Sodium dichloroacetate

The pyruvate dehydrogenase complex is the enzyme group that lets mitochondria turn sugar into energy. In PDC deficiency a genetic change, most often in the PDHA1 gene, leaves the complex working poorly, so pyruvate piles up and is turned into lactic acid, and the brain and muscles run short of energy. The body also has a brake on the complex, an enzyme called pyruvate dehydrogenase kinase that switches it off.

Dichloroacetate blocks that brake, so whatever working complex a child has stays switched on more of the time, more fuel reaches the mitochondria and lactate falls. The liver breaks DCA down with an enzyme made by the GSTZ1 gene, and children with some versions of that gene clear it more slowly, which is why the trial set each child's dose from a GSTZ1 test.

SL1009-01 (NCT02616484) was a Phase 3 double-blind crossover trial at 9 US sites that enrolled 34 children from June 2020 to August 2023: each child took DCA for 4 months and placebo for 4 months, in random order with a 1-month break between, and could then continue on open-label DCA^[8][7]. The main goal, a caregiver-reported motor score (ObsRO motor), was not met in the blinded comparison (P = 0.512)^[7]; the FDA's letter puts the difference at 0.29 points in favor of placebo^[6].

Plasma lactate fell by 0.48mmol/L, about 20% (P = 0.006), and the published paper reports a statistically significant motor improvement with longer treatment including the open-label extension (P = 0.002), most in children with more motor impairment at the start^[7].

A companion analysis, SL1009-02, compared survival in 28 treated children with 28 untreated children, matched by sex and age at onset, from a natural history study published in 2012: 4 deaths occurred in 39.9 person-years in the untreated group and none in 59.3 person-years among children who stayed on DCA as of July 24, 2024 (log-rank P = 0.027).

One child who stopped DCA after the blinded phase died of COVID-19 pneumonia 3 months later^[7]. The FDA concluded that the survival comparison could not show a treatment effect, because the groups differed in how age of onset was recorded, in brain scan findings, in how the disease was diagnosed and by an average of 18 years in when they were treated, and it called the post hoc motor subgroup analysis inappropriate^[6].

Saol's resubmission rests on reanalyses of the same functional, survival, mechanism and long-term safety data^[2]. The results were published in JCI Insight on September 22, 2026; the paper's authors include a Saol employee and the owner of Medosome Biotec, which may receive royalties^[7].

The main known risk of dichloroacetate is damage to the nerves of the hands and feet (peripheral neuropathy), which is usually reversible. A 2006 trial in adults and children with MELAS, a different mitochondrial disease, was stopped early after 17 of 19 people who stopped the study drug did so because of new or worsening neuropathy at 25mg/kg a day without gene-guided dosing^[10].

A 2019 review by Peter Stacpoole's University of Florida group calls this neuropathy the main dose-limiting side effect of long-term DCA^[11]. In the Phase 3 PDC deficiency trial, which used GSTZ1-guided doses, 25 of 34 children (73.5%) reported 76 adverse events while on DCA and 27 (79.4%) reported 73 on placebo; constipation, diarrhea, tiredness and muscle weakness were among those seen on DCA, no neuropathy was reported during the blinded part, and 1 case of mild neuropathy appeared after 18 months in the open-label extension^[7].

The same paper reports rises in ketones (beta-hydroxybutyrate) of up to 3mmol/L in some children on a ketogenic diet, with no ketoacidosis, and its authors suggest checking ketones in children on the diet^[7]. In an earlier long-term follow-up of 8 patients treated for 9.7 to 16.5 years, blood counts, salts, kidney and liver tests stayed stable, and nerve test changes led to a lower dose or a pause in 3^[12].

The FDA's 2025 letter also asked for a study of the drug's effect on heart rhythm (a thorough QT study) and a food effect study^[6]; Saol has not said publicly whether these were done. There is no US label yet.

Dichloroacetate has been studied as a treatment for inherited lactic acidosis for decades, led by Peter Stacpoole at the University of Florida, who started the Phase 3 trial before Saol took over as sponsor; a 2006 controlled trial in 43 children with mixed causes of congenital lactic acidosis found it lowered the rise in lactate after meals but did not improve neurological outcomes^[13][4].

Saol submitted the new drug application on November 27, 2024 and announced it on December 3, 2024, listing Orphan Drug, Fast Track and Rare Pediatric Disease designations^[4][1]. The FDA issued a complete response letter on August 27, 2025, which Saol announced on September 8, 2025; the letter said the data did not show substantial evidence of effectiveness and asked for at least 1 new adequate and well-controlled trial, and Saol said it found no manufacturing concerns^[6][3].

After a Type A meeting in December 2025 and a Type C meeting in March 2026, where Saol says the FDA advised more survival analyses, Saol resubmitted on June 30, 2026 without a new trial. The FDA accepted it as a complete Class 2 response with Priority Review and a December 30, 2026 goal date^[2][1]. Saol's releases describe 2 regulatory routes for the dosing test: its acceptance release names a 510(k) with Medosome Biotec, and earlier releases describe a Humanitarian Device Exemption application^[1][3].

Saol has not said which route the test is on now. In September 2026 Saol announced up to $115 million in milestone-based financing from funds managed by Oaktree to prepare for a launch^[5].