Canine Muscular Dystrophy Frequently Asked Questions

Q: What is Duchenne muscular dystrophy?

A: Duchenne muscular dystrophy (DMD) is a genetic disorder affecting approximately one in every 7,250 males between the ages of 5 and 24, according to Centers for Disease Control and Prevention statistics. It is caused by a mutation in a gene called dystrophin, which helps keep muscle cells intact. DMD causes the muscles to weaken, and boys with DMD often have trouble walking and eventually become wheelchair-bound. Over time, other muscles, such as those in the heart and diaphragm, also weaken, and patients become prone to cardiomyopathy, serious respiratory infection, and pneumonia.

Q: Are there any cures or treatments for DMD?

A: There is currently no cure for DMD nor are there any therapies that treat the cause of the disease or that reverse the symptoms. Corticosteroid drugs can sometimes slow the course of DMD, but they can also have severe side effects and are not recommended for long-term use. In September 2016, a drug called Eteplirsen was approved by the FDA that may treat DMD at its source, by increasing production of dystrophin. However, its approval was controversial. Outside experts, FDA advisory groups, and FDA top level officials did not recommend its approval, and human clinical trials are still underway.

Q: Why are dogs used in DMD research?

A: Like humans, some breeds of dogs, including golden retrievers, Welsh corgis, Cavalier King Charles spaniels, German shorthaired pointers, and Labrador retrievers, can also carry a genetic mutation in the dystrophin gene, resulting in some symptoms similar to those in human DMD. In addition, dogs’ size is similar to that of young boys and their life span is longer than that of smaller animals, such as mice. However, this disease is naturally very rare in dogs, and scientists must continuously breed them to carry the mutation in order to provide enough dogs with DMD to conduct their experiments.

Q: What happens to dogs in DMD research?

A: Dogs bred for DMD research suffer greatly. Puppies with this disease are not able to suckle and must be fed with a syringe just to survive their first few weeks of life. By the time they are 8 weeks old, their muscles have stiffened, making it difficult for them to walk normally, and they have difficulty opening their jaws. Puppies in DMD research can’t run, jump, or play like normal puppies. As they age, their muscles waste away, their legs become misshapen, and their spines begin to curve inward, and it becomes even more difficult for them to get around with such restricted movement. The muscles in their tongues enlarge, making it impossible to eat or swallow food normally and causing excessive drooling. The fur around their mouths is constantly wet with saliva containing food and bacteria, putting them at risk for skin infection. Because of the difficulty with eating and the enlargement of their diaphragm muscles, dogs in DMD research often develop severe and fatal respiratory problems; 50 percent die from these problems before 15 months of age. Those that survive often go on to develop congestive heart failure. It is because of this severe suffering that veterinarians have long recommended against breeding dogs with this condition. Yet, colonies of dogs with DMD are maintained at institutions around the world, including at Texas A&M, the University of North Carolina at Chapel Hill, the University of Missouri at Columbia, and the Alfort National Veterinary School in France. The U.S. taxpayersupported National Institutes of Health has provided much of the funding for these breeding programs.

Q: What are the problems with using dogs in DMD research?

A: While there are some similarities between DMD in humans and dogs, there are also important differences. For example, 20 to 30 percent of affected puppies die as a result of diaphragm failure, which doesn’t occur in human infants with DMD. On the other hand, human patients often experience growth retardation and learning disabilities, neither of which has been observed in dogs with DMD. Since DMD is a disease of the muscles, it is also important to recognize that in four-legged animals such as dogs, muscles have different composition, energy use, and functions than they do in two-legged humans. There are also differences in life span; humans with DMD live approximately one-third of their normal lifespan, while dogs can live up to one-half of their normal lifespan.

Q: Have experiments using dogs helped humans suffering from DMD?

A: No. It has been widely acknowledged that the results obtained from dog MD experiments have not translated into effective treatments to cure or reverse the disease in human children. This failure has been attributed to major differences in physiology between dogs and humans, differences in disease progression, and the way animal studies have been conducted. Unfortunately, some experiments have even led scientists in the wrong direction, as certain treatments have generated results that were the opposite of results in humans.

Q: Are other animals used in DMD research?

A: Yes. The most commonly used animal in DMD research is the mouse. Experimenters have genetically modified and bred at least 60 different strains of mice for DMD experiments, most of which are different forms of the most commonly used mdx mouse. Mdx mice also don’t possess dystrophin, but the differences between mice and humans are even greater than the differences between dogs and humans. In fact, mdx mice show almost no clinical symptoms. Other species that have been used for DMD experiments include pigs, cats, rats, zebrafish, flies, and roundworms.

Q: Are there alternatives to using animals in DMD research?

A: Yes! Modern biotechnology is rapidly advancing DMD research. For example, scientists have recently used sophisticated technology to restore dystrophin function in human cells obtained from actual DMD patients, a discovery that may result in treatment for up to 60 percent of the DMD population. Researchers are finding ways to grow functional human muscle tissue so that it might be transplanted into DMD patients to restore muscle function or be used to screen potential new drugs. In addition, Harvard scientists recently engineered a human DMD “tongue-on-a-chip” that uses muscle stem cells from DMD patients to recreate human muscle tissue on thin, microfluidic devices. Using this model, the scientists were partly able to explain why muscle regeneration fails in these patients and leads to profound muscle weakness.

References

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Chal J, et al. Generation of human muscle fibers and satellite-like cells from human pluripotent stem cells in vitro. Nat Protoc. 2016;11:1833-1850.

Dunayer E. Scientific problems with animal models of Duchenne muscular dystrophy. Perspectives on Medical Research. 1991;3.

Kornegay JN, et al. Canine models of Duchenne muscular dystrophy and their use in therapeutic strategies. Mamm Genome. 2012;23.0:85-108.

Kornegay JN, et al. Golden retriever muscular dystrophy (GRMD): developing and maintaining a colony and physiological functional measurements. Methods Mol Biol. 2011;709:105-123.

McGreevy JW, et al. Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy. Dis Model Mech. 2015;8.3:195-213.

Nesmith AP, et al. A human in vitro model of Duchenne muscular dystrophy muscle formation and contractility. J Cell Biol. 2016;215.1: 47-56.

Young CS, et al. A single CRISPR-Cas9 deletion strategy that targets the majority of DMD patients restores dystrophin function in hiPSC-derived muscle cells. Cell Stem Cell. 2016;18.4:533-540.