Research

HPP Research

Soft Bones funds research to better understand HPP with the goal of finding a cure.

We believe a cure is possible

With modern-day science of gene editing and gene therapy, we work closely with researchers and clinicians to champion collaboration, reduce duplication of effort, share findings and unite the global HPP community. We also work to position HPP as a favorable subject of research through a global HPP registry. Areas we support include:

Gene therapy and gene editing
CoRDS International HPP Contact Registry – Researcher access
Research of new therapies or improvement to existing therapy
New HPP investigators through annual $25,000 seed grant
HPP scientific exchange through other grants
HPP TeleECHO series. For information email ECHO@SoftBones.org

HPP Patient Registry

Soft Bones has partnered with Coordination of Rare Diseases at Sanford (CoRDS) to create an International HPP Contact Registry. The registry provides patients and caregivers with a secure means of making their basic disease information available to researchers without sacrificing privacy. By joining the registry, you can help researchers see the whole picture and gain valuable information for a disease that they know too little about. Information learned through the registry plays a vital role in improving treatments and finding a potential cure.

For more information, contact CoRDS at cords@sanfordhealth.org or (877) 658-9192.

You can also access the
CoRDS Participant Brochure,
CoRDS Registration Tip Sheet
CoRDS Podcast Info Card.
Once ready, you may register using the link below, or call the CoRDs office directly.

Soft Bones Grant Winners

Nan Hatch, DMD, PhD
2022

Fatma F.Mohamed, PhD
2021

Flavia Amadeu de Oliveira, PhD
2020

Dana Gaddy, PhD
2019

Dobrawa Napierala, PhD
2019

Kathryn Dahir, MD
2017

Brian Foster, PhD
2016, 2018

Luke Mortensen, PhD
2015

Steven Mumm, PhD
2014

Flavia Amadeu de Oliveira, PhD
Sanford Burnham Prebys Medical Discovery Institute- 2020

2020 Recipient – Flávia Amadeu de Oliveira, PhD, Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California The study objectives look to determine the efficacy of viral vector delivery of mineral-targeted tissue non-specific alkaline phosphatase (TNAP) to treat late onset or adult HPP.”I have a long-standing interest in bone biology, especially in the molecular mechanisms that regulate bone homeostasis,” said Dr.Amadeu de Oliveira.
“Overall, my goal through this research proposal is to test if chronic administration of mineral-targeted TNAP in HPP mice with superimposed chronic kidney disease, which manifests vascular calcification, may have adverse consequences. In doing so, I will also attempt to validate viral vector delivery of mineral-targeted TNAP to correct the soft bones disease in late-onset HPP mice. Overall, this study will contribute to devising safe and improved therapies for HPP,” she continued.”Overall, my goal through this research proposal is to test if chronic administration of mineral-targeted TNAP in HPP mice with superimposed chronic kidney disease, which manifests vascular calcification, may have adverse consequences. In doing so, I will also attempt to validate viral vector delivery of mineral-targeted TNAP to correct the soft bones disease in late-onset HPP miceOverall, this study will contribute to devising safe and improved therapies for HPP,” she continued.The Scientific Advisory Board for Soft Bones carefully considers grant applications and this year solicited submissions that would help advance gene therapy in HPP.
“The implications of this work may extend to all forms of HPP, not just adult,” says Dr.Jose Luis Millan, Soft Bones Scientific Advisory Board member and Professor of Human Genetics at Sanford Burnham Prebys Medical Discovery Institute. “The findings could be relevant to the entire HPP spectrum.”
Press Release: https://www.prnewswire.com/news-releases/soft-bones-inc-awards-its-2020-grant-to-sanford-burnham-prebys-researcher-to-promote-gene-therapy-advancements-in-hypophosphatasia-301176710.html

