Gene Therapy for Fibrodysplasia Ossificans Progressiva: Feasibility and Obstacles

Elisabeth M.W. Eekhoff; Ruben D. de Ruiter; Bernard J. Smilde; Ton Schoenmaker; Teun J. de Vries; Coen Netelenbos; Edward C. Hsiao; Christiaan Scott; Nobuhiko Haga; Zvi Grunwald; Carmen L. De Cunto; Maja di Rocco; Patricia L.R. Delai; Robert J. Diecidue; Vrisha Madhuri; Tae Joon Cho; Rolf Morhart; Clive S. Friedman; Michael Zasloff; Gerard Pals; Jae Hyuck Shim; Guangping Gao; Frederick Kaplan; Robert J. Pignolo; Dimitra Micha

doi:10.1089/hum.2022.023

Gene Therapy for Fibrodysplasia Ossificans Progressiva: Feasibility and Obstacles

Elisabeth M.W. Eekhoff, Ruben D. de Ruiter, Bernard J. Smilde, Ton Schoenmaker, Teun J. de Vries, Coen Netelenbos, Edward C. Hsiao, Christiaan Scott, Nobuhiko Haga, Zvi Grunwald, Carmen L. De Cunto, Maja di Rocco, Patricia L.R. Delai, Robert J. Diecidue, Vrisha Madhuri, Tae Joon Cho, Rolf Morhart, Clive S. Friedman, Michael Zasloff, Gerard PalsJae Hyuck Shim, Guangping Gao, Frederick Kaplan, Robert J. Pignolo, Dimitra Micha

Periodontology

Research output: Contribution to Journal › Review article › Academic › peer-review

Abstract

Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease, in which soft connective tissue is converted into heterotopic bone through an endochondral ossification process. Patients succumb early as they gradually become trapped in a second skeleton of heterotopic bone. Although the underlying genetic defect is long known, the inherent complexity of the disease has hindered the discovery of effective preventions and treatments. New developments in the gene therapy field have motivated its consideration as an attractive therapeutic option for FOP. However, the immune system's role in FOP activation and the as-yet unknown primary causative cell, are crucial issues which must be taken into account in the therapy design. While gene therapy offers a potential therapeutic solution, more knowledge about FOP is needed to enable its optimal and safe application.

Original language	English
Pages (from-to)	782-788
Number of pages	7
Journal	Human gene therapy
Volume	33
Issue number	15-16
Early online date	16 Aug 2022
DOIs	https://doi.org/10.1089/hum.2022.023
Publication status	Published - Aug 2022

Funding

E.M.W.E.: PI clinical trials of Regeneron Pharmaceuticals, indirect EU-IMI by Astra Zeneca; Clementia Pharmaceuticals (an Ipsen Company). G.G. and J.-H.S.: funding sources are NIAMS of the NIH under R21AR077557, the AAVAA Therapeutics, IFOPA. F.S.K.: research investigator: Clementia/Ipsen, Regeneron. R.J.P.: R.J.P. is an investigator on FOP clinical trials sponsored by Clementia Pharmaceuticals (an Ipsen Company) and Regeneron Pharmaceuticals. R.J.P is a consultant for Ipsen, Regeneron, Incyte, Biocryst, and Keros, but receives no personal compensation for these activities. N.H.: Past Research Investigator: Clementia/Ipsen. Z.G. consultant and speaker for Ipsen BiopharmaceuticalsInc. Regeneron. C.L.D.C.: Clementia/Ipsen PI, Novartis: speaker, Biogen: speaker, Novo Nordisk: speaker. M.D.R. Disclosures last 2 years: Maja Di Rocco received fees for lectures or participation on advisory board by Sanofi, Takeda, Ultragenix, Orchard. Participating in FOP trials. P.D.: PI for Ipsen Move trial. T.-J.C. Funding source: research grant of the Genome Technology to Business Translation Program from the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning of the Republic of Korea Government. E.H.: ECH is an investigator on FOP clinical trials sponsored by Clementia Pharmaceuticals (an Ipsen Company). No other conflict of interest related to this article.

