Department Chair Professor Catherine Clarke has been awarded a $100,000 Barth Syndrome Foundation (BSF) research grant to study lipid replacement therapy.
Clarke will receive the grant over a two-year period for her the project titled “Deuterated polyunsaturated fatty acids as a protective therapy in the treatment of Barth syndrome.”
Barth syndrome (BTHS) is a rare but serious, X-linked genetic disorder of lipid metabolism primarily affecting males. The condition is characterized by an enlarged and weakened heart (dilated cardiomyopathy), weakness in muscles used for movement (skeletal myopathy), recurrent infections due to small numbers of white blood cells (neutropenia), and short stature.
According to the Barth Syndrome Foundation’s (BSF) announcement about the 2018 research grants, the discovery of viable therapies to alleviate suffering and prolong life for individuals affected by Barth syndrome is the impetus behind the therapeutic research strategy employed by BSF. To that end, the research grant recipients demonstrated innovative and scientifically-rigorous approaches to addressing knowledge gaps in three key areas: gene therapies, modification of cardiolipin, and improving mitochondrial function. Clarke’s grant is made possible by support from the Will McCurdy Fund for Advancement in Therapies for Barth Syndrome.
BTHS is uniquely associated with a deficiency and alterations in cardiolipin, a phospholipid that is an important component of the inner mitochondrial membrane. This deficiency and alterations in cardiolipin result in damage to the cell. Providing a “disease-resistant” cardiolipin to increase and replace the usual molecules may be therapeutic for individuals with Barth syndrome. Image at right:
The cardiolipin molecule which has four fatty acid chains is altered in Barth syndrome. (Catherine Clarke/UCLA)
Clarke and her team will test the hypothesis by applying this unique therapeutic idea by using chemically modified lipids to reduce the amount of cellular damage produced by deficient and altered cardiolipin. If this novel specific lipid-replacement therapy preserves mitochondrial function, it could protect cells against the oxidative stress conditions known to exist in people with Barth syndrome.
Clarke earned her B.S. and Ph.D. in biochemistry at UCLA and, afterwards, conducted postdoctoral research at Princeton University. She has been a UCLA faculty member in the department since 1993, and a full professor since 2002. In 2016, Clarke was appointed as the first female Chair of the Department of Chemistry & Biochemistry. She is a recipient of the Ellison Medical Foundation Senior Scholar Award and the Hanson-Dow Award for Teaching Excellence.
Clarke conducts research on coenzyme Q, an essential lipid component in cellular energy metabolism. She employs a combination of molecular genetics, biochemistry, and lipid chemistry to delineate the biosynthetic steps responsible for the production of Q, as well as to investigate its function as an antioxidant. Her research team identified nine out of the 11 coenzyme Q polypeptides needed for Q biosynthesis, and showed they form a multi-subunit biosynthetic complex or CoQ-synthome. Her research may produce a better understanding of how coenzyme Q can be modulated for optimal health. Learn more about Clarke’s research at her website.
Penny Jennings/UCLA Department of Chemistry & Biochemistry, penny@chem.ucla.edu.
