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The H2 blocker famotidine suppresses progression of ossification of the posterior longitudinal ligament in a mouse model.

Maeda Y, Yamamoto K, Yamakawa A, Aini H, Takato T, Chung UI, Ohba S - RMD Open (2015)

Bottom Line: Ossification of the posterior longitudinal ligament (OPLL) of the spine is a common human myelopathy that leads to spinal cord compression.Oral administration of famotidine suppressed the progression of OPLL-like ectopic ossification and reduced mortality in Enpp1 (ttw/ttw) mice when administration began at 4 weeks of age, early in the development of ossification.This study points to the use of famotidine as a disease-modifying drug for ectopic ossification of spinal soft tissue, including OPLL.

View Article: PubMed Central - PubMed

Affiliation: Department of Sensory and Motor System Medicine, The University of Tokyo Graduate School of Medicine, Tokyo , Japan ; Division of Clinical Biotechnology , The University of Tokyo Graduate School of Medicine , Tokyo , Japan.

ABSTRACT

Background: Ossification of the posterior longitudinal ligament (OPLL) of the spine is a common human myelopathy that leads to spinal cord compression. No disease-modifying drug for OPLL has been identified, whereas surgery and conservative management have been established.

Objectives: To evaluate the therapeutic potential of the H2 blocker famotidine for ectopic ossification in the cervical spine in an OPLL mouse model.

Methods: The H2 blocker famotidine was orally administered to Enpp1 (ttw/ttw) mice, a model of OPLL, at either 4 or 15 weeks of age. Radiological and survival rate analyses were performed to assess the effects of famotidine on OPLL-like lesions and mortality in Enpp1 (ttw/ttw) mice.

Results: Oral administration of famotidine suppressed the progression of OPLL-like ectopic ossification and reduced mortality in Enpp1 (ttw/ttw) mice when administration began at 4 weeks of age, early in the development of ossification.

Conclusions: This study points to the use of famotidine as a disease-modifying drug for ectopic ossification of spinal soft tissue, including OPLL.

No MeSH data available.


Related in: MedlinePlus

Survival rates of famotidine-treated Enpp1ttw/ttw mice. Survival rates were analysed in Enpp1ttw/ttw mice treated with famotidine from 4 weeks of age (▪: 5 male and 8 female mice at the outset) and 15 weeks of age (▴: 5 male and 7 female mice at the outset) as well as controls (♦: 3 male and 8 female mice at the outset). X-axes indicate ages of mice.
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RMDOPEN2015000068F3: Survival rates of famotidine-treated Enpp1ttw/ttw mice. Survival rates were analysed in Enpp1ttw/ttw mice treated with famotidine from 4 weeks of age (▪: 5 male and 8 female mice at the outset) and 15 weeks of age (▴: 5 male and 7 female mice at the outset) as well as controls (♦: 3 male and 8 female mice at the outset). X-axes indicate ages of mice.

Mentions: We assessed survival rates in Enpp1ttw/ttw mice with or without famotidine. To examine the effect of famotidine on more advanced ectopic ossification in cervical spines, we created another treatment group, with famotidine administered from 15 weeks of age. Thus, we analysed Enpp1ttw/ttw mice treated with famotidine from 4 weeks of age (5 males and 8 females), those treated from 15 weeks of age (5 males and 7 females), and controls that received no famotidine (3 males and 8 females). Figure 3 shows that mice exposed to famotidine from 4 weeks of age lived longer than those exposed to famotidine from 15 weeks of age or controls. There was no marked difference in survival rates between the latter two groups. Female mice died earlier than male mice. These data suggest that famotidine administration from an early phase of the disease progression can reduce mortality caused by ectopic ossification in the cervical spine, but exhibits little effect on more advanced disease.


The H2 blocker famotidine suppresses progression of ossification of the posterior longitudinal ligament in a mouse model.

Maeda Y, Yamamoto K, Yamakawa A, Aini H, Takato T, Chung UI, Ohba S - RMD Open (2015)

Survival rates of famotidine-treated Enpp1ttw/ttw mice. Survival rates were analysed in Enpp1ttw/ttw mice treated with famotidine from 4 weeks of age (▪: 5 male and 8 female mice at the outset) and 15 weeks of age (▴: 5 male and 7 female mice at the outset) as well as controls (♦: 3 male and 8 female mice at the outset). X-axes indicate ages of mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612692&req=5

RMDOPEN2015000068F3: Survival rates of famotidine-treated Enpp1ttw/ttw mice. Survival rates were analysed in Enpp1ttw/ttw mice treated with famotidine from 4 weeks of age (▪: 5 male and 8 female mice at the outset) and 15 weeks of age (▴: 5 male and 7 female mice at the outset) as well as controls (♦: 3 male and 8 female mice at the outset). X-axes indicate ages of mice.
Mentions: We assessed survival rates in Enpp1ttw/ttw mice with or without famotidine. To examine the effect of famotidine on more advanced ectopic ossification in cervical spines, we created another treatment group, with famotidine administered from 15 weeks of age. Thus, we analysed Enpp1ttw/ttw mice treated with famotidine from 4 weeks of age (5 males and 8 females), those treated from 15 weeks of age (5 males and 7 females), and controls that received no famotidine (3 males and 8 females). Figure 3 shows that mice exposed to famotidine from 4 weeks of age lived longer than those exposed to famotidine from 15 weeks of age or controls. There was no marked difference in survival rates between the latter two groups. Female mice died earlier than male mice. These data suggest that famotidine administration from an early phase of the disease progression can reduce mortality caused by ectopic ossification in the cervical spine, but exhibits little effect on more advanced disease.

Bottom Line: Ossification of the posterior longitudinal ligament (OPLL) of the spine is a common human myelopathy that leads to spinal cord compression.Oral administration of famotidine suppressed the progression of OPLL-like ectopic ossification and reduced mortality in Enpp1 (ttw/ttw) mice when administration began at 4 weeks of age, early in the development of ossification.This study points to the use of famotidine as a disease-modifying drug for ectopic ossification of spinal soft tissue, including OPLL.

View Article: PubMed Central - PubMed

Affiliation: Department of Sensory and Motor System Medicine, The University of Tokyo Graduate School of Medicine, Tokyo , Japan ; Division of Clinical Biotechnology , The University of Tokyo Graduate School of Medicine , Tokyo , Japan.

ABSTRACT

Background: Ossification of the posterior longitudinal ligament (OPLL) of the spine is a common human myelopathy that leads to spinal cord compression. No disease-modifying drug for OPLL has been identified, whereas surgery and conservative management have been established.

Objectives: To evaluate the therapeutic potential of the H2 blocker famotidine for ectopic ossification in the cervical spine in an OPLL mouse model.

Methods: The H2 blocker famotidine was orally administered to Enpp1 (ttw/ttw) mice, a model of OPLL, at either 4 or 15 weeks of age. Radiological and survival rate analyses were performed to assess the effects of famotidine on OPLL-like lesions and mortality in Enpp1 (ttw/ttw) mice.

Results: Oral administration of famotidine suppressed the progression of OPLL-like ectopic ossification and reduced mortality in Enpp1 (ttw/ttw) mice when administration began at 4 weeks of age, early in the development of ossification.

Conclusions: This study points to the use of famotidine as a disease-modifying drug for ectopic ossification of spinal soft tissue, including OPLL.

No MeSH data available.


Related in: MedlinePlus