This study intends to study the safety and tolerance of the combination of pyruvate, creatine, and niacinamide over 6 months in patients with PSP.

There are no effective symptomatic or biologic treatments for progressive supranuclear palsy (PSP), a relatively rare neurodegenerative disease that presents late in life with relentless progressive postural balance disturbances, non-levodopa responsive parkinsonism, supranuclear vertical gaze palsy, pseudobulbar palsy, and frontal behavioral and dysexecutive symptoms. In light of currently proposed etiopathogenic mechanisms in PSP and based on successful experiments inhibiting cellular neurotoxicity, it is hypothesized that preservation of brain energy homeostasis may allow endogenous neuroprotective mechanisms to reverse or impede free radical injury or other neurotoxic events leading to neurodegeneration in this disease. An emerging literature has described the neuroprotective effects of pyruvate, (as a neuronal energy fuel and free radical scavenger); niacinamide, (which boosts cofactor NAD), and creatine, (which buffers and selectively parcels cellular energy utilization) in various animal models of brain injury or degeneration.

Ajay Verma et al. have further demonstrated a synergistic neuroprotective effect of these three nutrients in various neural injury models. We thus propose using these nutrients as a novel and safe neuroprotective approach for treating PSP patients. This randomized, double-blind, placebo, control pilot study will test the safety and tolerance of this nutrient combination over 6 months in patients with PSP, and will measure their transport across the blood brain barrier. In addition to clinical and neuropsychological outcome measures, brain creatine will also be evaluated using magnetic resonance spectroscopy before and after therapy

Inclusion Criteria:

• All subjects must meet the clinically definite or probable NINDS-SPSP PSP diagnostic research criteria that includes the presence of postural instability at disease onset, as well as supranuclear vertical ophthalmoparesis.
• All subjects must be able to tolerate oral feedings and be ambulatory
• All subjects or their caregivers must be able to read and understand the consent

Exclusion Criteria:

• Any contraindications to the use of pyruvate, creatine, and niacinamide
• the presence of a medical condition that can reasonably be expected to subject the patient to unwarranted risk or require frequent changes in medication.
• Pregnancy, nursing, or lack of effective contraception, if still at child-bearing age.
• History of prior sever traumatic brain injury or other severe neurologic or psychiatric condition, such as psychosis, stroke, multiple sclerosis, or spinal cord injury, which will interfere with outcome evaluation, in the opinion of the local principal investigator
• Subject unable to discontinue prohibited medication, which includes antiparkinsonian medications with potential neuroprotective effects such as amantadine, deprenyl, and vitamin E supplements > 400 IU per day.