CureDuchenne: Research Index

Research Index

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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.More info

	therapy	researcher	description	name	phase	reference
1	Exon skipping using antisense oligonucleotides						Close
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

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.More info

Exon skipping with gene transfer

Exon skipping can also be induced by recombinant virus vectors containing modified small nuclear [sn] RNA gene.More info

Gene therapies

Gene therapies typically employ recombinant virus vectors and aim to correct or induce genes to rescue the pathology of DMD.More info

	therapy	researcher	description	name	phase	reference
1	GENE THERAPIES						Close
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

Cell therapies

Various types of stem cells give rise to muscle progenitor cells and potentially rescue muscular dystrophies.More info

	therapy	researcher	description	name	phase	reference
1	CELL THERAPIES						Close
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

Utrophin Upregulation

Utrophin is a protein similar to dystrophin and compensate for loss of strength and function due to defective dystrophin in muscles.More info

	therapy	researcher	description	name	phase	reference
1	UTROPHIN UPREGULATION/HDAC INHIBITION						Close
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

Myostatin inhibition

Myostatin inhibition leads to muscle hypertrophy and potentially ameliorate the pathology of muscular dystrophies.More info

	therapy	researcher	description	name	phase	reference
1	MYOSTATIN INHIBITION						Close
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.

TGFβ Inhibition/Anti-Fibrosis

Various experimental molecules can block TGFβ-mediated collagen synthesis. More info

	therapy	researcher	description	name	phase	reference
1	TGFβ Inhibition/Anti-Fibrosis						Close
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.

NF-kB inhibition/anti inflammatory

Several experimental molecules reduces the adverse effects of NF-κB signaling.More info

	therapy	researcher	description	name	phase	reference
1	NF-kB inhibition/anti inflammatory						Close
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

TNF-alpha is pro-inflammatory, pro-fibrotic, and pro-NFKB. TNF-α is found to be elevated in DMD and in mdx muscles. More info

11.

Anti-Oxidants

Anti-oxidants decrease muscle necrosis in dystrophic mdx mice and protects against reactive oxygen species. More info

	therapy	researcher	description	name	phase	reference
1	Anti-Oxidants						Close
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

A growth factor IGF-1 is involved in muscle hypertrophy.More info

13.

α7-integrin upregulation

Increasing α7-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis.More info

14.

nNOS pathway enhancement

nNOS is a member of dystrophin complex and involved in vasodilatation.More info

15.

Angiotensin converting enzyme (ACE) inhibitor/ beta-blocker for cardiomyopathy management

Angiotensin-converting enzyme inhibitors are used in the management of cardiomyopathy. More info

16.

Corticosteroid

Corticosteroid is a useful palliative treatment.More info

17.

Other

Other miscellaneous strategies.More info

	therapy	researcher	description	name	phase	reference
1	Other						Close
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