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. Author manuscript; available in PMC: 2022 Mar 1.
Published in final edited form as: Trends Cell Biol. 2020 Dec 1;31(3):197–210. doi: 10.1016/j.tcb.2020.11.003

Table 1.

Reported therapeutic strategies for FKRP-associated dystroglycanopathies.

Treatment Model Results Refs
Small molecules and metabolites Prednisolone + Alendronate FKRPP448L mouse

  • Decreased CK levels, infiltration (TA), degeneration and CNF (TA)

  • Increased functionally glycosylated α-DG (TA)

 [61]
Tamoxifen and Raloxifen FKRPP448L mouse

  • Decreased infiltration (TA), CNF (TA), CK levels and collagen accumulation (HA-QUA-TA-DIA)

  • Improved skeletal muscle and respiratory function

 [62]
Pantetic Acid Zebrafish Tg [hsp70l-hFKRP(L276I)-IRES-eGFP]

  • Decreased pericardiac edema

  • Increased life span and muscle birefringence

 [39]
Ribitol FKRPP448L mouse

  • Decreased fibrosis (HA-TA-DIA)

  • Increased functionally glycosylated α-DG (HA-TA-DIA)

  • Improved skeletal muscle and respiratory function

 [66]
iPSC-derived human embryoid bodies

  • Increased functionally glycosylated α-DG

 [60]
NAD+ Zebrafish FKRP morphants

  • Decreased muscle degeneration

  • Increased concentration of laminin at the myotendinous junction

  • Improved muscle fiber organization, skeletal muscle function and myotendinous junction

 [36]
4BPPNit iPSC-derived cortical neurons

  • Increased functionally glycosylated α-DG

 [59]
Gene Therapy AAV9-CAG-FKRP FKRPP448L mouse IP and IV injection:

  • Decreased CNF, CK, fibrosis (HA-DIA)

  • Increased functionally glycosylated α-DG and LOA (HA-TA-DIA-GAS)

  • Improved skeletal muscle and respiratory function

  • Partial recovery of metabolic alterations

 [69, 72, 73]
FKRP L276IKI mouse IV injection:

  • Decreased CK, CNF

  • Increased in functionally glycosylated α-DG and cardiac function (EF and FS)

  • Improved skeletal muscle function

 [45]
rAAV2/9-Des-mFkrp FKRPL276Imouse IM and IV injection:

  • Decreased CNF (PSO)

  • Increased functionally glycosylated α-DG and laminin binding (GAS-GLU-pSo)

 [47]
AAV9-CAG-LARGE1 FKRPP448L mouse IP injection:

  • Decreased CNF

  • Increased functionally glycosylated α-DG and laminin binding (HA-TA-DIA)

 [70]
AAVrh74-MCK-GALGT2 FKRPP448L mouse IM injection:

  • Decreased CNF (QUA-TA-GAS), membrane instability (TA) and muscle loss (QUA-TA-GAS)

  • Increased regenerating fibers

 [71]
Cell therapy pLenti-CAG (hFKRP)-Rsv satellite cells FKRP L276IKI mouse TA IM injection of cells:

  • Increased functionally glycosylated α-DG (TA-HA)

  • Improved skeletal muscle function

 [81]
Pax3/7 iPSC-derived myogenic progenitors FKRPP448L-NSG mouse TA IM injection of cells:

  • Decreased CNF

  • Increased functionally glycosylated α-DG

  • Improved skeletal muscle function

 [49]

Abbreviations: CNF, centrally nucleated fibers; DIA, diaphragm; EF, ejection fraction; FS, fractional shortening; GAS, gastrocnemius; GLU, gluteus; IP, intraperitoneal; IV, intravenous; TA, tibialis anterior; HA, heart; QUA, quadriceps; PSO, psoas.