Drug discovery
16
drugs
With orphan designations
Overview
Limb-girdle muscular dystrophy (LGMD) encompasses over 30 inherited neuromuscular disorders characterized by progressive proximal muscle weakness affecting hip and shoulder girdles. Caused by autosomal dominant or recessive mutations, it presents with variable onset (childhood to adulthood) and progression [1][7][16]. Cardiac/respiratory involvement occurs in specific subtypes, requiring multidisciplinary care [1][12]. No disease-modifying therapies exist, though emerging molecular treatments are under investigation [3][13][17].
Population
Affects both sexes equally, with combined prevalence estimates ranging from 1:14,500 to 1:123,000 [1][5][12]
LGMD2A (calpainopathy) accounts for 30% of cases, while sarcoglycanopathies and dysferlinopathies comprise 15-20% each [2][7]
Founder mutations increase subtype prevalence regionally (e.g., CAPN3 variants in Spain/Brazil, FKRP in Northern Europe) [2][5]
Therapies
Supportive care: Physical/occupational therapy, orthotics, and respiratory/cardiac monitoring [1][14][19]
Pharmacologic: Corticosteroids show limited efficacy in LGMD2C-F subtypes [1][17]
Experimental: Gene therapy (AAV-mediated hASM for LGMD2B), exon skipping, and CRISPR-Cas9 editing in preclinical stages [3][13][15]
Categories: rare genetic diseases, rare neurological diseases
Drug Discovery Landscape
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
primary human satellite cell-derived muscle stem cells derived from patients with genetic muscular dystrophy (CAPN3 c.550delA mutation) and engineered with CRISPR-Cas technology to express wild type CAPN3 protein | gene editing enzymes | FDA | 2025-11-06 | — | MyoPax GmbH |
Adeno-associated virus sector serotype rh74 containing the human SGCG gene | gene therapies | EMA | 2025-02-26 | — | Sarepta Therapeutics Ireland Limited |
Prednisone | small molecules | FDA | 2024-03-05 | — | Sarcomed AB |
Adeno-associated virus vector serotype 9/rh74 containing the human CAPN3 gene and a target sequence of cardiac-specific microRNA | gene therapies | EMA | 2023-10-13 | — | Atamyo Therapeutics |
Adeno-associated viral vector serotype 9 expressing fukutin-related protein | gene therapies | EMA | 2023-02-15 | — | AskBio France |
Patidistrogene bexoparvovec | gene therapies | EMA | 2023-02-15 | — | Sarepta Therapeutics Ireland Limited |
Adeno-associated virus serotype 8 expressing the human gamma-sarcoglycan gene | gene therapies | EMA | 2022-05-16 | — | Atamyo Therapeutics |
Adeno-associated virus serotype 9 expressing the human fukutin related protein and target sequence of the miR-208a | gene therapies | EMA | 2022-01-14 | — | Atamyo Therapeutics |
Adeno-associated virus serotype rh74 containing the human sarcoglycan beta gene | gene therapies | EMA | 2020-12-09 | — | Sarepta Therapeutics Ireland Limited |
Ribitol | small molecules | EMA | 2020-10-19 | — | Bridge Bio Europe B.V. |
nandrolone | small molecules | FDA | 2019-12-04 | — | Sarcomed AB |
ribitol | small molecules | FDA | 2019-01-16 | — | ML Bio Solutions, Inc. |
One, two, three, or four antisense oligonucleotides of Phosphorodiamidate morpholino oligomer combination that skips exons 4, 5, 6, and 7 of the gamma sarcoglycan (SGCG) gene | oligonucleotides | FDA | 2017-07-18 | — | Kurt+Peter Foundation |
Amino acids 2-506 of the wild-type human histidyl-tRNA synthetase [ATYR1940] | proteins | EMA | 2017-02-27 | — | Voisin Consulting Life Sciences |
Recombinant human histidyl-tRNA synthetase | proteins | FDA | 2017-02-23 | — | aTyr Pharma |
Angiotensin (1-7) | peptides | FDA | 2013-11-26 | — | Constant Therapeutics LLC |