// Clinical Study Applications & Research
Myolex’s investigational product has been used in a variety of clinical studies (across dozens of medical centers in the United States and Europe) under institutional review board (IRB) approval as a nonsignificant risk device with the potential as a pharmacodynamic biomarker of drug efficacy.
Myolex provides tailored software for clinical trial use, including HIPAA-compliant data collection, storage, and retrieval, to streamline its application in any clinical trial. We also provide a team of clinical associates to assist with the technique’s implementation and data interpretation.
Multiple peer-reviewed scientific articles support the potential value of this technology as a useful biomarker, showing its sensitivity to disease progression, and drug effects, reliability, and ease of use.
Myolex Technology has already been used in drug development programs of a variety of neuromuscular conditions including:
/ Amyotrophic lateral sclerosis (ALS)
/ Muscular dystrophy and congenital myopathies
/ Acquired muscle disease
/ Spinal muscular atrophy
/ Sarcopenia/Cachexia and muscle atrophy
/ Preclinical/animal-based research needs
/ General health issues
In previous studies, EIM data have been used to help evaluate the efficacy of investigational muscular therapies. Results from these studies indicate that EIM biomarkers may be able to help researchers reach an objective, early, go/no-go decision on a potential therapy with fewer subjects than would otherwise be possible with standard clinical measures.
NUMBER OF PATIENTS NEEDED FOR ALS TRIAL
- EIM (95)
- Questionnaire (220)
- Strength Testing (266)
Amyotrophic lateral sclerosis (ALS)
Data from clinical studies in ALS have confirmed the sensitivity of EIM to disease progression. EIM has been used to assess a variety of individual muscles in the upper and lower extremities as well as the tongue and thoracic musculature, providing detailed data on many different body regions that are affected by disease. Studies in both human subjects and rodent models confirm that EIM has the potential to identify an effective intervention long before other metrics can identify a change. (see references below) It is currently being included in studies by Biogen, Inc.
- Rutkove SB, Caress JB, Cartwright MS, Burns T, Warder J, et al. Electrical impedance myography as a biomarker to assess ALS progression. Amyotroph Lateral Scler. 2012 Sep;13(5):439-45. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422377/
- Rutkove SB, Caress JB, Cartwright MS, Burns TM, Warder J, David WS, Goyal N, Maragakis NJ, Benatar M, Sharma KR, Narayanaswami P, Raynor EM, Watson ML, Shefner JM. Electrical impedance myography correlates with standard measures of ALS severity. Muscle Nerve. 2014 Mar;49(3):441-3. PubMed PMID: 24273034.
- Li J, Sung M, Rutkove SB. Electrophysiologic biomarkers for assessing disease progression and the effect of riluzole in SOD1 G93A ALS mice. PLoS One. 2013 Jun 6;8(6):e65976. doi: 10.1371/journal.pone.0065976. Print 2013. PubMed PMID: 23762454; PubMed Central PMCID: PMC3675066. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0065976
Muscular dystrophy and congenital myopathies
Muscular dystrophies and congenital myopathies produce considerable pathological change in muscle that EIM can potentially readily detect. Studies evaluating Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy and congenital muscular dystrophy are identifying major alterations in the impedance data that correlate to functional and radiological measures of muscle. Additional animal studies have shown analogous alterations. It is currently being included a clinical trial in Duchenne muscular dystrophy conducted by Akashi Therapeutics.
- Schwartz S, Geisbush TR, Mijailovic A, Pasternak A, Darras BT, Rutkove SB. Optimizing electrical impedance myography measurements by using a multifrequency ratio: a study in Duchenne muscular dystrophy. Clin Neurophysiol. 2015 Jan;126(1):202-8. PubMed PMID: 24929900; PubMed Central PMCID: PMC4234696. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234696/
- Zaidman CM, Wang LL, Connolly AM, Florence J, Wong BL, Parsons JA, Apkon S, Goyal N, Williams E, Escolar D; DART-EIM Clinical Evaluators Consortium, Rutkove SB, Bohorquez JL. Electrical impedance myography in Duchenne muscular dystrophy and healthy controls: A multi-center study of reliability and validity. Muscle Nerve. 2015 Feb 20. PubMed PMID: 25702806.
- Rutkove SB, Geisbush TR, Mijailovic A, Shklyar I, Pasternak A, Visyak N, Wu JS, Zaidman C, Darras BT. Cross-sectional evaluation of electrical impedance myography and quantitative ultrasound for the assessment of Duchenne muscular dystrophy in a clinical trial setting. Pediatr Neurol. 2014 Jul;51(1):88-92. PubMed PMID: 24814059; PubMed Central PMCID: PMC4063877.
- Statland JM, Heatwole C, Eichinger K, Dilek N, Martens WB, Tawil R. Electrical impedance myography in facioscapulohumeral muscular dystrophy. Muscle Nerve. 2016 Feb 3. doi: 10.1002/mus.25065. [Epub ahead of print] PubMed PMID: 26840230.
Acquired muscle disease
EIM may be useful in the study of other neuromuscular conditions such as acquired muscle diseases (including dermatomyositis, polymyositis, inclusion body myositis) with the potential for better confirmation and higher accuracy than manual muscle testing. Our data suggest that EIM may be sensitive to both the presence of edema/inflammation as well as to more chronic changes, including the deposition of fat and connective tissue within the muscle.
- Tarulli A, Esper GJ, Lee KS, Aaron R, Shiffman CA, Rutkove SB. Electrical impedance myography in the bedside assessment of inflammatory myopathy. Neurology 2005;65:451-452.
- Rutkove SB, Aaron R, Shiffman CA. Localized bioimpedance analysis in neuromuscular disease. Muscle Nerve 2002;25:390-397.
