The Most Promising Research for a Cure Last Updated: February 7, 2012
  1. Exon skipping using antisense oligonucleotides - Exon skipping employs synthetic DNA-like molecules called antisense as a "DNA band-aid" to skip over the parts of the gene (exons) that block the effective creation of dystrophin.
  2. Stop codon read through - Around 15% of DMD patients have stop codon mutations. Some experimental molecules can cause muscle cells to "read through" or “ignore” erroneous stop signals in the  gene.
  3. Exon skipping with gene transfer - Exon skipping can also be induced by recombinant virus vectors containing modified small nuclear [sn] RNA gene.
  4. Gene therapies -Gene therapies typically employ recombinant virus vectors and aim to correct or induce genes to rescue the pathology of DMD.
  5. Cell therapies - Various types of stem cells give rise to muscle progenitor cells and potentially rescue muscular dystrophies.
  6. Utrophin Upregulation/HDAC Inhibition - Utrophin is a protein similar to dystrophin and compensate for loss of strength and function due to defective dystrophin in muscles.
  7. Myostatin inhibition -Myostatin inhibition leads to muscle hypertrophy and potentially ameliorate the pathology of muscular dystrophies.
  8. TGFβ Inhibition/Anti-Fibrosis - Various experimental molecules can block TGFβ-mediated collagen synthesis.
  9. NF-kB inhibition/anti inflammatory - Several experimental molecules reduces the adverse effects of NF-κB signaling.
  10. TNF-alpha inhibition - TNF-alpha is pro-inflammatory, pro-fibrotic, and pro-NFKB. TNF-α is found to be elevated in DMD and in mdx muscles.
  11. Anti-Oxidants - Anti-oxidants decrease muscle necrosis in dystrophic mdx mice and protects against reactive oxygen species.
  12. IGF-1 - A growth factor IGF-1 is involved in muscle hypertrophy.
  13. α7-integrin upregulation - Increasing α7-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis.
  14. nNOS pathway enhancement - nNOS is a member of dystrophin complex and involved in vasodilatation.
  15. Angiotensin converting enzyme (ACE) inhibitor/ beta-blocker for cardiomyopathy management - Angiotensin-converting enzyme inhibitors are used in the management of cardiomyopathy.
  16. Corticosteroid - Corticosteroid is a useful palliative treatment.
  17. Other - Other miscellaneous strategies.
THERAPY RESEARCHER DESCRIPTION NAME (if any) PHASE REFERENCE CLINICAL TRIALS (if any)
1 EXON SKIPPING USINg ANTISENSE OLIGONUCLEOTIDES     (return to top)
A PMO, morpholino targeting exon 51, AVI Biopharma, Muntoni F. Phosphorodiamidate morpholino oligomer targeting exon 51, avi-4658,  is well tolerated and restores dystrophin expression in duchenne muscular dystrophy (dmd) boys in a dose dependent manner. AVI-4568 Phase ll AVI BioPharma - News Release ClinicalTrials.gov Link
B PMO, morpholino targeting exon 45, 50 AVI Biopharma Phosphorodiamidate morpholino oligomer targeting exon 45 and 50 Pre-clinical AVI BioPharma - News Release
C PPMO targeting exon 50 AVI Biopharma Peptide conjugated phosphorodiamidate morpholino oligomer targeting exon 50. AVI - 5038 Development AVI news release February 5, 2010
D 2-'O-methyl antisense oligos (PS) exon 44 Prosensa, Aartsma-Rus A. 2-'O-methyl antisense oligos (PS) targeting exon 44. PRO044 Phase ll J Gene Med. 2009 Mar;11(3):257-66. ClinicalTrials.gov Link
E 2-'O-methyl antisense oligos (PS) exon 51 Prosensa, van Deutekom J. 2-'O-methyl antisense oligos (PS) targeting exon 51. PRO051 Phase ll N Engl J Med. 2007 Dec 27;357(26):2677-86. ClinicalTrials.gov Link
ClinicalTrials.gov Link
F Guanine Enhanced Exon skipping (6-thioguanine) Lu QL. 6-thioguanine enhances morpholino-mediated exon skipping. Animal Mol Ther. 2010 Apr;18(4):812-8.
G Vivo-morpholinos (vPMOs) Gene-Tools, Lu QL. Octa-guanidine conjugated to morpholinos. Animal Mol Ther. 2009 May;17(5):864-71.
H Exon-skipping Across the Human Dystrophin Gene Transcript Wilton S., Aartsma-Rus A, Van Ommen G Skip various exons that aren't now being covered by current trials. Cell Mol Ther. 2007 Jul;15(7):1288-96.
I Cocktail morpholinos targeting exon 51 Takeda S. Cocktail morpholinos targeting exon 51 induced highly efficient dystrophin expression. Animal Mol Ther. 2010 Sep 7
J Multiple-skipping ex6/8 Takeda S., Hoffman E., Partridge TA. Systemic Exon 6/8 double skipping demosntrated in dystrophic dogs/human cells. Animal Ann Neurol. 2009 Jun;65(6):667-76.
K Multiple-skipping ex 52/53 Wilton S. By-passing the nonsense mutation in the 4 CV mouse model of muscular dystrophy by induced exon skipping. Animal J Gene Med. 2009 Jan;11(1):46-56.
L 2'-O-Me RNA/ENA chimera ex45/46 Matsuo M., Sankyo biotech Induced exon 45 and 46 skipping. Cell Nucleic Acids Symp Ser (Oxf). 2004;(48):297-8.
