Myofibrillar Myopathy in Horses: History, Feeding, and Management

Researchers identified myofibrillar myopathy (MFM) in horses several years ago. Prior to the discovery and description of MFM, veterinarians diagnosed horses exhibiting signs of MFM with polysaccharide storage myopathy (PSSM) or other medical conditions. To understand MFM and the management of the condition, it is helpful to understand how it differs from PSSM.

PSSM was originally identified by finding an accumulation of abnormal glycogen (sugar form stored in muscle) in horses of several different breeds. In 2008, a genetic mutation was found in many, but not all, horses with PSSM. Because of this, cases were divided into PSSM1 for horses with the mutation and PSSM2 for horses without the mutation but some abnormal sugar in muscle samples. Stephanie Valberg, D.V.M., Ph.D., one of the leading experts in equine myopathies, and her research group began investigating PSSM2 using a breed-specific approach.

In Quarter Horses, PSSM2 is characterized by tying-up, evidence of muscle damage (high creatine kinase [CK] in blood tests), and very high concentrations of muscle glycogen. These horses are managed like PSSM1 horses.

In a study from 2016, Valberg and her colleagues measured the amount of glycogen in muscle from Arabian horses previously diagnosed with PSSM2.^* They found that the total concentration of glycogen did not differ from healthy Arabians. What they did find was areas with disorganized contractile proteins and abnormal clumps of a protein called desmin that should organize the contractile proteins. Desmin can be readily damaged by oxidative stress. An in-depth analysis found that the horses likely developed muscle damage at the end of endurance after metabolizing large amounts of fat during exercise. Muscle damage seemed to result from an absence of a specific cysteine-based antioxidant and could be seen microscopically by visualizing clumps of desmin. Because of the misalignment of contractile proteins, PSSM2 in this breed was renamed myofibrillar myopathy or MFM.

Warmblood horses with PSSM2 were also investigated. Different from Arabian horses, the symptoms of PSSM2 included a reluctance to work and engage the hindquarters after very little exercise. In 2017, Dr. Valberg and colleagues published a study that described the newly defined myofibrillar myopathy in Warmbloods.^** Horses were initially diagnosed with PSSM2 because scattered muscle fibers had small clumps of glycogen in their cells detected in a periodic acid Schiff’s (PAS) stain. When the amount of glycogen was measured, though, it was not higher than healthy Warmbloods.  The Warmbloods were diagnosed with MFM because they exhibited abnormal aggregates of the protein desmin, which normally functions to maintain an orderly alignment of myofibrils in muscle. Detailed analysis of muscle from horses with MFM showed that, like Arabians, Warmbloods with MFM may lack a specific cysteine-based antioxidant. But, unlike Arabians, they also had evidence of a maladapted training response to conditioning programs that seemed to cause muscle pain without increasing CK in blood tests.

A diagnosis of MFM is made using a special stain on a biopsy sample that can reveal abnormal clumps of desmin. Desmin clumps develop over an extended period of time. In some situations, particularly in younger horses exhibiting signs characteristic of MFM, a muscle biopsy may not be conclusive. It is suspected in these situations that the onset of the disease may be too early for desmin aggregates to have formed, and management of the horse according to current recommendations for MFM is usually suggested.

The typical presentation of MFM in Warmbloods is often a gradual process. According to Valberg, “affected horses often have a normal training response initially, but gradually develop exercise intolerance by six to eight years of age. They show a lack of stamina, unwillingness to go forward, inability to collect, abnormal canter transitions, and inability to sustain a normal canter. MFM horses may also show unresolved hindlimb lameness, stiffness, muscle pain, and rarely an episode of exertional rhabdomyolysis with high serum CK. In most MFM horses, serum CK and AST activities are within normal limits.”

MFM is most commonly diagnosed in Warmbloods and Arabians. However, if horses of other breeds are experiencing this type of oxidative stress, they may also have some clumping of desmin in their muscle. Some horses diagnosed with MFM can have evidence of a higher amount of glycogen in their muscle biopsy based on the PAS stain. These horses are classified as PSSM2/MFM because the amount of starch and sugar provided to these horses in the diet should be lower than that offered to horses with MFM and normal PAS staining for glycogen. Due to these diagnoses, nutritional recommendations for MFM are best made based on muscle biopsy results.

