How does dietary restriction produce protective effects against aging |
Starvation may protect organism against chemotherapy |
Benefits of Caloric Restriction on Memory Shown in Humans |
Cutting Calories in Middle Age Could Extend Lifespan |
Vitamin Supplement with Folic Acid good for women |
New U.S. Dietary Guidelines: Eat Less, Exercise More |
GENE THERAPY
Sci Transl Med 11 November 2009: Vol. 1, Issue 6, p. 6ra15
Research Article Follistatin Gene Delivery Enhances Muscle Growth and Strength in Nonhuman Primates.
Janaiah Kota1, Chalonda R. Handy1,2, Amanda M. Haidet1,2, Chrystal L. Montgomery1, Amy Eagle1, Louise R. Rodino-Klapac1, Danielle Tucker1, Christopher J. Shilling1, Walter R. Therlfall3, Christopher M. Walker1,2, Steven E. Weisbrode3, Paul M. L. Janssen2, K. Reed Clark1,2, Zarife Sahenk1,2, Jerry R. Mendell1,2,* and Brian K. Kaspar1,2,* +
Author Affiliations 1Center for Gene Therapy, Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA. 2College of Medicine, Ohio State University, Columbus, OH 43210, USA. 3College of Veterinary Medicine, Ohio State University, Columbus, OH 43210, USA.
Abstract Antagonists of myostatin, a blood-borne negative regulator of muscle growth produced in muscle cells, have shown considerable promise for enhancing muscle mass and strength in rodent studies and could serve as potential therapeutic agents for human muscle diseases. One of the most potent of these agents, follistatin, is both safe and effective in mice, but similar tests have not been performed in nonhuman primates. To assess this important criterion for clinical translation, we tested an alternatively spliced form of human follistatin that affects skeletal muscle but that has only minimal effects on nonmuscle cells. When injected into the quadriceps of cynomolgus macaque monkeys, a follistatin isoform expressed from an adeno-associated virus serotype 1 vector, AAV1-FS344, induced pronounced and durable increases in muscle size and strength. Long-term expression of the transgene did not produce any abnormal changes in the morphology or function of key organs, indicating the safety of gene delivery by intramuscular injection of an AAV1 vector. Our results, together with the findings in mice, suggest that therapy with AAV1-FS344 may improve muscle mass and function in patients with certain degenerative muscle disorders. Footnotes Received April 22, 2009. Accepted October 19, 2009.
Sci Transl Med 11 November 2009: Vol. 1, Issue 6, p. 6ra15
Research Article Follistatin Gene Delivery Enhances Muscle Growth and Strength in Nonhuman Primates.
Janaiah Kota1, Chalonda R. Handy1,2, Amanda M. Haidet1,2, Chrystal L. Montgomery1, Amy Eagle1, Louise R. Rodino-Klapac1, Danielle Tucker1, Christopher J. Shilling1, Walter R. Therlfall3, Christopher M. Walker1,2, Steven E. Weisbrode3, Paul M. L. Janssen2, K. Reed Clark1,2, Zarife Sahenk1,2, Jerry R. Mendell1,2,* and Brian K. Kaspar1,2,* +
Author Affiliations 1Center for Gene Therapy, Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA. 2College of Medicine, Ohio State University, Columbus, OH 43210, USA. 3College of Veterinary Medicine, Ohio State University, Columbus, OH 43210, USA.
Abstract Antagonists of myostatin, a blood-borne negative regulator of muscle growth produced in muscle cells, have shown considerable promise for enhancing muscle mass and strength in rodent studies and could serve as potential therapeutic agents for human muscle diseases. One of the most potent of these agents, follistatin, is both safe and effective in mice, but similar tests have not been performed in nonhuman primates. To assess this important criterion for clinical translation, we tested an alternatively spliced form of human follistatin that affects skeletal muscle but that has only minimal effects on nonmuscle cells. When injected into the quadriceps of cynomolgus macaque monkeys, a follistatin isoform expressed from an adeno-associated virus serotype 1 vector, AAV1-FS344, induced pronounced and durable increases in muscle size and strength. Long-term expression of the transgene did not produce any abnormal changes in the morphology or function of key organs, indicating the safety of gene delivery by intramuscular injection of an AAV1 vector. Our results, together with the findings in mice, suggest that therapy with AAV1-FS344 may improve muscle mass and function in patients with certain degenerative muscle disorders. Footnotes Received April 22, 2009. Accepted October 19, 2009.