M 2'-O-Me RNA/ENA chimera ex 19 Matsuo M., Sankyo biotech The exon 19-skipping activity of the RNA/ENA chimera was more than 40 times stronger than that of the corresponding conventional phosphorothioate oligodeoxynucleotide. Cell Oligonucleotides. 2004 Spring;14(1):33-40.
N Multiple-skipping ex 43/44, 45/51,45-51 van Deutekom JC. Double skipping of exon 43 and 44, exon 45 and 51 was achieved. Cell Am J Hum Genet. 2004 Jan;74(1):83-92.
O Antisense-induced exon skipping for duplications van Deutekom JC. The correction of DMD duplications by exon skipping depends on the specific exons targeted. Cell BMC Med Genet. 2007 Jul 5;8:43.
P Antisense oligonucleotide sequences targeting exon 53 Dickson G. 24 AOs of the PMO chemistry designed to target exon 53 of the DMD gene. Cell Neuromuscul Disord. 2010 Feb;20(2):102-10.
Q Chimeraplast-mediated exon skipping Bertoni C. Multiple alternative transcripts were induced by RNA/DNA oligonucleotides (chimeraplasts). Animal Hum Mol Genet. 2003 May 15;12(10):1087-99.
R Peptide nucleic acid antisense oligonucleotides mediated exon skipping Wood MJ. PNA and all PNA-peptide conjugates resulted in significant numbers of dystrophin-positive fibers in the injected tibialis anterior (TA) muscles. Animal Mol Ther. 2008 Jan;16(1):38-45.
S Muscle targeting peptide Enhanced Exon skipping Wood MJ. Muscle-targeting heptapeptide (MSP) fused to an arginine-rich cell-penetrating peptide (B-peptide) and conjugated to a morpholinos MSP-PMOs Animal Hum Mol Genet. 2009 Nov 15;18(22):4405-14.
T PEG-PEI copolymers Lutz GJ. Antisense oligonucleotides complexed with PEG-PEI copolymers. Animal Mol Ther. 2006 Jul;14(1):88-96.
U Nanopolymers Lutz GJ. Improve delivery of exon skipping oligonucleotides and concomitant dystrophin expression in skeletal muscle of mdx mice. Animal BMC Biotechnol. 2008 Apr 2;8:35.
V Systemic Therapy With Morpholino Oligomers for exon 23 Dickson G., Partridge TA, Lu QL. Mdx mice treated for 50 weeks showed a substantial dose-related amelioration of the pathology, Animal Mol Ther. 2010 Nov 23
particularly in the diaphragm.
W Systemic Therapy With 2'OMePS for exon 23 Partridge TA, Lu QL, Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles. Animal Proc Natl Acad Sci U S A. 2005 Jan 4;102(1):198-203.
X Physiological Characterization of Muscle Strength With Variable Levels of Dystrophin Restoration in mdx Mice Following Local Antisense Therapy for ex23 Wells D. A highly significant correlation between the number of dystrophin-positive fibers and resistance to contraction-induced injury. Animal Mol Ther. 2010 Oct 5.
Y Chimeric Peptide-PMO Conjugate Wood MJ. 100% dystrophin-positive fibers and near complete correction of the dystrophin transcript defect in all peripheral muscle groups. Cumulative, enhanced molecular and phenotypic correction. Animal mdx mice Mol Ther. 2010 Oct;18(10):1822-9.
Z octaguanidine-morpholino oligo conjugate Widrick JJ octaguanidine delivery moiety-Morpholino conjugate that targets exon 23 (VMO23), restored function to muscles of mdx mice VMO 23 Animal mdx mice Muscle Nerve. 2011 Oct;44(4):563-70. doi: 10.1002/mus.22126
AA antisense oligonucleotide PRO051 Goemans NM PRO051 induced detectable, specific exon-51 skipping at doses of 2.0 mg or more per kilogram systemic PRO051 Human N Engl J Med. 2011 Apr 21;364(16):1513-22
AB antisense 2'O-methyl oligonucleotides (2'OMePS) and cocktail phosphorodiamidate morpholino oligomers (morpholinos, or PMOs)  Yokota T multiple exon skipping (double exon skipping) shown here provides the prospect of choosing deletions that optimize the functionality of the truncated dystrophin protein for DMD patients 2'OMePS,PMO Animal. Dystrophic phenotype dog Methods Mol Biol. 2011;709:299-312
2 STOP CODON READ THROUGH      (return to top)
A Ataluren PTC Therapeutics Positive trends in muscle function and strength were observed at Week 48 in patients treated with PTC124 Phase llb Nature. 2007 May 3;447(7140):87-91. ClinicalTrials.gov Link
low-dose ataluren ClinicalTrials.gov Link
B RTC 13 and RTC14 Bertoni C. Determine efficacy of stop codon read through compounds identified by HTS at UCLA Cell J Exp Med. 2009 Sep 28;206(10):2285-97.
C Gentamicin Sweeney HL. After 6 months of gentamicin, dystrophin levels significantly increased.The immunogenic epitope resulting from readthrough Phase I J Clin Invest. 1999 Aug;104(4):375-81. ClinicalTrials.gov Link
D Negamycin Matsuda R. A dipeptide antibiotic restores Dystrophin Expression in Skeletal and Cardiac Muscles of mdx Mice J Biochem. 2003 Nov;134(5):751-8.
