthcare system,” said Seth Finklestein, M.D., Chairman and Chief Scientific Officer of Biotrofix, a preclinical research organization that conducted research for this study in partnership with Acorda. “These are the first data from a well-controlled preclinical study that have demonstrated improvement in motor function related to walking and upper body movement. Developing a therapeutic option that can improve function would represent a potential major advance in the standard of care for stroke survivors.”
Acorda plans to begin a proof-of-concept trial of AMPYRA in stroke by the end of 2012. (I'm going to try to find out how to get involved)Go here to apply for the trial:
http://oc1dean.blogspot.com/2012/06/phase-1phase-2-study-of-dalfampridine.html
This study will evaluate the use of AMPYRA in stroke patients with chronic neurologic deficits, including walking impairment.
AMPYRA is approved in the United States as a treatment to improve walking in patients with multiple sclerosis (MS). This was demonstrated by an improvement in walking speed. AMPYRA is known as prolonged-, modified-, or sustained-release fampridine (FAMPYRA^®) in some countries outside the United States.
Important Safety Information
AMPYRA can cause seizures; the risk of seizures increases with increasing AMPYRA doses. AMPYRA is contraindicated in patients with a prior history of seizure. Discontinue AMPYRA use if seizure occurs.
AMPYRA is contraindicated in patients with moderate or severe renal impairment (CrCl less-than or equal to 50 mL/min); the risk of seizures in patients with mild renal impairment (CrCl 51-80 mL/min) is unknown, but AMPYRA plasma levels in these patients may approach those seen at a dose of 15 mg twice daily, a dose that may be associated with an increased risk of seizures; estimated CrCl should be known before initiating treatment with AMPYRA.
AMPYRA should not be taken with other forms of 4-aminopyridine (4-AP, fampridine), since the active ingredient is the same.
Urinary tract infections were reported more frequently as adverse reactions in patients receiving AMPYRA 10 mg twice daily compared to placebo.
The most common adverse events (incidence greater-than or equal to 2% and at a rate greater than the placebo rate) for AMPYRA in MS patients were urinary tract infection, insomnia, dizziness, headache, nausea, asthenia, back pain, balance disorder, multiple sclerosis relapse, paresthesia, nasopharyngitis, constipation, dyspepsia, and pharyngolaryngeal pain.
For full U.S. Prescribing Information and Medication Guide for AMPYRA, please visit: www.AMPYRA.com.
About Acorda Therapeutics
Acorda Therapeutics is a biotechnology company focused on developing therapies that restore function and improve the lives of people with MS, spinal cord injury and other neurological conditions.
Acorda markets AMPYRA^® (dalfampridine) Extended Release Tablets, 10 mg, in the United States as a treatment to improve walking in patients with multiple sclerosis (MS). This was demonstrated by an improvement in walking speed. AMPYRA is marketed outside the United States as FAMPYRA^® (prolonged-release fampridine tablets) by Biogen Idec under a licensing agreement from Acorda. AMPYRA and FAMPYRA are sold under a license from Alkermes Pharma Ireland Limited and manufactured by Alkermes Pharma Ireland Limited and other parties.
The Company also markets ZANAFLEX CAPSULES^® (tizanidine hydrochloride) and Zanaflex tablets, a short-acting drug for the management of spasticity.
Acorda is developing an industry-leading pipeline of novel neurological therapies. The Company is studying AMPYRA to improve a range of functional impairments caused by MS, as well as its use in other neurological conditions, including cerebral palsy and chronic stroke. In addition, Acorda is developing clinical stage compounds AC105 for acute treatment of spinal cord injury and GGF2(see here for GGF2) for treatment of heart failure. GGF2 is also being investigated in preclinical studies as a treatment for neurological conditions such as stroke and spinal cord injury. Additional preclinical programs include rHIgM22, a remyelinating monoclonal antibody for the treatment of MS, and chondroitinase, an enzyme that encourages nerve plasticity in spinal cord injury.

Ask your doctor, this was reported on Feb. 3, 2012 so they should be well aware of this by now.

Acorda Therapeutics Presents Preclinical Data Showing Dalfampridine Improves Motor Function in Chronic Stroke

First ever data to demonstrate improvement in motor function following stroke with oral drug treatment initiated several weeks after event
http://eon.businesswire.com/news/eon/20120203005039/en/acorda/ampyra/multiple-sclerosis
Acorda Therapeutics, Inc. (Nasdaq: ACOR) presented data showing that treatment with dalfampridine improved motor function in a preclinical model of stroke, with treatment initiated at least four weeks following the ischemic event. These data were presented on February 2 at the American Heart Association/American Stroke Association International Stroke Conference in New Orleans, LA. Dalfampridine, also known as 4-aminopyridine, is the active chemical ingredient in AMPYRA^® (dalfampridine) Extended Release Tablets, 10 mg.

“These are the first preclinical data to show an oral pharmacologic treatment can improve function in chronic, or long term, stroke. We are excited by these results and plan to begin proof-of-concept human clinical trials of AMPYRA in people with chronic stroke later this year”

“These are the first preclinical data to show an oral pharmacologic treatment can improve function in chronic, or long term, stroke. We are excited by these results and plan to begin proof-of-concept human clinical trials of AMPYRA in people with chronic stroke later this year,” said Andrew R. Blight, Ph.D., Acorda Therapeutics’ Chief Scientific Officer. “The majority of the nearly seven million people in the United States who live with the long term effects of a stroke have motor function deficits, such as walking impairment, but there are no established treatments other than physical therapy to address these impairments.”

A late-breaking science presentation, entitled “Dalfampridine Improves Sensorimotor Function in Rats with Chronic Deficits Following Middle Cerebral Artery Occlusion,” presented by Acorda scientist Jennifer Iaci, reviewed data from three study groups that received treatment beginning four weeks after a permanent middle cerebral artery occlusion (pMCAO). The neurological impairments that result are expected to be permanent by four weeks, which represents the chronic stage of stroke. Each group received three treatment phases over the course of the study: high and low doses of dalfampridine, and placebo. The order of the treatment phases was different for each group, with a 10 day washout period between each phase.

Researchers assessed functional improvement using a battery of standard motor function tests in both the forelimbs and hind limbs. In each of the three study groups, treatment with dalfampridine resulted in significant improvement in function compared to placebo across all measures during the respective treatment periods. Improvements in the high dose phase were consistently better than those seen in the low dose phase.

“In addition to the seven million Americans living with the consequences of a prior stroke, there are close to 800,000 people in the United States who have new stroke events each year. The resulting disability has a major impact on the person who suffers the stroke as well as on their caregivers, and places a significant burden on the healthcare system,” said Seth Finklestein, M.D., Chairman and Chief Scientific Officer of Biotrofix, a preclinical research organization that conducted research for this study in partnership with Acorda. “These are the first data from a well-controlled preclinical study that have demonstrated improvement in motor function related to walking and upper body movement. Developing a therapeutic option that can improve function would represent a potential major advance in the standard of care for stroke survivors.”

Acorda plans to begin a proof-of-concept trial of AMPYRA in stroke by the end of 2012. This study will evaluate the use of AMPYRA in stroke patients with chronic neurologic deficits, including walking impairment.

AMPYRA is approved in the United States as a treatment to improve walking in patients with multiple sclerosis (MS). This was demonstrated by an improvement in walking speed. AMPYRA is known as prolonged-, modified-, or sustained-release fampridine (FAMPYRA^®) in some countries outside the United States.