Dalfampridine, known by the brand name Ampyra, is a prescription medication used to help improve the ability to walk in adults who have multiple sclerosis (MS). It is the first drug specifically approved to enhance mobility for individuals with this condition. This medication addresses some of the functional challenges that arise from the disease, offering a targeted approach to managing one of its more disruptive symptoms.
Nerve Signal Disruption in Multiple Sclerosis
Multiple sclerosis is an autoimmune disease where the body’s own immune system attacks the central nervous system. This attack targets the myelin sheath, a protective, insulating layer that covers nerve fibers, much like the plastic coating on an electrical wire. The process of myelin damage, called demyelination, leaves the underlying nerve fiber, or axon, exposed and vulnerable.
When myelin is lost, the normally smooth and rapid transmission of electrical signals along the nerve is disrupted. This damage exposes voltage-gated potassium channels that are usually covered by the myelin sheath. With these channels now uncovered, there is an excessive leakage of potassium ions out of the axon. This outflow of positive charge weakens the electrical signal, preventing it from effectively reaching its destination.
This interruption of the nerve impulse is a direct cause of many MS symptoms. For walking, which requires complex and coordinated communication between the brain, spinal cord, and leg muscles, this signal disruption can be particularly debilitating. The effect is similar to a leaky garden hose losing water pressure; the damaged nerve fails to deliver a clear and strong signal for muscle movement.
The Role of a Potassium Channel Blocker
Dalfampridine functions as a broad-spectrum potassium channel blocker. Its mechanism of action directly addresses the potassium leakage that occurs in demyelinated nerve fibers. By physically obstructing these exposed channels, dalfampridine prevents potassium ions from leaking out of the axon. This action helps to preserve the electrical charge within the nerve cell, allowing the signal to propagate more effectively along the damaged fiber.
Instead, it improves the function of nerves that have already been demyelinated. By blocking the aberrant flow of potassium, dalfampridine helps to restore a more normal pattern of nerve conduction.
Revisiting the leaky hose analogy, dalfampridine acts like patches placed over the holes, which restores water pressure. In the same way, plugging the potassium leaks in the nerve membrane helps to restore the strength and reliability of the electrical signal traveling down the axon.
Translating Cellular Action to Clinical Improvement
The restoration of nerve signal conduction translates into a clinical benefit for some individuals with MS. Clinical trials have demonstrated that dalfampridine can lead to a measurable increase in walking speed. In these studies, responders to the treatment saw their walking speed increase by an average of about 25%. This improvement was measured using the Timed 25-Foot Walk, a standard assessment in MS clinical practice.
Dalfampridine is a symptomatic therapy, meaning it addresses the symptoms of MS rather than the disease itself. It does not modify the long-term course of MS, prevent relapses, or repair damaged myelin. The benefits of the medication are only present while it is being actively taken; if the drug is stopped, the improvements in walking are lost.
Not everyone with MS will experience this benefit. Clinical studies showed that approximately one-third of patients treated with dalfampridine experienced a clear improvement in walking speed. For those who do respond, the improvement can be meaningful, as reflected in patient-reported outcomes that show a reduction in self-assessed walking disability.
How the Body Manages Dalfampridine
Dalfampridine is formulated as an extended-release tablet to ensure its effects are consistent. This formulation allows the drug to be absorbed slowly from the gastrointestinal tract, which prevents sharp spikes in its concentration in the bloodstream. Maintaining a steady level of the medication is important for effectiveness and for safety, as higher peak concentrations are associated with an increased risk of adverse effects, including seizures.
Once absorbed, dalfampridine is almost entirely eliminated from the body through the kidneys, with about 90% of the drug excreted unchanged in the urine. Because of this reliance on renal clearance, kidney function is a significant consideration. The drug is contraindicated for individuals with moderate to severe kidney impairment because reduced kidney function can lead to the drug accumulating to unsafe levels. Physicians assess a patient’s creatinine clearance, a measure of kidney function, before prescribing dalfampridine.