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Effects of Altered Immunity in XLH on Dental and Periodontal Infection

Award Number: K99DE034722
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/15/2026
PERIOD OF PERFORMANCE END DATE: 05/14/2028

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Effects of Altered Immunity in XLH on Dental and Periodontal Infection - PROJECT SUMMARY/ABSTRACT X-linked hypophosphatemia (XLH) is caused by inactivating mutations in the PHEX (phosphate-regulating gene with homology to endopeptidases on the X chromosome) gene, resulting in di sturbances in systemic and local mineral metabolism, increased levels of circulating fibroblast growth factor 23 (FGF23), and hypophosphatemic rickets. In XLH, pulp necrosis and dental abscesses are prevalent at all ages and risk of periodontitis increases with age. These contribute to decreased oral and systemic health. While mechanisms underlying dental disorders in XLH have been assumed to result from mineralization defects, no studies have directly investigated or demonstrated this connection. Conventional therapy for XLH includes daily oral phosphorus and vitamin D or the use of inactivating FGF23 antibody (FGF23Ab; burosumab) reduces excess FGF23. Dental health outcomes have been unclear, with both preclinical studies and human case studies reporting conflicting results of worse outcomes, no improvement, or some improvement, compared to conventional therapy. Burosumab only addresses heightened FGF23 levels and does not correct local mineral metabolism changes or other primary or secondary effects from PHEX loss-of-function. PHEX is expressed by a wide range of cells and mutations alter other signaling pathways that contribute to non-skeletal defects observed in XLH; no current XLH treatment options address these alterations. Recently, it was discovered that pediatric and adult patients with XLH were reported to have a persistent state of inflammation, but it remains unknown how this is associated with dental and periodontal manifestations of XLH. There is a lack of information on effects of XLH on immune cells (monocytes, neutrophils, T-cells, and B-cells) and cytokine profiling. Treatment effects on immune cells and cytokines were never evaluated to understand how these interventions modulate immunological status associated with PHEX mutations. XLH patients experience very high rates of pulp infection, necrosis, abscess, and tooth loss, and current treatments do not fully prevent this. Similarly, these patients experience high rates of periodontal disease later in life that is only partially reduced by conventional therapy. Local changes in immune response and microbiome have never been investigated. Based on the preliminary data summarized above, we hypothesize that dental and periodontal infections in XLH result, in part, from altered immune response. This hypothesis will be tested by 3 Specific Aims: (1) Define altered immune and inflammatory profile in the Hyp mouse model of XLH; (2) Identify immune mechanisms contributing to increased dental pulp infections in XLH and (3) Investigate immune mechanisms associated with periodontal disease in XLH. Successful completion of this proposal will provide critical new insights into how XLH affects immune function and the associated dental and periodontal manifestations. This can make a difference in therapeutic approaches for XLH that could improve oral health and quality of life.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $116,937 )
2026	2026	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Oral Diseases and Disorders Research	000	1	5/13/2026	NEW	$116,937
														Subtotal = $116,937

Grand Total All Awards = $116,937

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Effects of Altered Immunity in XLH on Dental and Periodontal Infection

Award Number: K99DE034722

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/15/2026

PERIOD OF PERFORMANCE END DATE: 05/14/2028

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