Our Science

Gene modified hematopoietic stem and progenitor cell (HSPC) therapy is a commercially proven approach for disease modifying and potentially curative treatments in certain inherited disorders.

Published studies by scientific founder, Dr. Cherqui, demonstrate multi-systemic engraftment and functional rescue utilizing our gene modified HSPCs for Friedreich's ataxia, Danon disease, and Alzheimer’s disease.

Our Pipeline

Featured Publication:

(2024) Gene editing improves endoplasmic reticulum-mitochondrial contacts and unfolded protein response in Friedreich’s ataxia iPSC-derived neurons. Front. Pharmacol. Volume 15.

FXN corrected hspc

Our lead preclinical program (PPL-001) is a gene modified hematopoietic stem and progenitor cell (HSPC) designed to correct the mutation located in the FXN gene of patients with Friedreich's ataxia.

Our approach aims to address the underlying cause of the condition through correction of the GAA repeat expansion in the FXN Intron 1, yielding an HSPC that delivers normal levels of functional Frataxin protein throught the body.

Sivakumar A, Cherqui S (2022) Advantages and Limitations of Gene Therapy and Gene Editing for Friedreich’s Ataxia. Front. Genome Ed. 4:903139.

SELECTED PUBLICATIONS

(2024) Mishra P, Sivakumar A, Johnson A, Pernaci C, Warden AS, El-Hachem LR, Hansen E, Badell-Grau RA, Khare V, Ramirez G, Gillette S, Solis AB, Guo P, Coufal N, Cherqui S. Gene editing improves endoplasmic reticulum-mitochondrial contacts and unfolded protein response in Friedreich’s ataxia iPSC-derived neurons. Front. Pharmacol. Volume 15.

(2023) Mishra P, Silva A, Sharma J, Nguyen J, Pizzo DP, Hinz D, Sahoo D, Cherqui S. Rescue of Alzheimer’s disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cells. Cell Reports. 42 (8); 112956.

(2022) Sivakumar A and Cherqui S. Advantages and limitations of gene therapy and gene editing for Friedreich’s ataxia. Frontiers in Genome Editing. Review.

(2020) Rocca CJ, Rainaldi JN, Sharma J, Shi Y, Haquang JH, Luebeck J, Mali P, Cherqui S. CRISPR/Cas9 gene editing of hematopoietic stem cells from patients with Friedreich’s ataxia. Mol Ther Methods Clin Dev. 17:1026-1036.

(2020) Manso AM, Hashem S, Nelson BC, Gault E, Soto-Hermida A, Villarruel E, Brambatti M, Bogomolovas J, Bushway PJ, Chen C, Battiprolu P, Keravala A, Schwartz JD, Shah G, Gu Y, Dalton ND, Hammond K, Peterson K, Saftig P, Adler ED. Systemic AAV9.LAMP2B injection reverses metabolic and physiologic multiorgan dysfunction in a murine model of Danon disease. Sci Transl Med. 12(535).

(2019) Goodman S, Naphade S, Khan M, Sharma J, Cherqui S. Macrophage polarization impacts tunneling nanotube formation and intercellular organelle trafficking. Sci Rep. ;9(1):14529.

(2017) Rocca CJ, Goodman SM, Dulin JN, Haquang JH, Gertsman I, Blondelle J, Smith JLM, Heyser CJ, Cherqui S. Hematopoietic stem cell transplantation prevents development of Friedreich’s Ataxia in a humanized mouse model. Sci Transl Med. 9(413).

(2017) Cherqui S & Courtoy PJ. The renal Fanconi syndrome in cystinosis: pathogenic insights and therapeutic perspectives. Nature Reviews Nephrology volume 13, 115–131.

(2017) Hashem SI, Perry CN, Bauer M, Han S, Clegg SD, Ouyang K, Deacon DC, Spinharney M, Panopoulos AD, Izpisua Belmonte JC, Frazer KA, Chen J, Gong Q, Zhou Z, Chi NC, Adler ED. Impaired mitophagy facilitates mitochondrial damage in Danon disease. Journal of Molecular and Cellular Cardiology. 108:86-94.

(2016) Gaide Chevronnay HP, Jansen V, Van Der Smissen P, Rocca CJ, Liao XH, Refetoff S, Pierreux CE, Cherqui S & Courtoy P. Hematopoietic stem cell transplantation can normalize thyroid function in a cystinosis mouse model. Endocrinology. 57(4):1363-1371.

(2015) Naphade S, Sharma J, Gaide Chevronnay HP, Shook MA, Yeagy BA, Rocca CJ, Ur SN, Lau AJ, Courtoy PJ, Cherqui S. Lysosomal cross-correction by hematopoietic stem cell-derived macrophages via tunneling nanotubes. Stem Cells. 33(1):301-309.

(2015) Hashem SI, Perry CN, Bauer M, Han S, Clegg SD, Ouyang K, Deacon DC, Spinharney M, Panopoulos AD, Izpisua Belmonte JC, Frazer KA, Chen J, Gong Q, Zhou Z, Chi NC, Adler ED. Oxidative Stress Mediates Cardiomyocyte Apoptosis in a Human Model of Danon Disease and Heart Failure. Stem Cells. 33(7):2343-50.

(2013) Harrison F, Yeagy BA, Rocca CJ, Kohn DB, Salomon DR, Cherqui S. Hematopoietic stem cell gene therapy in the mouse model of cystinosis. Molecular Therapy. Mol Ther. 21(2):433-444.