3 Exon Skipping with Gene Transfer      (return to top)
A U7 snRNA Mediated Exon Skipping Garcia L., Davies KE. Use adeno-associated viral (AAV) vector containing a modified U7 small nuclear [sn] RNA gene Animal Mol Ther. 2009 Jul;17(7):1234-40.
B U1 snRNA mediated Exon Skipping Bozzoni I, Amsterdam Molecular Therapeutics The gene encoding for the U1 snRNA, a small nuclear RNA involved in the recognition of the 5’-splice site and required for the first step of the splicing reaction, inserted into rAAV. AMT-080 Pre-clinical Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3758-63
C microRNA--miR-31 Cacchiarelli D In human DMD myoblasts treated with exon skipping, we demonstrate that miR-31 inhibition increases dystrophin rescue Human DMD Myoblast EMBO Rep. 2011 Feb;12(2):136-41
4 GENE THERAPIES      (return to top)
A Deliver microdystrophin via lentiviral vectors Kimura E., Chamberlain JS. Transplantation of primary fibroblasts engineered to express a micro-dystrophin together with a tamoxifen-inducible form of the myogenic regulator MyoD. Animal Hum Mol Genet. 2008 Aug 15;17(16):2507-17.
B Deliver minidystrophin found in BMD patient or constructed microdystrophin via rAAV Asklepios Biopharmaceutica Use a mini dystrophin gene, or microdystrophin with recombinant AAVs. A first clinical trial where patients received local AAV-microdystrophin injections in the arm muscle. Phase l J Transl Med. 2007 Sep 24;5:45. ClinicalTrials.gov Link
C Delivery of mini-dystrophin in two constructs (Trans-splicing) Duan D. One rAAV vector provides the CMV promoter/enhancer region, the second provides the SV40 polyadenylation signal Animal Nat Biotechnol. 2005 Nov;23(11):1435-9.
D Re-engineered AAV Samulski/Asklepios Reengineering the receptor footprints, antigenic and reduced hepatic tropism Animal Nat Biotechnol. 2010 Jan;28(1):79-82.
E AAV-9 Xiao X. Successful transduction in neonatal dog, system wide with immunogenicity Animal Molecular Therapy. 2010. Jun;18(8):15011508.
F Microutrophin delivery Chamberlain JS. Microutrophin delivery through rAAV6 increases lifespan and improves muscle function in dystrophic dystrophin/utrophin-deficient mice Animal Mol Ther. 2008 Sep;16(9):1539-45.
G Deliver microdystrophin via rAAV Chamberlain JS., Takeda S., Xiao X., Duan D., Mendell JR. Restores dystrophin-glycoprotein complex and improves sarcolemma integrity in the mdx Animal Circulation. 2003 Sep 30;108(13):1626-32.
H Dual High-Capacity Hybrid Viral Vector De Vries AAF. Transfer of the Full-Length Dystrophin-Coding Sequence into Muscle Cells by a Dual High-Capacity Hybrid Viral Vector with Site-Specific Integration Ability Animal J Virol. 2005 Mar;79(5):3146-62.
I ultrasound and microbubble mediated in vivo gene transfer. Petrof BJ., Wells D., Partridge TA. antisense oligonucleotides or gene transfer using ultrasound and microbubble Animal Mol Ther. 2002 Nov;6(5):687-93.
J Hybrid vector system Duan D. A hybrid vector system expands adeno-associated viral vector packaging capacity in a transgene-independent manner. Animal Mol Ther. 2008 Jan;16(1):124-30.
K Chimeraplast-mediated gene correction Bertoni C. Mutation correction by RNA/DNA oligonucleotides (chimeraplasts) Animal Hum Mol Genet. 2003 May 15;12(10):1087-99.
L Dystrophin Immunity in Duchenne’s Mendell JR. Dystrophin-specific T cells were detected after treatment with rAAV. Human N Engl J Med. 2010 Oct 7;363(15):1429-37.
Muscular Dystrophy
M Exon Exchange Approach Garcia L. Minigene was cotransfected with a variety of exon exchange constructions, differing in their annealing domains. Animal MDX mice PLoS One 2010 5:e10894
N Human artificial chromosomes (HACs) Kazuki Y Succeeded in complete correction of a genetic deficiency in iPS cells derived from a human Duchenne muscular dystrophy patient using the HAC technology Cell. iPS cells derived from a human Duchenne muscular dystrophy Nihon Rinsho. 2011 Dec;69(12):2142-7
O  8K-NBD peptide treatment to AAV9 minidystrophin gene Reay DP Increased levels of recombinant dystrophin expression suggesting that 8K-NBD treatment promoted an environment in muscle tissue conducive to higher levels of expression 8K-NBD & AAV9 Animal mdx mice Mol Med. 2012 Jan 5. doi: 10.2119/molmed.2011.00404
P Translational Optimized AAV Vector Bowles DE AAV2.5 vector was safe and well tolerated, lays the foundation of customizing AAV vectors that best suit the clinical objective AAV2.5 Phase 1 Mol Ther. 2011 Nov 8. doi: 10.1038/mt.2011.237
5 CELL THERAPIES      (return to top)
A Myoblast Transplantation Tremblay JP. Transplant myogenic precursors from healthy donors. Phase IA Mol Ther. 2009 Jul;17(7):1122-4.
B Mesoangioblast transplantation Cossu G. Myogenic cells derived from bone marrow grafts delivered to produce widespread skeletal muscle via distribution through the vasculature. Phase I (3 patients) Nature. 2006 Nov 30;444(7119):574-9., Cure Duchenne Founders Blog
C Transplantation of exon-skipping-engineered patient stem cells Torrente Y and Garcia L. lentiviral vectors expressing antisense oligonucleotides in order to induce an efficient exon skipping of CD133+ stem cells. Animal Cell Stem Cell. 2007 Dec 13;1(6):646-57.
