出生前の幹細胞治療は、希少な遺伝性疾患を胎児期に標的とする(Prenatal stem cell treatment targets rare genetic disease before birth)

2026-03-11  スタンフォード大学

＜関連情報＞

• https://news.stanford.edu/stories/2026/03/stem-cell-trial-fanconi-anemia-genetic-disease-research
• https://obgyn.onlinelibrary.wiley.com/doi/10.1002/pd.70077
• https://ashpublications.org/bloodadvances/article/8/17/4554/516943/In-utero-hematopoietic-stem-cell-transplantation

ファンコニ貧血患者コミュニティにおける出生前介入に対する意識 Attitudes Toward Prenatal Interventions in the Fanconi Anemia Community

Tony Lum, Catherine Lee, Tippi MacKenzie, Billie Lianoglou, Agnieszka Czechowicz
Prenatal Diagnosis  Published: 19 February 2026
DOI:https://doi.org/10.1002/pd.70077

ABSTRACT

Objective

In-utero cell and gene therapies may offer prenatal treatment options for inherited diseases. Preclinical data suggests in-utero (IU) hematopoietic stem cell transplantation (HSCT) could prevent Fanconi anemia (FA) related bone marrow failure without genotoxic conditioning or immune suppression. This study surveyed patient and caregiver attitudes within the FA community toward prenatal diagnosis, interventions, and clinical trials.

Methods

A multidisciplinary team created and distributed an online survey through the leading FA patient advocacy group. Respondents’ demographic, history, and treatment data were collected, and their attitudes toward prenatal diagnosis, IU therapies, and pregnancy termination were analyzed using univariable ordinal logistic regression.

Results

72 members from 18 countries completed the survey. Among the respondents, 76% were willing to undergo IU-HSCT if it was FDA approved, whereas 68% would consider enrolling in a clinical trial to assess the safety and efficacy of IU-HSCT or IU-gene therapy. 71% would undergo invasive prenatal testing in any at risk pregnancy to confirm FA and 56% were unlikely to terminate an affected pregnancy.

Conclusion

In-utero therapy is a developing alternate treatment strategy for rare, inherited diseases. Although electronic surveys have inherent limitations, this tool enabled efficient assessment of FA community attitudes with a favorable response to prenatal diagnosis and therapies. These insights encourage efforts to advance IU-cell and gene therapy clinical trials and to continue to evaluate community attitudes as these therapies develop. This work may also provide insights into the attitudes of other rare inherited disease communities.

Summary

• What is already known about this topic?
  • Fanconi anemia is an inherited disorder that is characterized by an inability to repair DNA damage. Most patients will experience bone marrow failure, requiring stem cell transplantation. Conditioning agents to clear space for engraftment and prevent immunologic rejection often leads to toxic side effects and subsequent cancers. Pre-clinical data suggest that in-utero hematopoietic stem cell transplantation without conditioning can circumvent the need for these agents. Although FA patients can be diagnosed prenatally, family preferences vary, and no systematic study of attitudes toward prenatal intervention in the FA community has previously been performed.
• What does this study add?
  • Our study demonstrates varying attitudes within the Fanconi anemia community toward prenatal interventions with a strong interest in in-utero therapies which are likely to be clinically available in the near term.

ファンコニ貧血に対する子宮内造血幹細胞移植 In utero hematopoietic stem cell transplantation for Fanconi anemia

Leah Swartzrock,Carla Dib,Morgane Denis,Hana Willner,Katie Ho,Ethan Haslett,Jian Han,Wenjing Pan,Miranda Byrne-Steele,Brittany Brown,Mark R. Krampf,Anna Girsen,Yair J. Blumenfeld,Yasser Y. El-Sayed,Maria G. Roncarolo,Tippi C. MacKenzie,Agnieszka D. Czechowicz
Blood Advances  Published:August 29, 2024
DOI:https://doi.org/10.1182/bloodadvances.2023011894

TO THE EDITOR

Fanconi anemia (FA) is a grievous inherited DNA repair disorder resulting in the inability to repair interstrand crosslinks.^1,2 FA is caused by mutations in 1 of 23 different FA complementation (FANC) genes, with the most frequent mutations occurring in FANCA (∼60%-70%), FANCC (∼10%), and FANCG (∼10%).³ The increased chromosomal fragility in FA individuals leads to progressive bone marrow failure (BMF) and a systemic predisposition to malignancies. Almost all patients with FA develop BMF by young adulthood with ∼80% developing BMF by age 10 years.^1,3 Additionally, all patients with FA have a high risk of developing acute myeloid leukemia and myelodysplastic syndrome throughout their lives.^1,4 The only proven curative treatment for these hematologic diseases is allogeneic hematopoietic stem cell transplantation (HSCT), which is required for patients with FA who have developed BMF, myelodysplastic syndrome, and acute myeloid leukemia.⁵ However, the efficacy of postnatal HSCT is often complicated by the availability of HLA-matched donors, graft-versus-host disease (GVHD), and graft rejection.⁵ Further, the conditioning used pre-HSCT, which includes immune suppression and genotoxic chemotherapy and/or total body irradiation, poses significant comorbidity to patients with FA because it causes direct tissue injury leading to organ damage and infertility, predisposes patients to deadly infections, and increases likelihood of malignancies in these patients with hypersensitivity leading to incurable solid tumors in early adulthood in almost all patients after current HSCT.^5-7 Autologous lentiviral HSC-based gene therapy is being developed as an alternative to postnatal allogeneic HSCT, which could enable preventive treatment of hematologic disease in patients with FA. However, this is challenged by the need for unique treatments for each FA complementation group, potential problematic lentiviral integration, continued risk of malignancies, and the significant resources required for personalized treatments.^8,9 Early prenatal intervention via in utero (allogeneic) HSC transplantation (IUHSCT) into a FA gestational fetus may be an avenue to overcome limitations of postnatal HSCT and gene therapy: stabilizing hematopoiesis before the onset of hematologic symptoms and providing an effective intervention for all FA subtypes. Unique fetal tolerance of maternal antigens has also been observed in the prenatal setting partially due to deletion of alloreactive effector T cells.^10-12 Thus, IUHSCT could potentially be conducted without any pre-HSCT conditioning, thereby eliminating current life-threatening treatment regimens.