For horses diagnosed with MFM, dietary recommendations center around providing quality protein and specific amino acids to support rebuilding the affected contractile proteins in muscle fibers. Further, dietary antioxidants are recommended since oxidative stress is likely a cause of the degeneration in the muscle tissues. Since there is no evidence that diets low in nonstructural carbohydrates (NSC) and high in fat are helpful for horses diagnosed with MFM (contrary to those with PSSM), and added dietary fat is a potential source of oxidative stress, focus is typically placed on moderate NSC, moderate fat formulated concentrates with higher levels of quality protein. Recommendations for Warmbloods include balanced concentrates containing 12-14% crude protein, 20-30% NSC, and 4-8% fat (4-6% fat for Warmbloods; 6-8% fat for endurance Arabians). Forage recommendations for MFM horses include 1.5-2% body weight of good-quality grass or grass/legume mixed hays.

Because some Warmbloods exhibit both high glycogen staining and desmin aggregates, dietary recommendations for these specific horses are slightly altered. Instead of concentrates formulated with moderate NSC levels, concentrates containing lower NSC levels (<15% NSC) are recommended. Other nutrient level recommendations for MFM are not changed: 12-14% crude protein, 4-8% fat. The forage and supplement recommendations for these horses are also consistent with horses exhibiting typical biopsy results and symptoms of MFM.

In addition, supplemental amino acids are essential for horses diagnosed with MFM. Research conducted by Kentucky Equine Research in collaboration with Valberg indicated that supplementation containing a specific form of the amino acid cysteine, along with specific branched chain amino acids and high levels of bioavailable essential amino acids, supported improvement of MFM symptoms. The supplement used in the study was MFM Pellet. The form of cysteine provided is extremely important because many forms are not readily absorbed by the horse. Antioxidant supplementation is also helpful, and possibly essential for MFM horses, including highly bioavailable natural vitamin E (Nano-E), and coenzyme Q10 (Nano-Q10).

Management and exercise protocols recommended for MFM horses also play important roles in working with affected horses. Daily turnout for as long as possible with ample room for movement can be helpful. Grazing on moderate-quality, grazed-down pastures is often appropriate for MFM horses, but consultation with a veterinarian or equine nutritionist may be needed to determine whether an individual horse may be sensitive to NSC or caloric content of fresh pasture.

Exercise programs vary between Arabians and Warmbloods diagnosed with MFM. Arabian horses need consistent daily exercise to prevent episodes of tying-up and high serum CK. Warmbloods with MFM need a regular exercise schedule to increase structural protein turnover in muscles, but they also need days off to repair muscle as well.

According to Valberg, “A long, low warm-up is important for MFM horses. Each individual horse seems to have its own optimal exercise program in terms of days in work and days of rest, and that needs to be achieved through trial and error. Many owners of MFM horses have found that three days of work then two days off works best for MFM horses.” More specific exercise recommendations can be found on Valberg’s website.

Unfortunately, an exact cause for MFM is not known at this time. While it is likely that there is a genetic component, a specific genetic defect has not been confirmed. There are genetic tests available that claim to diagnose MFM in horses, but these tests have not been validated, and published research has shown that the incidence of genetic mutations identified in these tests are not statistically different between horses diagnosed with MFM through muscle biopsy and the general population of horses.

For more information, check out Nutritional Considerations for Horses with Myopathies.

^*Valberg, S. J., E.C. McKenzie, L.V. Eyrich, J. Shivers, N.E. Barnes, and C.J. Finno. 2016. Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis. Equine Veterinary Journal 48(5):548-556.

^**Valberg, S.J., A.M. Nicholason, S.S. Lewis, R.A. Reardon, and C.J. Finno. 2017. Clinical and histopathological features of myofibrillar myopathy in Warmblood horses. Equine Veterinary Journal 49(6):739-745.

Another article of interest authored by Valberg may be: Valberg, S.J. 2021. Diagnosis and management of myofibrillar myopathy in Warmblood performance horses. In: Proc. American Association of Equine Practitioners 67:214-218.