Highly Effective Gene Therapy to Treat Duchene Mus

[Andre]

Hi David,

do you know this?
It sounds very well.

Duchenne muscular dystrophy (DMD) is the most common form of the childhood muscular dystrophies, affecting 1 in
3,500 newborn males worldwide. DMD gets worse over time, and boys usually lose the ability to walk by age 12, and
generally don't survive beyond their 20s. DMD is caused by mutations in the dystrophin gene and can be treated by
gene therapy. However, the large size of the gene has been one of the major obstacles in gene therapy for DMD.
Minimized genes have been developed and used in animal studies and phase I human trial. A drawback of the current
minimized genes is that they cannot fully restore the biological function of the full-length gene. In particular, they cannot
restore nNOS, a critical signaling molecule, to the muscle membrane. Thus, they cannot provide a complete cure.
The present invention demonstrates the development of a novel synthetic mini gene accomplishing all the biological functions
of the full-length gene. This novel minigene restores muscle force and it can also restore muscle signaling by recruiting nNOS to the
muscle cell membrane.
POTENTIAL AREAS OF APPLICATIONS:
• Gene therapy for Duchenne muscular dystrophy, Becker muscular dystrophy and X-linked dilated cardiomyopathy
MAIN ADVANTAGES OF INVENTION:
• The novel mini-gene effectively recruits nNOS to the sarcolemma resulting in significant reduction in muscle disease
and could provide a complete cure for Duchenne muscular dystrophy
• The novel mini-gene’s small size allows a greater choice in delivery vectors thus reduces the risk of adverse reaction to
gene therapy.
STATE OF DEVELOPMENT:
• Vector constructs have been fabricated which can be directly used for gene therapy studies.
• Fully functional mini-gene constructs are ready for gene therapy studies.
FURTHER R&D IN PROGRESS:
• Confirmation of therapeutic advantage in transgenic mice.
• Testing the vector constructs in animal models of DMD.
LICENSING POTENTIAL:
• University actively seeking licensee/partner to commercialize the technology
PATENT STATUS:
• Application filed
INVENTOR(S):
• Dongsheng Duan, Yi Lai, Yongping Yue
CONTACT INFO:
Office of Technology Management & Industry Relations
Charlene Boyes, Sr. Licensing & Business Development Associate- Life Sciences
Email: [e-mail]
Phone: [phone]

Link: otsp.missouri.edu/PDF/07UMC002.pdf

André

[Andre]

Also from University of Missouri-Columbia,

02/04/2007 - A novel approach to gene therapy for muscular dystrophy using trans-splicing adeno-associated viral vectors

Gene therapy has great potential to treat Duchenne muscular dystrophy. Among many proposed strategies to deliver a therapeutic gene to muscle, adeno-associated virus-mediated (AAV) gene transfer is considered one of the most promising. Even though AAV is an attractive gene transfer vehicle, the small packaging capacity is a long-standing hurdle limiting its broad application in gene therapy. Dr. Ghosh Arkasubhra and his colleagues from the University of Missouri-Columbia School of Medicine have previously described an original strategy for rationally designing trans-splicing AAV (tsAAV) vectors that double the packaging capacity of an AAV vector and efficiently carry therapeutic genes. Consequently, these vectors should be able to overcome the size barrier that has limited gene therapy for Duchenne muscular dystrophy and many other inherited diseases, such as cystic fibrosis. The authors tested their strategy using a therapeutic dystrophin gene an optimized mini-dystrophin tsAAV vector in dystrophic mice and demonstrated that the same transduction efficiency could be attained as that of a single AAV vector after intramuscular injection. In this study they aimed to achieve therapeutic levels of transduction in several tissues by developing a pair of optimized reporter gene tsAAVs that expressed heat-resistant human placental alkaline phosphatase (AP). Six weeks after systemic delivery of AAV serotype 9 pseudotyped AP tsAAV vectors in newborn mice, wide-spread expression (¡Ý90%) of AP was observed throughout the skeletal musculature. Importantly, >50% of cardiomyocytes were transduced, the threshold required for treating cardiomyopathy. Furthermore, widespread transduction was also observed in the lungs and both alveolar cells and conducting airway epithelial cells. This proof-of principal study demonstrates for the first time that successful bodywide transduction using tsAAV can be achieved and opens new avenues for promising vector technology for human gene therapy.

Andr¨¦

[David Feder]

Hi Andre: I see this new. It's for the future. A good way and more effective to delivery dystrophin gene. They need money to do more studies and after this they will start trials
I see this information in trialserve:

forum.trialserve.com/forum/viewthread?thread=192

"Thank you for your interest in this University of Missouri technology.

As you are aware, only a few gene therapy trials have been conducted in humans in Europe and USA. The technology mentioned in the abstract that we have posted at the UM website (attached) is based on studies in mouse models for DMD. Our investigators have found the technology to be highly effective in the mouse model and believe it will be highly effective in humans since this novel invention will allow for recovery of all the known biological functions of the dystrophin gene. This also makes it a very promising therapeutic strategy for DMD, BMD and XLDC patients.

Currently we are seeking partners to license the technology for more extensive evaluation in animal models and also for future clinical studies.
Please let me know if I can provide any further information."