D Hematopoietic cell transplantation Storb R. Intramuscular injection of freshly isolated muscle-derived cells from the HCT donor into dog recipients. Animal Mol Ther. 2008 Jul;16(7):1340-6.
E Embryonic Stem Cells Perlingeiro RCR. Functional skeletal muscle regeneration from differentiating embryonic stem cells. Animal Nat Med. 2008 Feb;14(2):134-43.
F Cord Blood Cells Zatz M. Stem cells from umbilical cord blood differentiate into myotubes and express dystrophin in vitro Cell Biol Cell. 2007 Apr;99(4):185-96.
G Muscle-derived stem cells Huard J. Transplanted MDSCs generated Animal Gene Ther. 2005 Aug;12(16):1264-74.
large grafts consisting primarily of numerous dystrophin positive
myocytes in mdx heart.
H iPS cells Heike T., Oshimura M. iPS cells have the potential to be used in clinical treatment of muscular dystrophies. Animal Mol Ther. 2010 Feb;18(2):386-93.
I Bone marrow stromal cells Dezawa M. Inducing skeletal muscle lineage cells from human and rat general adherent MSCs with an efficiency of 89%. Animal Science. 2005 Jul 8;309(5732):314-7.
J MGMT (P140K)-mediated enrichment strategy Gunning PW, Hardeman EC. Adult stem cells are given a gene that makes them resistant to chemotherapy, which is used to clean out damaged cells and allow the new stem cells to take hold. Animal Stem Cells. 2009 May;27(5):1098-108.
K Placental artery-derived endothelial (hPAE) cells Umezawa A. hPAE cells conferred dystrophin to myocytes of the 'immunocompetent' mdx mice with extremely high efficiency. Animal Hum Mol Genet. 2010 Nov 8.
L Menstrual blood-derived cells Umezawa A. Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne muscular dystrophy. Animal Mol Biol Cell. 2007 May;18(5):1586-94.
M Placenta-derived cells Umezawa A. In vivo implantation of placenta-derived cells into dystrophic muscles of immunodeficient mdx mice restored sarcolemmal expression of human dystrophin. Animal J Cell Physiol. 2010 Jun;223(3):695-702.
N Blocking the Myostatin Signal With a Dominant Negative Receptor Improves the Success of Human Myoblast Transplantation Tremblay JP. Blocking the Myostatin Signal With a Dominant Negative Receptor Improves the Success of Human Myoblast Transplantation in Dystrophic Mice. lentivirus pCMV-dnActRIIB; folistatin Animal mdx mice Mol Ther. 2010 Aug 10.
O Hematopoietic prostaglandin d synthase inhibitors Kamauchi S Oral administration of HQL-79 markedly suppressed prostaglandin D production, reduced necrotic muscle volume, and improved muscle strength in mdx dystrophic mice HQL-79 Animal mdx mice Brain Nerve. 2011 Nov;63(11):1261-9
P Human Adipose-Derived Mesenchymal Stromal cells Vieira NM GRMD dogs without immunosuppression are able to reach the host muscle and express human dystrophin hASCs systemically Animal GRMD Dogs Cell Transplant. 2011 Oct 14
Q human artificial chromosomes (HACs) Tedesco FS Stem cell-mediated transfer of a human artificial chromosome ameliorates muscular dystrophy HAC Vector Genetically corrected mesoangioblast. Animal mdx mice Sci Transl Med. 2011 Aug 17;3(96):96ra78
6 UTROPHIN UPREGULATION/HDAC INHIBITION      (return to top)
A A small molecule utrophin up-regulator BMN 195 BioMarin BMN 195 Program Discontinued due to Pharmaceutical and Pharmacokinetic Challenges. Handed back to Summit. See Summit 1100. BMN 195 Phase I BioMarin News release August 2, 2010
B TAT Utrophin Ervasti J. Utrophin (Utr) or DeltaR4-21 "micro" utrophin (muUtr) protein modified with the cell-penetrating TAT protein transduction domain. Animal PLoS Med. 2009 May 26;6(5):e1000083.
C Heregulin Khurana TJ. Heregulin ameliorates the dystrophic phenotype in mdx mice with utrophin upregulation. Animal Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13856-60.
D Valproic acid Kaufman SJ. Activated PI3/AKT/mTOR pathway and Ameliorates Pathology in a Mouse Model. Animal Am J Pathol. 2009 Mar;174(3):999-1008.
E L-arginine de la Porte S. Utrophin upregulation via NO and HDAC pathways. Animal Neurobiol Dis. 2005 Oct;20(1):123-30.
F GW501516 Jasmin BJ. PPARbeta/delta agonist stimulates utrophin A expression in skeletal muscle fibers. Animal Hum Mol Genet. 2009 Dec 1;18(23):4640-9.
G IL6 Takeda S. Interleukin 6 induces overexpression of the sarcolemmal utrophin in neonatal mdx skeletal muscle. Animal Hum Gene Ther. 2002 Mar 1;13(4):509-18.
H A small molecule utrophin up-regulator SMT C1100 Summit plc, Davies KE. Summit plc and Davies are continuing with BM195 (now C1100) and working on reformulated follow up compounds C1100 Phase I -reformulated compound Summit News Release
7 MYOSTATIN INHIBITION      (return to top)
A Anti myostatin antibody Wyeth Pharmaceuticals, WagnerKR., Khurana TS. Announced it will not continue development of MYO-029 for muscular dystrophy. MYO-029 Stamulumab Phase I/ll Nature. 2002 Nov 28;420(6914):418-21.
