Use of Dalfampridine in Primary Lateral Sclerosis

Inclusion criteria

• Male or female, aged 18-99;
• Diagnosis of upper motor neuron disease, compatible with PLS but may include upper motor neuron (UMN) predominant ALS, defined as only upper motor neuron (UMN) features in at least 2 body regions on examination.
• EMG within 3 months of enrollment with minimal or no evidence of lower motor neuron disease,
• Time from symptom onset > 18 months
• No previous allergy to dalfampridine
• No current or exposure to any therapeutic agent targeting PLS or ALS within 30 days of enrollment.
• Must have a forced vital capacity (FVC) ≥ 60% of expected
• Written informed consent prior to screening is present.
• Subjects on a stable dose of or have not taken Riluzole for at least thirty days
• Impaired walking as measured by a Hauser Index of greater than 1 and less than 7 (2 to 6, inclusive);
• Mini Mental Status Score > 22 and deemed by the PI of being capable of providing informed consent and following trial procedures.
• Geographically accessible to the site.
• Women must not be able to become pregnant (e.g., post-menopausal, surgically sterile, or using adequate birth control methods) for the duration of the study and three months after study completion. Adequate contraception includes: abstinence, hormonal contraception (oral contraception, implanted contraception, injected contraception or other hormonal contraception, for example patch or contraceptive ring), intrauterine device (IUD) in place for ≥ 3 months, barrier method in conjunction with spermicide, or another adequate method.

Exclusion criteria

• History of clinically significant liver disease, renal disease, peripheral neuropathy, serious peripheral vascular disease, known HSP or + C9orf72 or SPG4 mutation, or any other medical condition felt to be exclusionary by the investigator;
• Unwillingness to sign informed consent or any other reasons for which the investigator feels the subject cannot complete the study;
• Women who are pregnant, breastfeeding, or trying to become pregnant;
• Active cancer within the previous 2 years, except treated basal cell carcinoma of the skin;
• Subjects taking any other experimental drugs within 30 days prior to enrollment;
• Patient has any history of seizures; brain surgery, brain implants, any metallic implants above the neck, cardiac pacemakers, cochlear implants, piercing or body modification above the neck, known history of TMS related complications or side-effects, tinnitus.
• Patient has moderate or severe renal impairment as defined by a calculated creatinine clearance of ≤50 mL/minute;
• Patient has been administered botulinum toxin in the lower extremities within 6 months prior to the screening visit and/or is expected to receive botulinum toxin in the lower extremities during the course of the study;
• Patient has a known allergy to pyridine-containing substances or any of the inactive ingredients of the dalfampridine tablet (colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide);
• Patient has a history of drug or alcohol abuse within the past year;
• Patient has clinically significant abnormal laboratory values.
• Anything else that, in the opinion of the SI, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study.