Spinal muscular atrophy (SMA)
The evaluation of SMA remains an important potential application of EIM, as evidenced in animal models. Ongoing studies (Avexis Pharma, Inc and Roche, Inc) are including the use of EIM in this disease. EIM was also included as a potential biomarker in the NIH-funded NeuroNEXT biomarker study. The results of these studies will be forthcoming shortly.
- Kolb SJ, Coffey CS, Yankey JW, et al. NeuroNEXT Clinical Trial Network and on behalf of the NN101 SMA Biomarker Investigators. Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study. Ann Clin Transl Neurol. 2016 Jan 21;3(2):132-45. doi: 10.1002/acn3.283. eCollection 2016 Feb. PubMed PMID: 26900585; PubMed Central PMCID: PMC4748311.
- Arnold W, McGovern VL, Sanchez B, Li J, Corlett KM, Kolb SJ, Rutkove SB, Burghes AH. The neuromuscular impact of symptomatic SMN restoration in a mouse model of spinal muscular atrophy. Neurobiol Dis. 2016 Mar;87:116-23. doi: 10.1016/j.nbd.2015.12.014. Epub 2015 Dec 28. PubMed PMID: 26733414; PubMed Central PMCID: PMC4724465.
- Rutkove SB, Gregas MC, Darras BT. Electrical impedance myography in spinal muscular atrophy: a longitudinal study. Muscle Nerve. 2012 May;45(5):642-7. doi: 10.1002/mus.23233. PubMed PMID: 22499089.
- Jafarpoor M, Spieker AJ, Li J, Sung M, Darras BT, Rutkove SB. Assessing electrical impedance alterations in spinal muscular atrophy via the finite element method. Conf Proc IEEE Eng Med Biol Soc. 2011;2011:1871-4. doi: 10.1109/IEMBS.2011.6090531. PubMed PMID: 22254695; PubMed Central PMCID: PMC3398735.
Sarcopenia/Cachexia and muscle atrophy
EIM is also likely to be sensitive to any condition that causes wasting and weakness of muscles. In both animal and human research, data supports EIM’s high sensitivity to disuse atrophy whether it is due to orthopedic injury or primary muscle injury. EIM has also identified subtle disuse associated with space flight in animals.
- Aaron R, Esper GJ, Shiffman CA, Bradonjic K, Lee KS, Rutkove SB. Effects of age on muscle as measured by electrical impedance myography. Physiol Meas. 2006;27:953-9.
- Kortman HG, Wilder SC, Geisbush TR, Narayanaswami P, Rutkove SB. Age- and gender-associated differences in electrical impedance values of skeletal muscle. Physiol Meas. 2013 Dec;34(12):1611-22. Epub 2013 Oct 28. PubMed PMID: 24165434; PubMed Central PMCID: PMC3895401. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895401/
- Tarulli AW, Duggal N, Esper GJ, Garmirian LP, Fogerson PM, Lin CH, Rutkove SB. Electrical impedance myography in the assessment of disuse atrophy. Arch Phys Med Rehabil. 2009 Oct;90(10):1806-10. PubMed PMID: 19801075.
- Sung M, Li J, Spieker AJ, Spatz J, Ellman R, Ferguson VL, Bateman TA, Rosen GD, Bouxsein M, Rutkove SB. Spaceflight and hind limb unloading induce similar changes in electrical impedance characteristics of mouse gastrocnemius muscle. J Musculoskelet Neuronal Interact. 2013 Dec;13(4):405-11. PubMed PMID: 24292610. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653813/
- Li J, Spieker AJ, Rosen GD, Rutkove SB. Electrical impedance alterations in the rat hind limb with unloading. J Musculoskelet Neuronal Interact. 2013 Mar;13(1):37-44. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984464/
Preclinical/animal-based research needs
EIM has been studied for years, providing data to support its utility for assessing muscle conditions in animal models of disease. Using specialized electrode arrays, EIM has been employed in a variety of species, including mouse, rat, dog, and pig and in a variety of disorders ranging from models of ALS, muscular dystrophy, and SMA, to sarcopenia, injury, and disuse. We are equipped to assist researchers with the application of this technique for their specific application.
- Li J, Staats WL, Spieker A, Sung M, Rutkove SB. A technique for performing electrical impedance myography in the mouse hind limb: data in normal and ALS SOD1 G93A animals. PLoS One. 2012;7(9):e45004. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0045004
- Nie R, Sunmonu A, Chin AB, Lee KS, Rutkove, SB. Electrical impedance myography: Transitioning from human to animal studies. Clin Neurophysiol 2006 Aug;117(8):1844-9. http://www2.kobe-u.ac.jp/~toyoda/beefproj2/BEEF/REf2/Transitioning%20from%20human%20to%20animal%20studies.pdf
- Ahad MA, Rutkove SB. Electrical impedance myography at 50kHz in the rat: technique, reproducibility, and the effects of sciatic injury and recovery. Clin Neurophysiol. 2009 Aug;120(8):1534-8. PubMed PMID: 19570710. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762741/
- Sanchez B, Li J, Bragos R, Rutkove SB. Differentiation of the intracellular structure of slow- versus fast-twitch muscle fibers through evaluation of the dielectric properties of tissue. Phys Med Biol. 2014 May 21;59(10):2369-80. PubMed PMID: 24743385; PubMed Central PMCID: PMC4039363. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039363/
General health issues
The technology of Myolex has applications outside of muscle disease per se. Internal studies have shown that our noninvasive EIM technology can assist in providing assessment of % body fat and lean muscle mass, with accuracy approaching that of dual x-ray absorptiometry. This means that EIM has potential in diet and exercise therapies for the treatment of diabetes, pre-diabetes/metabolic syndrome, simple deconditioning, and obesity.