B Myostatin inhibitor Acceleron Pharma Soluble activin receptor type IIB or ActRIIB ACE-031 Phase ll Acceleron Pharma News Release May 5, 2010 ClinicalTrials.gov Link
C rAAV to overexpress a secretable dominant negative myostatin Sweeney HL. Systemic myostatin inhibition via liver-targeted gene transfer in normal and dystrophic mice. Animal PLoS One. 2010 Feb 11;5(2):e9176.
D AAV delivery of follistatin Mendell JR. Alternatively spliced cDNA of follistatin (FS344) delivered by adeno-associated virus (AAV) to muscle. Animal Muscle Nerve. 2009 Mar;39(3):283-96.
E Myostatin propeptide gene delivery Xiao X. Myostatin propeptide gene delivery by adeno-associated virus serotype 8 vectors enhances muscle growth and ameliorates dystrophic phenotypes in mdx mice. Animal Muscle Nerve. 2009 Mar;39(3):283-96.
F Propeptide systemic delivery via RAAV8 vector Foster K. Intravenous Transfer of Myostatin Propeptide Leads to Systemic Functional Improvements of Slow but Not Fast Muscle. Animal Rejuvenation Res. 2009 Apr;12(2):85-94.
G Systemic follistatin via AAV type 1 vector Kaspar B. AAV1-FS344 injected into the quadriceps induced pronounced and durable increases in muscle size and strength in monkey. Animal Sci Transl Med. 2009 Nov 11;1(6):6ra15.
H Follistatin induction via Histone deacetlyase inhibitors Puri PL., Sartorelli V. Deacetylase Inhibitors Increase Muscle Cell Size by Promoting Myoblast Recruitment and Fusion through Induction of Follistatin. Animal Dev Cell. 2004 May;6(5):673-84.
I Follistatin induction via nitric oxide Clementi E., Cossu G. NO and cGMP induce expression of follistatin, and this secreted protein mediates their action in myogenesis. Animal J Cell Biol. 2006 Jan 16;172(2):233-44.
J Recombinant myostatin antagonist Salerno S. Short-term blockade of myostatin, through stage-specific administration of a myostatin antagonist, significantly enhanced muscle regeneration. Myst-Ant1,2,3 Animal Mol Ther. 2007 Aug;15(8):1463-70.
K FS I-I Tsuchida K. Myostatin inhibition by a follistatin-derived peptide ameliorates the pathophysiology of muscular dystrophy model mice. Animal Acta Myol. 2008 Jul;27:14-8.
L Myostatin Exon Skipping Dickson G. Antisense-induced Myostatin Exon Skipping Leads to Muscle Hypertrophy in Mice Following Octa guanidine Morpholino Oligomer Treatment. Animal Mol Ther. 2010 Oct 5.
8 TGFβ Inhibition/Anti-Fibrosis      (return to top)
A Losartan Dietz HC. Selective competitive angiotensin II receptor type 1 receptor antagonist, down regulates expression of TGF-beta. Cozaar Animal Nat Med. 2007 Feb;13(2):204-10.
B Imatinib mesilate Costa MC., Zhou L. TGF Blocker. Improves regeneration after injury. Gleevec, Imatinib Animal J Neuroimmunol. 2009 Jul 25;212(1-2):93-101.
C Suramin Huard J. TGF-β1 blocker. Antifibrotic effects in injured skeletal muscle after laceration. Germanin Animal J Appl Physiol. 2003 Aug;95(2):771-80.
D Halofuginone Anderson JE. Blocks TGFβ-mediated collagen synthesis. Pre-clinical Am J Physiol Heart Circ Physiol. 2008 Apr;294(4):H1550-61. Halotherapeutics News
E Pirfenidone Hoey AJ TGF-beta antagonist, pirfenidone, reduces cardiac fibrosis. Animal Muscle Nerve. 2006 Sep;34(3):327-34.
F Formoterol Lynch G. Beta(2)-adrenoceptor agonist (beta(2)-agonist) improves muscle function in dystrophic mdx mice. Animal Neuromuscul Disord. 2007 Jan;17(1):47-55.
G Osteopontin Miceli C., Spencer M., Hoffman E. Thought to promote fibrosis, elevated levels found in humans w/ DMD. continue to evaluate osteopontin as a therapeutic target for DMD. Animal J Clin Invest. 2009 Jun;119(6):1583-94.
H Tamoxifen Vainzof M. Estrogen receptor modulator. act on TGF-beta.Tamoxifen increases muscular strength of the mdx dystrophic mice. Animal Abstracts from 10th International Congress of World Muscle Society
I Bowman-Birk inhibitor concentrate (BBIC) Sweeney HL. BBIC treatment increases mass and strength, while decreasing fibrosis in skeletal muscles of the mdx mouse. Animal J Appl Physiol. 2010 Nov;109(5):1492-9.
J Activin IIB receptor blockade Sweeney HL. Systemic inhibition of activin IIB receptor signaling via adeno-associated virus (AAV)-mediated gene transfer Animal Muscle Nerve. 2010 Nov;42(5):722-30.
K BMP antagonists 't Hoen PA. BMP antagonists enhance myogenic differentiation and ameliorate the dystrophic phenotype in a DMD mouse model. Noggin, dorsomorphin and LDN-193189 Animal Neurobiol Dis. 2011 Feb;41(2):353-60.
