Mitochondrial Disease

About Mitochondrial Disease

Numerous health problems, including neurological and muscular degeneration, cardiomyopathies, cancer, diabetes, and pathologies of aging can arise from mitochondrial dysfunction. Disorders such as Leigh syndrome, MELAS, NARP Syndrome and Freidrich’s Ataxia have been associated with mitochondrial defects. Severe mitochondrial defects can result in childhood disorders such as Leigh syndrome, for which there are no effective therapies and are often fatal.

Preclinical studies showed evidence that rapamycin, through inhibition of the mTOR signaling pathway, robustly enhances survival and attenuates disease progression in a mouse model of Leigh syndrome [1]. Administration of rapamycin to these mice, which are deficient in the mitochondrial respiratory chain subunit Ndufs4, delays onset of neurological symptoms, reduces neuroinflammation, and prevents brain lesions. Rapamycin induces a metabolic shift toward amino acid catabolism and away from glycolysis, alleviating the buildup of glycolytic intermediates, which could contribute to its therapeutic benefits. This approach of could be applicable for a broad range of mitochondrial diseases.

Due to the unique pharmacological profile of ABI-009, ABI-009 is well-suited for the treatment of certain mitochondrial diseases. AADi is conducting a phase 2a study to determine the optimal dose and utility of ABI-009 in pediatric patients with Leigh syndrome.

[1] Johnson et al (2013). Science. 342 (6165): 1524–1528

Mitochondrial Disease

March, 7 2019, Aadi Bioscience, Inc. (Aadi), For the first time in his life, Shanahan “Shanny” Dameral, 19, has a girlfriend. Soon, he’ll be graduating with a high school diploma and looking for his first job on the Kitsap Peninsula. What seems routine for many is a big deal for Dameral and other children living with treatment-resistant or intractable epilepsy. For reasons largely unknown, seizures in this subset of children persist long past their discovery in early childhood despite being treated with multiple medications and undergoing surgery to remove the affected parts of their brain. Diagnosed with epilepsy at age 5, life for Dameral has always come with seizures attached. When his seizures returned after a second brain surgery shortly after his 16th birthday, his mom Linley Allen, hoped for a medical breakthrough. “We needed to find something else since another surgery was out of the question,” Allen said. “We had heard about a drug being studied for a more severe seizure condition. I kept holding onto hope that it might be expanded to treat Shanny’s type of seizures because it was all we had at the time.”   See all and the original News article here: New Drug Trial Gives Hope for Treatment-Resistant Epilepsy