To evaluate the effects of RT001 in 3 subjects with PSP.

Lipid peroxidation (LPO) is a free-radical chain reaction that liberates toxic reactive aldehydes.  These aldehydes modify tau protein in PSP, preventing clearance.  Defective mitochondrial oxidative phosphorylation and toxic LPO byproducts are increased in PSP patients.  RT001 is a deuterium-stabilized linoleic acid (D2-LA) that is readily incorporated into membranes, preventing formation of these aldehydes and oxidative damage.

Measurement of PK, the PSP Rating Scale (PSP-RS) and Unified Parkinson’s Disease Rating Scale (UPDRS) were made at baseline and every 3 months for 12 months.  RT001 was dosed orally at 2.88 g BID.   

During the 12-month treatment period, scores diverged from disease progression predicted by large natural history studies of PSP.  Slope of the PSP-RS changed from the historical +0.91 points/month to a mean of +0.04 points/month (+/- 0.11) indicating a halting of progression.  The UPDRS slope changed from an expected +0.95 points/month to an average -0.79 points/month (+/-0.005), indicating a potential reversal of progression.  Mean plasma and RBC membrane levels of drug were 21% and 19% of total linoleic acid. Levels of di-deuterated arachidonic acid (D2-AA) in both plasma and RBC also increased, indicating normal enzymatic processing of the stabilized LA into stabilized AA.

Patients and caregivers reported symptom improvements that correlated with score improvements.  No adverse events or toxicities were observed during the treatment.

Early signs of RT001 efficacy have been observed in all 3 subjects.The mean PSP-RS and UPDRS scores showed consistent and steady improvement during 12 months of treatment, against a well-studied natural history.

 RT001 (D2-LA) is absorbed and elongated into D2-AA.Within 1 month, D2-LA and D2-AA achieve plasma and RBC membrane levels sufficient to block LPO.

 RT001 was well tolerated with no toxicities reported.