9 NF-kB inhibition/anti inflammatory      (return to top)
A Flavocoxid Messina S., Vita G. Anti-inflammatory, anti-oxidant and NF-kB inhibition properties. Animal Exp Neurol. 2009 Dec;220(2):349-58.
B Curcumin Zhu MS NF-kB inhintor, it improved sarcolemmic integrity and enhanced muscle strength after intraperitoneal (i.p.) injection. Animal Mol Cells. 2008 Jun 30;25(4):531-7.
C UDCA Carlson CG. Treatment with inhibitors of the NF-κB pathway improves whole body tension development in the mdx mouse. Animal Neuromuscul Disord. 2009 Feb;19(2):131-9.
D NBD (Nuclear factor-kappa B inhibitory peptide) Kumar A Matrix metalloproteinase-9 inhibition ameliorates pathogenesis and improves skeletal muscle regeneration in muscular dystrophy. Animal Hum Mol Genet. 2009 Jul 15;18(14):2584-98.
E NFκB/NBD peptides , (pyrollidine dithiocarbamate, PDTC) Siegel A. Chronic treatment with agents that stabilize cytosolic IkappaB-alpha enhances survival and improves resting membrane potential in mdx. Animal Neurobiol Dis. 2005 Dec;20(3):719-30
F HQL-79 Urade Y Prostaglandin (D)2 synthase inhibitor suppresses Muscular Necrosis. Animal Am J Pathol. 2009 May;174(5):1735-44.
G Tβ4 RegeneRx, Spurney C., Nagaraju K. Naturally occurring peptide, downregulates inflam cytokines and NF-kB, upregulates AkT surival kinases, Regulates F and G actins. Thymosim Beta 4 Animal PLoS One. 2010 Jan 29;5(1):e8976.
H Cromolyn Neto HS, Pollina C., Grounds MD. Mast cell stabilizer, Disodium cromoglycate protects dystrophin-deficient muscle fibers from leakiness. Animal Muscle Nerve. 2008 Jan;37(1):61-7.
I L-Arginine Mornet D. L-Arginine Decreases Inflammation and Modulates the Nuclear Factor-{kappa}B/Matrix Metalloproteinase Cascade in Mdx Muscle Fibers. Animal Am J Pathol. 2008 Jun;172(6):1509-19.
J Arginine butyrate Nagaraju K., Faust Pharmaceuticals Arginine butyrate treatment improved grip strength and decreased fibrosis in the gastrocnemius muscle. FP0023 Animal PLoS One. 2010 Jun 21;5(6):e11220.
K Haelan 951/BBIC Tseng BS. Sweeney L., Walter G., Vandenbourne K. Protease inihibitor, Anti-inflammatory, neuroprotection? Cell FASEB J. 2009 Oct;23(10):3325-34.
L Inhibition of the IKK/NF-kappaB pathway by AAV gene transfer Wang B. Inhibition of IKKα or IKKβ in dystrophic muscle reduces the adverse effects of NF-κB signaling. Animal Gene Ther. 2010 Dec;17(12):1476-83.
10 TNF-alpha inhibition      (return to top)
A BKT-104 (oral TNF alpha inhibitor) Carvalho AAS, Feder D. A small molecule which has potent anti-inflammatory properties. Animal Annual Meeting of American Academy of Neurology, 2009
B cV1q Grounds MD. Anti TNF-alpha monoclonal (Centocor) Reduced muscle necrosis and long-term benefits in dystrophic mdx mice. Animal Neuromuscul Disord. 2008 Mar;18(3):227-38.
C LMP-420 Bizario J. LMP-420 treated mice showed significantly-decreased CK levels and amelioration of muscular degeneration. Animal Presentation at NIDB 2008 (PDF)
D Etanercept De Luca A. Pharmacological approaches to oxidative stress and altered calcium homeostasis in fxl impairment and degenreation. Animal Neuropathol Appl Neurobiol. 2007 Jun;33(3):344-59.
11 Anti-Oxidants      (return to top)
A Green Tea Extract Ruegg U, Stoward PJ. Antioxidant Green tea extract decreases muscle necrosis in mdx mice and protects against reactive oxygen species. Phase ll Am J Clin Nutr. 2002 Apr;75(4):749-53.
B Coenzyme Q10 Simonsen R. Restore cellular creatinine stores (regulate cellular energy and protein turnover). Phase ll Biochim Biophys Acta. 1995 May 24;1271(1):281-6. ClinicalTrials.gov Link
C Melatonin Ruegg T., Acuña-Castroviejo D. Anti-oxidant Melatonin prevents oxidative stress-mediated mitochondrial permeability transition and death in skeletal muscle cells. Clinical J Pineal Res. 2010 Apr;48(3):282-9.
D N-Acetylcysteine Allen DG. N-acetylcysteine (NAC) provided protection against dystrophic muscle damage in the mdx mouse. Animal J Physiol. 2008 Apr 1;586(7):2003-14
E Catena/Idebenone/Sovrima® Santhera Pharmaceuticals Small molecule optimized to facilitate the transport of electrons within mitochondria, which is necessary for the production of cellular energy. It is a synthetic analogue of ubiquinone and is a potent antioxidant. Phase lll Santhera Pharmaceuticals presentation ClinicalTrials.gov Link
ClinicalTrials.gov Link
F (Epigallocatechin-3-Gallate (EGCG) Ruegg UT. Green tea extract and its major polyphenol ()-epigallocatechin gallate improve muscle function in a mouse model for Duchenne muscular dystrophy. Animal Am J Physiol Cell Physiol. 2006 Feb;290(2):C616-25. ClinicalTrials.gov Link
G Alpha-lipoic acid/l-carnitine Mornet D. Treatment decreased the plasmatic creatine kinase level, the antioxidant enzyme activity, and lipid peroxidation products in mdx diaphragm. Animal Am J Pathol. 2007 Feb;170(2):633-43.
