Administration of MELPIDA to Determine the Safety and Efficacy for Patients With Spastic Paraplegia Type 50

collection of occurrence and severity of serious adverse events. Incidence of serious adverse events and adverse events throughout the study, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Higher grade values indicated greater severity. Grade 1 - Grade 5.

Nerve conduction studies will be used to determine nerve conduction velocity. Nerve conduction studies involve providing a small electrical stimulus to either a motor or sensor nerve and then measuring the resulting action potential at distal point of that nerve (for sensory nerve studies) or at the muscle that the nerve innervates (motor nerve studies). Velocity of conduction (measured between the two points and represented in m/s) will be obtained. The value is compared to standard reference values for age.

Changes in Liver Ultrasound findings from baseline. Incidence of serious adverse events and adverse events throughout the study, as assessed by CTCAE v5.0

Liver laboratory test: alanine transaminase (ALT) in U/L

Liver laboratory test: aspartate aminotransferase (AST) in U/L

Liver laboratory test: Total bilirubins in umol/L

Liver laboratory test: direct bilirubins in umol/L

Liver laboratory test: alkaline phosphatase (ALP) in U/L

Liver laboratory test: gamma-glutamyl transferase (GGT) in U/L

Nerve conduction study will be done to assess nerve conduction amplitude. Nerve conduction studies involve providing a small electrical stimulus to either a motor or sensor nerve and then measuring the resulting action potential at distal point of that nerve (for sensory nerve studies) or at the muscle that the nerve innervates (motor nerve studies). Amplitude of the action potential (measured at the distal site and represented in uV for sensory amplitudes and mV for motor amplitudes) will be obtained. The value is compared to standard reference values for age.

Modified Ashworth scale (0-4). 0: no increase in muscle tone; 1: slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension; 1+: slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the range of motion; 2: more marked increase in muscle tone through most of the range of motion, but affected part(s) easily moved; 3: considerable increase in muscle tone, passive movement difficult; 4: affected part(s) rigid in flexion or extension. Values reported separately for right and left upper and lower limbs.

Tardieu scale (0-5). 0: no resistance throughout passive movement; 1: slight resistance throughout with no clear catch at a precise angle; 2: clear catch at a precise angle, followed by release; 3: fatiguable clonus (<10 seconds) occurring at a precise angle; 4: unfatiguable clonus (>10 seconds) occurring at a precise angle; 5: joint immobile. Values reported separately for right and left upper and lower limbs.

Bayley 4 (Fine Motor, Gross Motor, Cognitive & Language). Scores are aggregated for each domain into a scaled score. The highest possible score on a subtest or subdomain is 19, and the lowest possible score is 1. Scores from 8 to 12 are considered average.

Number of seizures per day (numerical value)

Type of seizures, if applicable

Seizure triggers, if applicable.

Trigger will be defined by any observer or the participant. An open answer format will be collected.

Seizure rescue medication used, if applicable

Clinical Global Impression of Overall Change by Physician (1-7); 1: very much improved to 7: very much worse. Single value reported.

Vineland (Comprehensive Parent/Caregiver Form). The domain scores are expressed as standard scores with a mean of 100 and standard deviation of 15; domains: communication, daily living skills, socialization and motor skills.

Number of falls per day

Causes of any falls reported, as applicable

Clinical Severity of Illness by Physician (1-7); 1: normal, shows no sign of illness to 7: among the most extremely ill of patients. Single value reported.