Funders	Funder number
Ministry of Science, ICT & Future Planning of the Republic of Korea Government
National Institute of Arthritis and Musculoskeletal and Skin Diseases	R01AR078230
National Research Foundation

Keywords

ALK2 mutation
fibrodysplasia ossificans progressiva
gene therapy
heterotopic ossification
RNA

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1089/hum.2022.023

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Eekhoff, E. M. W., de Ruiter, R. D., Smilde, B. J., Schoenmaker, T., de Vries, T. J., Netelenbos, C., Hsiao, E. C., Scott, C., Haga, N., Grunwald, Z., De Cunto, C. L., di Rocco, M., Delai, P. L. R., Diecidue, R. J., Madhuri, V., Cho, T. J., Morhart, R., Friedman, C. S., Zasloff, M., ... Micha, D. (2022). Gene Therapy for Fibrodysplasia Ossificans Progressiva: Feasibility and Obstacles. Human gene therapy, 33(15-16), 782-788. https://doi.org/10.1089/hum.2022.023

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abstract = "Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease, in which soft connective tissue is converted into heterotopic bone through an endochondral ossification process. Patients succumb early as they gradually become trapped in a second skeleton of heterotopic bone. Although the underlying genetic defect is long known, the inherent complexity of the disease has hindered the discovery of effective preventions and treatments. New developments in the gene therapy field have motivated its consideration as an attractive therapeutic option for FOP. However, the immune system's role in FOP activation and the as-yet unknown primary causative cell, are crucial issues which must be taken into account in the therapy design. While gene therapy offers a potential therapeutic solution, more knowledge about FOP is needed to enable its optimal and safe application.",

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Eekhoff, EMW, de Ruiter, RD, Smilde, BJ, Schoenmaker, T , de Vries, TJ, Netelenbos, C, Hsiao, EC, Scott, C, Haga, N, Grunwald, Z, De Cunto, CL, di Rocco, M, Delai, PLR, Diecidue, RJ, Madhuri, V, Cho, TJ, Morhart, R, Friedman, CS, Zasloff, M, Pals, G, Shim, JH, Gao, G, Kaplan, F, Pignolo, RJ & Micha, D 2022, 'Gene Therapy for Fibrodysplasia Ossificans Progressiva: Feasibility and Obstacles', Human gene therapy, vol. 33, no. 15-16, pp. 782-788. https://doi.org/10.1089/hum.2022.023

TY - JOUR

T1 - Gene Therapy for Fibrodysplasia Ossificans Progressiva

T2 - Feasibility and Obstacles

AU - Eekhoff, Elisabeth M.W.

AU - de Ruiter, Ruben D.

AU - Smilde, Bernard J.

AU - Schoenmaker, Ton

AU - de Vries, Teun J.

AU - Netelenbos, Coen

AU - Hsiao, Edward C.

AU - Scott, Christiaan

AU - Haga, Nobuhiko

AU - Grunwald, Zvi

AU - De Cunto, Carmen L.

AU - di Rocco, Maja

AU - Delai, Patricia L.R.

AU - Diecidue, Robert J.

AU - Madhuri, Vrisha

AU - Cho, Tae Joon

AU - Morhart, Rolf

AU - Friedman, Clive S.

AU - Zasloff, Michael

AU - Pals, Gerard

AU - Shim, Jae Hyuck

AU - Gao, Guangping

AU - Kaplan, Frederick

AU - Pignolo, Robert J.

AU - Micha, Dimitra

PY - 2022/8

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N2 - Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease, in which soft connective tissue is converted into heterotopic bone through an endochondral ossification process. Patients succumb early as they gradually become trapped in a second skeleton of heterotopic bone. Although the underlying genetic defect is long known, the inherent complexity of the disease has hindered the discovery of effective preventions and treatments. New developments in the gene therapy field have motivated its consideration as an attractive therapeutic option for FOP. However, the immune system's role in FOP activation and the as-yet unknown primary causative cell, are crucial issues which must be taken into account in the therapy design. While gene therapy offers a potential therapeutic solution, more knowledge about FOP is needed to enable its optimal and safe application.

AB - Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease, in which soft connective tissue is converted into heterotopic bone through an endochondral ossification process. Patients succumb early as they gradually become trapped in a second skeleton of heterotopic bone. Although the underlying genetic defect is long known, the inherent complexity of the disease has hindered the discovery of effective preventions and treatments. New developments in the gene therapy field have motivated its consideration as an attractive therapeutic option for FOP. However, the immune system's role in FOP activation and the as-yet unknown primary causative cell, are crucial issues which must be taken into account in the therapy design. While gene therapy offers a potential therapeutic solution, more knowledge about FOP is needed to enable its optimal and safe application.

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KW - fibrodysplasia ossificans progressiva

KW - gene therapy

KW - heterotopic ossification

KW - RNA

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U2 - 10.1089/hum.2022.023

DO - 10.1089/hum.2022.023

M3 - Review article

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SN - 1557-7422

VL - 33

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JO - Human gene therapy

JF - Human gene therapy

IS - 15-16

ER -

Gene Therapy for Fibrodysplasia Ossificans Progressiva: Feasibility and Obstacles

Abstract

Funding

Keywords

UN SDGs

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