Table 4 Summary table of conditions discussed and related treatments
From: The evolving therapeutic landscape of genetic skeletal disorders
| Â | Disease | Treatments (stage if still in trials) | Additional Notes |
|---|---|---|---|
FGFR3 spectrum disorders | Achondroplasia | Statins (in mouse models) GH Vosoritide (CNP analogue, phase 3) TransCon CNP (phase 2 (Q3 2019)) TA-46 (soluble FGFR3 ligand trap, Therachon AG, phase 1) Infagratinib (preclinical studies complete) Meclozine (drug repurposing, phase 1) | -Studies of Statin related therapy show conflicting results. |
Hypochondroplasia | Somatropin (human growth hormone) | Â | |
High Bone Mass | Osteopetrosis | Interferon gamma 1b Human stem cell transplantation siRNA therapy (in vitro cell lines) RANKL replacement (mouse models) | siRNA therapy: For AD Osteopetrosis RNAKL replacement: For RANKL AR Osteopetrosis |
Low Bone Mass | Osteoporosis Pseudoglioma syndrome | Lithium carbonate (mice studies promising) Anti-sclerostin therapy (mouse model) | Lithium carbonate: -limited data from pilot human studies |
Osteogenesis Imperfecta | Bisphosphonates, GH Teriparitide RANKL inhibitors (Denosumab, clinical trials) Anti-sclerostin therapy (Setrusumab, BPS804) TGF-β inhibitors (Fresolimumab, phase 1) Stem cell (mesenchymal, inutero transplant) Raloxifene Gene silencing –siRNA, shRNA, ODNs Vibraflex device (BCH), Physical rehab training | GH: -GH in OI in type IV Teriparitide: -TOPAZ trial (Teriparitide and Zolendronate, recruiting) Setrusumab: -phase 2B trial (ASTEROID study) Fresolimumab: -phase 1 trial in US (recruitment) Stem cell: -BOOSTB4 trial (gaining trial approval) Gene silencing: -At invitro and ex vivo stage. Vibraflex: -conflicting evidence for benefit | |
Low Bone Mineral Density | Hypophosphatasia | Asfotase Alfa (approved) Gene therapies (animal studies) Anti-sclerostin therapy (BPS804, human proof of concept trials) Bone marrow transplant, Teriparatide | Asfotase Alfa: For perinatal, infantile, juvenile HPP |
-X-Linked Hypophosphataemia | Anti FGFR23 mab; Burosumab (Crysvita) | Approved by NICE Sept 2018 | |
Metaphyseal Dysplasia | -Metaphyseal Chondrodysplasia Schmid type | Carbamazepine (phase 1–2, Newcastle led) | Recruiting 2019. |
-Schwartz Jampel Synd. | Carbamazepine (case reports) | Â | |
FOP | Fibrodysplasia Ossificans Progressiva | REGN 2477 (Anti Activin A, phase 2) Palovarotene (selective retinoid agonist, phase 3) Rapamycin Other small molecule therapies in development. | Â |
Genetic Bone Tumours | Hereditary Multiple Exostoses | Palovarotene (phase 2) | Â |