Clinical Benefit and Improvement of Mitochondrial Function in Low Risk Myelodysplastic Syndrome Treated By Combination Ultra Coenzyme Q10 and L-Carnitine

Background: Structural mitochondrial abnormalities as well as alterations in gene expression of key mitochondrial proteins are well recognized in myelodysplastic syndrome (MDS), suggesting that mitochondrial dysfunction is important in the pathogenesis of this disease. Both Coenzyme Q10 and L- carnitine play an essential role in efficient cellular energy production. Clinical and cytogenetic response to high dose of Coenzyme Q10 in patients with MDS was demonstrated previously. The combination of L- carnitine and Coenzyme Q10 has shown a beneficial effect in other mitochondrial disorders. Aim: To assess the effect of combination of food supplements on the clinical course and mitochondrial function of peripheral blood cells obtained from patients with in low/intermediate- 1 risk MDS.Materials and Methods: Ultra-coenzyme Q10 (180 mg/day), L-carnitine (2000 mg/day) and a vitamin mineral complex were administered for 6 months; patients were allowed to continue treatment for an additional 6 months, if it was beneficial. Inclusion criteria were Hb<10.5g/dL or PLT<100x10⁹/L or ANC<0.8X10⁹/L. As of May 2017, 33 pts. have been enrolled in the study. Peripheral blood cells were assessed by the Seahorse XF analyzer which is a state- of- the- art tool for assessment of real time cellular respiration, by continuous measurement of Oxygen Consumption Rate (OCR) under different conditions in-vitro . Mitochondrial function assessment was performed at baseline and at six-month point. Results: The median age of the entire cohort was 75 years (range: 56-93), 20(61%) of pts. were male. Pts. were classified per IPSS-R: very low risk 7 (21%), low risk 21(64%),int. 5 (15%). Median Hb was 9.5 g/dL (6.4-12.2); 17 (52%) were transfusions dependent and 16(48%) failed treatment with erythropoietin stimulating agents (ESA). 28 patients completed treatment protocol. Six pts. (21.4%) showed a hematological Improvement according to IWG 2006 criteria (out of which 4 were transfusions dependent). Median time to the initial response was 9 weeks (5-24). At 3 months' time point 14 of 18 patients had an increased in their integral Quality of life (QOL) score per FACT questionnaire; mean improvement was 14.3 points per patient (p=0.011). The pre-treatment mitochondrial basal respiration and especially spare respiratory capacity tested on cells of 11 MDS cases were uniformly lower in comparison with healthy controls (p=0.04 and p=0.007,respectively). There was significant improvement of basal, as well as spare respiration in peripheral blood cells obtained from MDS patients after six months food supplements (p=0.0027 and p=0.02, respectively). Conclusions: We demonstrated for the first time that mitochondrial energy production in peripheral blood is impaired in patients with MDS. Furthermore, we showed that this is at least partially reversible with food supplementations known to augment mitochondrial function. Combination of Ultra coenzyme Q10 with L-carnitine and vitamin mineral complex leads to moderate clinical response in low/intermediate-1 risk MDS patients and improve QOL