Minovia Therapeutics Reports First Clinical Data Demonstrating Disease-Modifying Efficacy and Safety of Mitochondrial Augmentation Therapy in Pediatric Patients with Primary Mitochondrial Diseases

Minovia Therapeutics reported the publication of positive results for the first clinical use of mitochondrial augmentation, the transplantation of maternal mitochondria, to treat pediatric patients with primary mitochondrial diseases.

The study, published in Science Translational Medicine, was conducted in collaboration with global leaders in the field of hematology and primary mitochondrial disease at Sheba Medical Center in Tel Hashomer, Israel. Mitochondria are organelles in the cells that are critical for producing energy to power biologic activity.

Single, large deletions in mitochondrial DNA can lead to a variety of devastating diseases, including Pearson syndrome and Kearns-Sayre syndrome. These mtDNA deletion syndromes are sporadic, uncurable. and ultimately fatal. Pearson syndrome is a bone marrow failure disease that usually begins in infancy. In addition to presenting with sideroblastic anemia, patients are characterized by exocrine pancreas dysfunction. About half of patients die in infancy or childhood, while many who survive go on to develop Kearns-Sayre syndrome, a progressive multisystem disorder.

“These findings demonstrate that mitochondrial augmentation therapy is feasible in children with mitochondrial DNA deletion syndromes and that autologous CD34+ cells augmented with mitochondria derived from maternal blood may potentially deliver some functional improvement for patients living with these debilitating diseases for which there are no available therapies,” said Elad Jacoby of the   hemato-oncology pediatric department of Sheba Medical Center.

MAT is designed to rescue mitochondrial function and metabolic activity in diseased cells through enrichment with healthy mitochondria. This builds upon Minovia’s previous demonstration that MAT provides long-term functional benefit in an immunocompromised mouse model, and that mitochondria can transfer between hematopoietic stem cells in vivo. Preclinical studies showed that hematopoietic stem and progenitor cells can transfer normal mitochondria to hematopoietic and non-hematopoietic cells and improve disease features.

Minovia is developing MAT to treat primary mitochondrial diseases such as Pearson syndrome, as well as other mitochondrially-related sideroblastic anemias. The company’s lead investigational candidate, MNV-101 (MNV-BM-BLD), has been granted the Fast-Track, Orphan Drug and Rare Pediatric Disease designations by the U.S. Food and Drug Administration.

The latest study reported results from six patients ranging from 2 to 7 years of age: four with Pearson syndrome and two with KSS spectrum. All six patients suffered from significant failure to thrive and advanced multi-organ disease, which was either immediately or potentially life-threatening, requiring multiple ongoing supportive care interventions.

No treatment-related adverse events were reported. Adverse events related to the leukapheresis procedure were managed with standard medical care. Adverse events that occurred following treatment were expected due to the patient’s underlying disease and resolved spontaneously or with appropriate treatment.

Higher levels of normal mitochondrial DNA were observed in the blood of four out of six patients, indicating a reduction of mitochondria with large DNA deletions.

Clinical improvement in aerobic function was observed in some patients, and five of six patients experienced weight gain.

Quality of life measurements showed improvement in most patients. Changes in the general well-being of children and physical activity were reported, along with increased time spent awake and in play.

A series of aerobic and endurance tests were performed on two patients. Both patients demonstrated improvement in leg muscle strength and endurance at 6 and 12 months post treatment.

One patient, who at baseline was unable to walk any distance, was able to walk 10 meters at 12 months and had improvement on the 30-second sit-to-stand test.

Another patient demonstrated improvement in muscle function in some tests and a sustained improvement in others, including the six-minute walk test and sit-to-stand capacity at 6 and 12 months.

“We are tremendously encouraged by evidence of improvement to the quality of life and well-being of the children treated with MAT, including clinical improvements in aerobic function, weight gain and increased strength and endurance,” said Natalie Yivgi Ohana, co-founder and CEO of Minovia. “We believe these findings lay important groundwork for further development of MAT and future clinical trials to demonstrate the effectiveness and safety of MAT in patients with primary mitochondrial disorders and other diseases. Our excellent collaboration with the clinicians and teams at the Sheba Medical Center, as well as with patient advocacy groups, will enable us to accelerate the clinical development plans for Pearson Syndrome patients.:

Author: Rare Daily Staff