H BN 82270 De Luca A. A novel chimeric compound dually acting as calpain inhibitor and anti-oxidant. Animal Neuromuscul Disord. 2006 Apr;16(4):237-48.
I Glutamine Mok E., Hankard R. Delay protein breakdown. l-Glutamine administration reduces oxidized glutathione and MAP kinase signaling in dystrophic muscle of mdx mice. Phase III Pediatr Res. 2008 Mar;63(3):268-73.
J Pargyline, an MAO inhibitor Canton M. Pargyline, an MAO inhibitor, reduced ROS accumulation along with a beneficial effect on the dystrophic phenotype. Animal Hum Mol Genet. 2010 Nov 1;19(21):4207-15.
12 IGF-1      (return to top)
A IGF-1 analogue (LR-IGF-1) Lynch GS., Rutter M. Insulin-like growth factor-I analogue protects muscles of dystrophic mdx mice from contraction-mediated damage. Animal Exp Physiol. 2008 Nov;93(11):1190-8.
B Glucose regulated protein 94 Barton ER, Argon Y. GRP94 may be a new therapeutic target to boost IGF-1. Animal Biochim Biophys Acta. 2010 Feb;1803(2):333-41.
C Igf1 codelivery with rAAV/microdystrophin Chamberlain JS. Phenotypic improvement of dystrophic muscles by rAAV/microdystrophin vectors is augmented by Igf1 codelivery. Animal Mol Ther. 2005 Sep;12(3):441-50.
D Increlex - (mecasermin (rDNA origin) injection) Ipsen Inc. replacement for IGF-1 Increlex Ph 1 Pilot Study Safety and Efficacy Study of IGF-1 in Duchenne Muscular Dystrophy - Full Text View - ClinicalTrials.gov
13 α7-integrin upregulation      (return to top)
A Laminin 111 Burkin DJ., Prothelia, Inc. Increases α7-integrin expression. Laminin-111 protein therapy prevents muscle disease in the mdx mouse model for Duchenne muscular dystrophy. Animal mdx mice Proc Natl Acad Sci U S A. 2009 May 12;106(19):7991-6. Prothelia - Pipeline
B α7-integrin regulation Kaufman SJ. Increasing {alpha}7β1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression. Animal Am J Physiol Cell Physiol. 2008 Feb;294(2):C627-40.
C  Laminin-111 Gawlik KI Transgenic expression of Laminin α1 chain does not prevent muscle disease in the mdx mouse model for Duchenne muscular dystrophy. laminin 111 Animal mdx, mdxLM alpha 1 mice Am J Pathol. 2011 Apr;178(4):1728-37
14 nNOS pathway enhancement      (return to top)
A PDE5 inhibition Des Rosiers C., Wagner KR., Campbell KP., Beavo JA., Asakura A. Regulate excitation-contraction coupling and vasodilatation and glucose uptake during exercise. Role in muscle repair and regeneration.Sildenafil has been shown to delay and even prevent heart failure in the DMD animal model. Revatio, sildenafil citrate (Viagra) Phase ll Proc Natl Acad Sci U S A. 2008 May 13;105(19):7028-33. ClinicalTrials.gov Link
B PDE5 inhibition Yasuhara SE. The vasoactive drug tadalafil, a phosphodiesterase 5 inhibitor, administered to mdx mice ameliorated muscle damage. Tadalafil (Cialis) Animal PLoS One. 2007 Aug 29;2(8):e806. ClinicalTrials.gov Link
C nNOS upregulator Clementi E. a nitric oxide-releasing derivative of flurbiprofen. HCT 1026 Animal Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):264-9.
15 Angiotensin-converting enzyme (ACE) inhibitor/ beta-blocker for cardiomyopathy management      (return to top)
A Angiotensin-converting enzyme (ACE) inhibitor Scott WA. Angiotensin-converting enzyme inhibitors in the management of cardiomyopathy. 10 of 26 patients (43%) with Duchenne muscular dystrophy responded to the use of enalapril. Enalapril Clinical Am J Cardiol. 2006 Sep 15;98(6):825-7 ClinicalTrials.gov Link
B Beta-blocker Nakanishi T. Beta-blocker medication is known to improve the prognosis of chronic heart failure of adults. Carvedilol Phase lV Circ J. 2006 Aug;70(8):991-4. ClinicalTrials.gov Link
C A study to combat heart disease in muscular dystrophy Mendell JR. Improve cardiac care by establishing the best medication regimen and to look at the best time to start treatment to protect the patient from heart failure. Clinical News release from Nationwide Hospital 7/14/2009
D ACE receptor blocker Fakhfakh R Losartan enhances the success of myoblast transplantation losartan Dystrophic mice Cell Transplant. 2011 Apr 29
16 Corticosteroid      (return to top)
A Prednisone Myer E. A useful palliative treatment. Clinical Lancet. 1974 Dec 14;2(7894):1409-12.
