Multiple Sclerosis Experiment

Cody Munoz

The human body is amazingly physically capable and is able to create a number of complex movements and generate varying amounts of force, with varying speed and control of the movement due to the function of the body’s Central Nervous System. The Central Nervous System transmits messages from the brain to the part of the body a person wishes to move by using nerve fibers very rapidly, and this results in humans being able to complete a number of complex movements in very controlled manners and at considerably fast paces. However, sometimes the transmission of messages from the brain to the Spinal Cord can become disrupted, and this leads to less control of movements and can lead to movements becoming slowed down or even stopped

in severe cases. An example of a disease in which this would occur is Multiple Sclerosis, in which the myelin sheath, which insulates the nerve fibers transmitting messages from the brain to various parts of the body, wears away and thus interferes with the ability of the nerve fibers to transmit messages from the brain. This leads to messages being slowed down or not reaching their destination, which can lead to muscle weakness or fatigue, loss of coordination in the muscles, muscle spasms, or even paralysis. This is considered an autoimmune system disease in which symptoms just come and go, but nonetheless it is very serious and is a very difficult disease for those that suffer from it. Clearly, this is a serious disease that is worth investing time and research into battling, and one drug that is currently going through clinical trials and is believed to work against Multiple Sclerosis by increasing the ability of nerve fibers to create and carry electrical impulses and therefore transmitting messages better, is an experimental drug called Fampridine-SR(Sustained-Release). The mechanism of action it takes is by acting to close potassium channels. In Multiple Sclerosis, when the myelin sheath protecting nerve fibers becomes damaged, potassium leaks out of the cells and the voltage potential is lost in the fibers, to varying extents, and as a result, the slowing or stopping of message transmissions occurs. Fampridine-SR acts by inhibiting the opening of these negatively altered ion channels, and by inhibiting the opening of these channels it prevents potassium from leaking out of through these channels, allowing the voltage potential in the nerve fibers to be maintained, and permitting transmission of messages originating from the brain. It is believed that Fampridine-SR could combat the effects of Multiple Sclerosis by allowing messages to be transmitted and preventing the many symptoms and effects that occur in the human body when messages from the brain to muscles and other parts of the body are disrupted. Fampridine-SR is a very promising drug with some very positive possible outcomes for treating Multiple Sclerosis that has been going through investigations in clinical trials, and seems to be very promising.
One clinical trial examining the effects of Fampridine-SR on Multiple Sclerosis is a Phase 2 study in which participants were affected with the disease, were of both genders, and ranged from ages 18 to 70. In addition, all participants were required to have the ability to walk with or without an assisted device and could not be pregnant or participating in other trials. Dosing regiments for this trial included a placebo drug for 15 weeks, and 3 different doses of 10mg, 15mg, and 20mg of Fampridine-SR, administered by up titration for 2 weeks, followed by 12 weeks of a stable dose, followed by 1 week of down titration. The clinical trial based its results off of a beginning measurement of a timed 25-foot walk test and measured a percent change in the original timed test and the timed test after going through one of the 3 dosing regiments of Fampridine-SR or the placebo regiment. Since the purpose of the Fampridine-SR is to increase message transmission that can be disrupted by Multiple Sclerosis examining muscle use is a very good way to examine the effects of the Fampridine-SR. One major effect of disrupted message transmission is loss of control over the musculoskeletal system so this test is designed to see if there is an increase in control and function of the musculoskeletal system. Results showed a very small 1.2% increase in the placebo group, a 7.5% median increase in the 10mg group, a 9.7% median increase in the 15mg group, and a 6.9% increase in the 20mg group. In addition there were adverse events in 4.26% of the placebo group, 0% of the 10mg group, 8.0% of the 15mg group, and 12.28% of the 20mg group. In the placebo group there was one case of a Myocardial Infarction and one case of cellulitis. These could be unrelated to the disease as the placebo was just a sugar pill, and this is not really of concern. There was a case of nausea and a case of vomiting in the 15mg Fampridine group, and there were also 2 Multiple Sclerosis episodes and 1 episode of mental disorder. The nausea and vomiting is not too concerning as such a small percent of participants experienced these symptoms, and the 2 cases of Multiple Sclerosis are also not too concerning as this is still a very low percentage of participants. The 1 case of mental disorder is also not really of concern. There were 4 cases of Multiple Sclerosis incidents in the 20mg group, as well as 1 case of convulsions, and 2 cases of seizures, and 1 kidney infection. Again, these were all pretty small percentages of the participant group so this is not really of too much concern. All of these incidents of adverse events show there could be some concern and there might be some adverse effects to this drug, but the trial did not conclude it to be a safety issue. All of the percentages of incidents were very small and none of them were specifically linked to the Fampridine-SR, so it is not considered a safety risk and should be continued to be researched into for its possible positive effects. Based on the results, the 15mg dosing regiment resulted in the biggest increase in performance in the 25-foot walk test, but the 10mg dosing regiment did not result in any adverse events, and still resulted in a pretty significant increase in performance in the test, so therefore it could be considered the most desirable dosing regiment. The results from this phase 2 trial indicate Fampridine-SR can be used to effectively treat symptoms of Multiple Sclerosis and based off the results of this study, the 10mg dosing regiment seems to be the best one to examine further.
Another phase 3 clinical trial attempted to prove Fampridine-SR is much more effective for treating Multiple Sclerosis than a placebo drug would be and allowed participants to be ages 18 to 70, to be of either gender, and required them to be diagnosed with Multiple Sclerosis.

This trial looked at improvements in a timed 25-foot walk and had an evaluator examine the improvement of each individual’s hip flexor strength, knee flexor and extensor strength, and ankle dorsiflexor strength. Like the test in the previous trial, these tests were designed to investigate improvement in muscle coordination and function, both of which generally decrease for those afflicted with Multiple Sclerosis. In the study, one group took a placebo sugar pill while the other group took 10mg of Fampridine-SR twice daily for 9 weeks. 119 participants received the 10mg of Fampridine-SR, and 118 received the placebo sugar pill. The results showed that there were 51 responders to the Fampridine-SR group, and 11 responders to the placebo group. This is very significant and indicates that Fampridine-SR could be very useful for treating symptoms of Multiple Sclerosis. The results also showed a somewhat significant difference in the evaluator tests. For the Fampridine-SR regiment, results showed a difference of .09 and the placebo group showed a difference of .04 based on the evaluator scale, which was designated to have a minimum of 0 and a maximum of 5. This shows Fampridine-SR could be effective in treating both the primary and secondary outcomes measured during this trial. There were adverse events in 5% of the Fampridine-SR participants and 3.36 % of the placebo group. This is a very insignificant difference when compared to the placebo group so there is not too much concern about these events and the results didn’t indicate there was any safety issue. The results of both of these clinical trials show that Fampridine-SR can be effective in treating symptoms of Multiple Sclerosis, specifically

helping coordination with muscles and creating movements, and that more trials should be conducted into this drug to further verify its effectiveness.