Hematopoietic Stem Cells – VJRegenMed

Novel gene therapies for metachromatic leukodystrophy

Simon Ng — Thu, 03 Mar 2022 17:46:25 +0000

Kent Christopherson, PhD, Orchard Therapeutics, Boston, MA, describes the development and mechanism of action of atidarsagene autotemcel, a gene therapy consisting of an autologous CD34⁺ cell enriched population that contains hematopoietic stem and progenitor cells (HSPC) transduced using a lentiviral vector. The gene therapy, which has been approved in the EU, aims to treat metachromatic leukodystrophy (MLD) and the vector encodes the human arylsulfatase-A (ARSA) gene, which is faulty in patients with MLD. HSPC cells with the functional gene can subsequently produce the correct protein, which can be trafficked and permanently integrated in the central nervous system (CNS). This interview took place at Advanced Therapies Week 2022.

Key developments in the future of advanced therapies

Simon Ng — Tue, 01 Feb 2022 18:03:39 +0000

Lavakumar Karyampudi, PhD, Moffitt Cancer Center, Tampa, FL, provides an overview of the topics discussed during the session on cell and gene therapies of the future at Advanced Therapies Week 2022. Dr Karyampudi highlights the development of hematopoietic stem cell gene therapy for rare disease, optimizing the yield of lentiviral vectors for gene therapies, as well as strategies to decrease manufacturing times in the production of cell and gene therapies. This interview took place at Advanced Therapies Week 2022.

RP-L301 lentiviral gene therapy for PKD

admin_vjr_user — Mon, 27 Dec 2021 12:22:59 +0000

Jose-Luis López-Lorenzo, MD, University Hospital Jimenez Diaz, Madrid, Spain, describes ongoing research into RP-L301, an investigational lentiviral gene therapy for pyruvate kinase deficiency (PKD). This approach involves autologous hematopoietic stem cells being transduced ex vivo with a lentiviral vector carrying a functional copy of the deficient PKLR gene. Based on preclinical studies in a murine model of PKD, a Phase I clinical trial (NCT04105166) evaluating RP-L301 is currently underway. While results obtained from two patients treated so far are promising, Dr López-Lorenzo notes that data from the treatment of more patients with a longer follow-up time is needed and highlights the need for a less complex and safer treatment protocol in the future. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

An update on the Phase I trial evaluating RP-L301 in PKD

admin_vjr_user — Mon, 27 Dec 2021 12:22:57 +0000

Jose-Luis López-Lorenzo, MD, University Hospital Jimenez Diaz, Madrid, Spain, provides an update on a Phase I clinical trial (NCT04105166) evaluating the safety of RP-L301, an investigational lentiviral gene therapy, in patients with pyruvate kinase deficiency (PKD). Dr López-Lorenzo outlines the study design, which involves the collection of peripheral blood hematopoietic stem cells (HSCs) which are transduced with a lentiviral vector carrying a functional copy of the deficient PKLR gene. Patients then receive a busulfan-containing conditioning regimen and then intravenous infusion of the RP-L301 HSC product. In the first two patients treated, hemoglobin levels were restored to normal levels, both report improved quality of life and no serious adverse events have been attributed to RP-L301. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

Gene therapy for PKD: addressing the unmet clinical need

admin_vjr_user — Mon, 27 Dec 2021 11:13:30 +0000

Jose-Luis López-Lorenzo, MD, University Hospital Jimenez Diaz, Madrid, Spain, describes the therapeutic landscape for pyruvate kinase deficiency (PKD), a rare inherited hemolytic anemia caused by mutations in the PKLR gene. Treatment of PKD is currently largely limited to blood transfusion, chelation therapy and splenectomy, which are associated with significant side effects. Dr López-Lorenzo discusses the rationale behind the development of gene therapies for PKD, such as the transplantation of autologous hematopoietic stem cells containing a functional copy of the deficient PKLR gene. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

The role of hematopoietic stem cells in regenerative medicine

Simon Ng — Wed, 22 Dec 2021 10:32:56 +0000

Ira Espuny-Camacho, PhD, University of Liège, Liège, Belgium, discusses using hematopoietic stem cells (HSCs) in disease models and clinical therapies. She highlights how human stem cell-based models may yield more accurate data and lead to more efficacious therapies than current animal models. Therapies based on HSCs additionally have many advantages, as they can be easily mass-produced and can differentiate into various cell types such as cardiomyocytes and retinal pigment epithelia for different indications. This interview took place at the 6th World Congress of the Tissue Engineering and Regenerative Medicine International Society (TERMIS 2021).

Identifying issues associated with HSCs

Simon Ng — Wed, 22 Dec 2021 10:32:54 +0000

Ira Espuny-Camacho, PhD, University of Liège, Liège, Belgium, provides an overview of potential challenges in using hematopoietic stem cells (HSCs). Whilst HSCs can be easily manufactured and are versatile, HSCs derived from embryonic stem cells pose a problem due to ethical concerns. The risk of tumorigenesis as a result of epigenetic instability and immunogenicity are additional issues that need to be overcome, where developing autologous HSC-based therapies will be especially advantageous compared to allogeneic therapies. This interview took place at the 6th World Congress of the Tissue Engineering and Regenerative Medicine International Society (TERMIS 2021).

Applications of brain organoids in neurology

Simon Ng — Wed, 22 Dec 2021 10:32:52 +0000

Ira Espuny-Camacho, PhD, University of Liège, Liège, Belgium, describes the development of brain organoids as disease models. Organoids formed from hematopoietic stem cells (HSCs) can mimic the 3D architecture of the brain and can provide an insight into cortical development without any external stimuli. Using brain organoids can subsequently serve as models for neurodevelopmental and neurodegenerative diseases. This interview took place at the 6th World Congress of the Tissue Engineering and Regenerative Medicine International Society (TERMIS 2021).

HSC gene editing: current approaches and remaining challenges

admin_vjr_user — Thu, 19 Aug 2021 11:17:13 +0000

Valentina Vavassori, PhD, IRCCS San Raffaele Scientific Institute & Vita-Salute San Raffaele University, Milan, Italy, provides an overview of the current landscape for hematopoietic stem cell (HSC) gene editing and describes key gene editing approaches used including the non-homologous end joining (NHEJ) and homology-directed repair (HDR) pathways. Key lines of ongoing research to advance HSC gene editing approaches include the improvement of HDR efficiency in HSCs, as well as the development of new tools, such as CRISPR-associated transposases, to circumvent toxicity associated with double-strand breaks. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

T cell and HSC gene editing for the treatment of Hyper-IgM Type 1

admin_vjr_user — Wed, 18 Aug 2021 16:32:44 +0000

Valentina Vavassori, PhD, IRCCS San Raffaele Scientific Institute & Vita-Salute San Raffaele University, Milan, Italy, describes a gene editing approach under investigation for the treatment of hyper IgM Type 1 (HIGM1), an immunodeficiency disorder caused by mutations in the gene for CD40L, a T-cell surface molecule. The strategy involves the insertion of a 5’-truncated corrective CD40L cDNA into the native gene, which restores gene function and maintains the physiological regulation of the gene. This editing strategy was applied to both autologous T cells and hematopoietic stem cells (HSCs), which were then transplanted into mouse models to compare therapeutic efficacy of the two cell types. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.