B Deflazacort Flores D. DF appears as an alternative to prednisone preserving its benefits but with fewer side-effects. Calcort in UK Clinical Neuromuscul Disord. 1991;1(4):261-6.
C Long-circulating prednisolone liposomes. Weller C Liposomal encapsulation is not superior in treatment efficacy compared with conventional prednisolone In improving Motor performance of young dystrophic mdx mice polyethylene-glycol-coated liposomes encapsulating prednisolone was compared with free prednisolone Animal mdx mice J Neurosci Res. 2012 Jan 18. doi: 10.1002/jnr.22825
17 Other      (return to top)
A IL-15 Lynch GS. Anabolic cytokine Interleukin-15 administration improves diaphragm muscle pathology and function in dystrophic mdx mice. Animal Am J Pathol. 2005 Apr;166(4):1131-41.
B Albuterol Lynch GS. Low dose beta(2)-adrenoceptor agonist administration improves muscle function in dystrophic mdx mice without increasing fatigue. Salbutamol Animal Neuromuscul Disord. 2007 Jan;17(1):47-55.
C Velcade and MLN273 Lisanti MP. Blocking proteosome. blocks the degradation of dystrophin and dystrophin-associated proteins in mdx mice. Animal Cell Cycle. 2007 May 15;6(10):1242-8.
D Human Growth Hormone (HGH) Politano L.. Induces a hypertrophic response associated with a significant reduction of brain natriuretic peptide plasma levels and a slight improvement of systolic function. Clinical Eur Heart J. 2003 Apr;24(7):664-72.
E Methazolamide or dichlorphenamide Segalat L. Carbonic anhydrase inhibitors. C. elegans-based screen coupled with a mouse model validation strategy. Animal Hum Mol Genet. 2009 Nov 1;18(21):4089-101.
F MG-132 Lisanti MP. Proteasome Inhibitor (MG-132) Treatment of mdx Mice Rescues the Expression and Membrane Localization of Dystrophin and Dystrophin-Associated Proteins. Animal Cell Cycle. 2007 May 15;6(10):1242-8.
G PG-873637 Isfort RJ. Corticortopin releasing factor 2 receptor agonist treatment significantly slows disease progression in mdx mice. Animal BMC Med. 2007 Jul 12;5:18.
H GsMTx4 Sachs F., Allen DG. Streptomycin and the spider venom toxin GsMTx4, prevented the rise of resting [Ca2+]i and partially prevented the decline of tetanic [Ca2+]i and force. Cell J Physiol. 2005 Jan 15;562(Pt 2):367-80.
I Debio 025/ CypD/ CsA Molkentin JD., Ruegg UT., Bernardi P. Cyclophilin D Inhibitor; anti-apoptotic properties. as, effective as or slightly better than, prednisone in mitigating muscular dystrophy in the mdx mouse. Animal Neuromuscul Disord. 2010 Jul 14.
J Creatine Monohydrate Tarnopolsky MA. Nutritional therapy improves function and complements corticosteroid intervention in mdx mice. Phase III Muscle Nerve. 2006 Jan;33(1):66-77.
K PAMH (Pyridine Activator of muscle cell hypertrophy) Olson EN. Potential target for muscle growth. Animal Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2870-5.
L Membrane sealant poloxamer 188 Metzger JM., Phrixus Pharmaceuticals In vivo administration of poloxamer 188 to dystrophic mice instantly improved ventricular geometry and blocked the development of acute cardiac failure. P-188 Pre-Clinical J Clin Invest. 2010 Apr 1;120(4):1140-50. Phrixus News
M TRPV2 Iwata Y. Dominant-negative inhibition of Ca2+ influx via TRPV2 ameliorates muscular dystrophy in animal models. Animal Hum Mol Genet. 2009 Mar 1;18(5):824-34.
N Far Infrared Radiation Nedd K. Far Infrared radiation for 30 to 40 minutes per treatment session. Phase I Clinical Trial database ClinicalTrials.gov Link
O GLPG0492 Galapagos NV. Orally available small molecule that Galapagos has developed in its Selective Androgen Receptor Modulator (SARM) program. pre-clinical Galapagos News Release, May 20, 2010
P Biglycan Fallon JR. Biglycan regulates the expression and sarcolemmal localization of dystrobrevin, syntrophin, and nNOS. Pre-Clinical FASEB J. 2006 Aug;20(10):1724-6. Tivorsan.com Link
Q Flt-1 gene knockout Asakura A. Increasing the vasculature in DMD may ameliorate the histological and functional phenotypes associated with this disease. Mdx mice Crossed with Flt-1 gene knockout mice Animal. Mdx mice & Flt-1 gene knockout mice Hum Mol Genet. 2010 Nov 1;19(21):4145-59.
R transduction of full-length dystrophin Ishizaki M Rescue from respiratory dysfunction by transduction of full-length dystrophin to diaphragm via the peritoneal cavity in utrophin/dystrophin double knockout mice intraperitoneal injection of a helper-dependent adenovirus vector (HDAdv) containing the full-length dystrophin expression cassett Animal dko mice Mol Ther. 2011 Jul;19(7):1230-5. doi: 10.1038/mt.2011.58
S Histone deacetylase inhibitors Consalvi S The ability of HDACi to counter the progression of muscular dystrophies points to HDACs as a crucial link between specific genetic mutations and downstream determinants of disease progression suberoylanilide hydroxamic acid (SAHA) and ITF2357 (givinostat) Animal mdx mice Mol Med. 2011 May-Jun;17(5-6):457-65. doi: 10.2119/molmed.2011.00049
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