Brian Foster, PhD
The Ohio State University- 2016,2018

2016 and 2018 Recipient – Brian Foster, Ph.D., The Ohio State University 2016 – I study the biology of tooth development, focusing on factors that are important for proper tooth formation and function. My emphasis is on the mineralized (hard) tissues of the tooth that give it mechanical strength- the enamel, dentin, cementum, as well as the bone that forms the socket around the tooth. By better understanding how teeth develop, I hope to gain new insights that may one day improve approaches for repair and regeneration of dental tissues. Many people with HPP experience dental problems associated with the disease. A greater understanding of the effects of HPP on the bones and teeth has been gained from studies using a mouse model of HPP. This mouse model is a good representation of severe infantile HPP, however the severity of the disease prevents long-term studies, including those on therapies that may treat HPP-associated dental disease. As part of the Soft Bones research grant proposal, we aim to create new mouse models of HPP that vary in the severity of disease and location of tissues affected. These will include models that affect the bones and teeth, as well as those that primarily target the dental tissues. The novel HPP mouse models will then allow better controlled studies of how different therapies can prevent and repair HPP-associated skeletal and dental problems. These models will allow expansion of HPP research by additional researchers in the future, thus providing new resources to widen HPP-related research. With the support of the Soft Bones 2016 Research Grant, we have been able to analyze two new mouse models for dental disorders associated with HPP. The original mouse model of HPP that has been used for two decades has provided a wealth of information about all aspects of the disease, however, was limited by its severity that shortened its lifespan and restricted the types of studies that could be performed. These new HPP mouse models, developed in part with the grant, replicate the effects of HPP on bone and tooth development, but the later disease onset and targeted effects on hard tissues has translated into longer-lived HPP models that can be studied over a longer period to more advanced ages. One insight already provided by these novel models relates to the development of periodontal disease around teeth that have been affected by HPP. This work was recently published in the January 2017 issue of the Journal of Dental Research, one of the top ranking scientific journals in the field of Dentistry, Oral Surgery & Medicine. 2018 – As the recipient of a 2018 research grant from Soft Bones, Dr. Foster, in collaboration with Dr. Michael White, an Endocrinologist at Shriners Hospital for Children and Washington University in St. Louis, proposes to analyze primary teeth (deciduous or baby teeth) from individuals with hypophosphatasia (HPP). This study is the first of its kind to quantitatively analyze teeth from a large group of HPP subjects. Dr. Foster hopes to gain a better understanding of how dental problems correlate to skeletal, biochemical and genetic changes in individuals with HPP. In the future, this may help medical professionals predict the severity of HPP-associated dental disease, better treat dental disorders arising from HPP, or even estimate the overall course of disease.With this project, Dr. Foster and his team will continue building upon years of achievement in the field of HPP research, with a specific focus on the relationship between HPP and dental disorders. For several years, Dr. Foster has been studying mouse models of HPP to understand how the disorder affects the different hard tissues of teeth and supporting jaws, including enamel, dentin, cementum and bone. Dr. Foster won the 2016 Soft Bones research grant for his mouse model research, and the 2016 grant supported development of a new mouse model of HPP that was featured in the Journal of Dental Research.
2018 Press Release: https://softbones.org/wp-content/uploads/2022/12/Dr.-Brian-Foster-Grant-Announcement-2018-1.docx
2016 Press Release: https://www.globenewswire.com/fr/news-release/2016/03/28/951895/0/en/Soft-Bones-Inc-Awards-Its-Third-Grant-to-the-Ohio-State-University-Researcher-to-Promote-Work-in-Hypophosphatasia.html?culture=en-us

Steven Mum, PhD
Washington University School of Medicine- 2014

2014 Recipient – Steven Mumm, Ph.D., Washington University School of MedicineThe Soft Bones Foundation research grant helped us complete DNA sequencing of the tissue non-specific alkaline phosphatase gene (TNSALP or ALPL) for our pediatric hypophosphatasia (HPP) patients at The St. Louis Shriners Hospital for Children. In 2015, we published our findings in a paper entitled “Hypophosphatasia: Validation and expansion of the clinical nosology for children from 25 years of experience with 173 pediatric patients.” Here, we reported our TNSALP mutation findings along with clinical details from our pediatric patients diagnosed with Odonto, Childhood, or Infantile HPP. This detailed analysis allowed us to refine the nosology for HPP and separate the Childhood form into “Mild Childhood” and “Severe Childhood” forms. Our findings should improve understanding of HPP presentation, natural history, complications and prognosis.

We continue to evaluate the role that TNSALP mutations play in women who are diagnosed with osteoporosis and treated with bisphosphonates, and subsequently exhibit an unusual fracture called “atypical subtrochanteric femoral fracture. These unusual fractures resemble those seen in Adult HPP. We proposed that some of these women may, in fact, have HPP instead of osteoporosis, and published the first case in 2012. We received a two-year grant from the National Institutes of Health to study this and reported initial findings at the 2013 American Society for Bone and Mineral Research meeting. We presented a second case of a woman diagnosed with “osteoporosis” showing a documented HPP mutation who suffered one of these unusual fractures. Our findings suggest that while TNSALP mutations may not have a major role in causing these unusual fractures, that it is important to distinguish the rare Adult HPP patients from the more common osteoporosis patient population. In 2016, I co-authored a paper entitled “Adult hypophosphatasia treated with teriparatide: Report of 2 patients and review of the literature.” Here we reported mixed results for teriparatide therapy for HPP but concluded that teriparatide shows some benefit for Adult HPP, which may be dependent on the number of TNSALP mutations (1 or 2) and the specific mutation(s) carried by the HPP patient.