A new gene therapy has been shown to protect mice from a life-threatening heart condition caused by muscular dystrophy. About one in 3,500 children, mostly boys, are born with Duchenne muscular dystrophy (DMD). They experience a progressive wasting away of muscles, starting in the legs and pelvis. Children with DMD have difficulty walking, and most need wheelchairs by age 12.
A new gene therapy developed by researchers at the University of Missouri School of Medicine has shown to protect mice from a life-threatening heart condition caused by muscular dystrophy.
"This is a new therapeutic avenue," said Yi Lai, PhD, the leading author of the study and assistant research professor in the MU School of Medicine's Department of Molecular Microbiology and Immunology. "This is just a first step, but we hope this could lead to a treatment for people with this devastating heart condition, which is a leading cause of death for people with Duchenne muscular dystrophy."
About one in 3,500 children, mostly boys, are born with Duchenne muscular dystrophy (DMD). They experience a progressive wasting away of muscles, starting in the legs and pelvis. Children with DMD have difficulty walking, and most need wheelchairs by age 12.
As DMD depletes the skeletal muscles, it also causes the heart to decay. A weakened heart kills up to 40 percent of people with DMD, usually by their 20s or early 30s. DMD originates with mutations in a single gene. For more than two decades, researchers have explored using gene therapy, an experimental treatment, to replace the flawed gene with a healthy copy.
The recent MU study, however, did not try to replace the faulty gene. The researchers targeted a different gene -- one involved with the heart's built-in system for responding to heart attacks and other emergencies.
This targeted gene expresses a protein called nNOS. During short-term stresses, nNOS activates briefly to help regulate the heart. The MU researchers altered the gene to enable more efficient transfer of the nNOS gene to mouse hearts.
Seven months after the gene therapy, the mice who received the treatment showed significantly improved overall heart health. On most disease indicators, the researchers found that the treatment protected their hearts from the damage of DMD.
"The study showed for the first time that a modified nNOS gene could be delivered through gene therapy to protect the hearts of mice from Duchenne muscular dystrophy," said Dongsheng Duan, PhD, co-author of the study and Margaret Proctor Mulligan Professor in Medical Research at the MU School of Medicine.
"Since nNOS protects against multiple heart diseases, this method could one day be extended to the treatment of other heart diseases, such as heart failure or a heart attack," Duan said.
The technique is in an early stage of development and will require more research before potential applications in humans are explored.
The above story is based on materials provided by University of Missouri-Columbia.Note: Materials may be edited for content and length.
1. Y. Lai, J. Zhao, Y. Yue, N. B. Wasala, D. Duan. Partial restoration of cardiac function with PDZ nNOS in aged mdx model of Duchenne cardiomyopathy.Human Molecular Genetics, 2014; 23 (12): 3189 DOI: 10.1093/hmg/ddu029
GsMTx-4 Addresses Calcium Level Imbalance – a Critical Area of Need in DMD
Akashi Therapeutics Inc., a clinical stage biopharmaceutical company developing treatments for Duchenne muscular dystrophy (DMD),announced today that it has acquired global rights to GsMTx-4, a peptide developed by Tonus Therapeutics to address calcium level imbalance in muscle, a critical issue in DMD contributing to loss of function and other associated pathologies. Originally discovered in tarantula venom by researchers at the State University of New York at Buffalo, GsMTx-4 has been shown to positively affect cellular calcium homeostasis in preclinical DMD model studies generated by Tonus.
Under the terms of the agreement, Akashi Therapeutics will acquire global rights to the compound, including intellectual property and commercialization rights,and will be responsible for all ongoing development costs. Tonus will be eligible to receive potential milestones and royalties on future sales of any resulting DMD products. No further terms were disclosed.
“Loss of calcium homeostasis, in particular increased calcium influx through stretch-activated channels,in muscle cells of DMD boys is a key initiating process of DMD pathology leading to muscle degeneration and muscle function loss,” said Professor Urs Ruegg, Ph.D., Department of Pharmacology at the University of Geneva. “We know that limiting calcium influx has the potential to slow disease progression. As GsMTx-4 is a blocker of stretch-activated channels, it has the potential to help restore this homeostasis through modulation of these channels.”
“Calcium level imbalance and associated muscle function loss is a critical problem facing children with DMD and an area that is not being fully addressed by other DMD therapies in development,” said Marc B. Blaustein, CEO of Akashi Therapeutics. “Our mission at Akashi Therapeutics is to develop a portfolio of treatments for Duchenne muscular dystrophy. We are pleased to add GsMTx-4 to our growing pipeline, which includes HT-100, our most advanced drug candidate, currently being evaluated in patients with DMD in phase 1a/2b clinical studies, and DT-200, a clinical-stage selective androgen receptor modulator.”
Preliminary Clinical Data from Ongoing Phase 1b/2a Clinical Program Presented at New Directions in Biology and Disease of Skeletal Muscle 6th Biennial Conference Cambridge, Mass.—July 3, 2014—Akashi Therapeutics, Inc., a...