Infusion of memory T-cells in COVID19 disease

Infusion of memory T-cells in COVID19 disease

The severe acute respiratory syndrome caused by the coronavirus 2 (SARS-CoV-2) emerged in December 2019 causing a global pandemic. COVID-19 progression is generally biphasic, initially viral and afterwards inflammatory.

La Paz University Hospital of Madrid previously reported the existence of a SARS-CoV-2 specific T cell population within the CD45RA memory T cells from the blood of convalescent donors. These cells can be stored and be immediately available as an “off-the-shelf” COVID-19 convalescent donor-derived biobank.

With the aim of determining the safety of a single infusion of memory T cells from a healthy donor recovered from COVID-19, evaluating time to lymphopenia recovery and to immune dysregulation, the time needed for a negative SARS-CoV-2 result by PCR, clinical improvement through the NEWS and a 7-category point ordinal scale, and length of stay, they set up a Phase I dose-escalation single centre clinical trial with 10 patients whose name was RELEASE and was published by The Lancet on August 12, 2021 with the collaboration of Geistek Pharmaceuticals.

 https://doi.org/10.1016/j.eclinm.2021.101086

No adverse events including transfusion-related acute lung injury (TRALI), cytokine release syndrome (CRS), graft-versus-host disease (GvHD), fever, or sudden respiratory failure were observed. Therefore, DLT was not identified with doses up to 1 × 106 cells/Kg and the maximum tolerated doses (MTD) were not reached.

All participants sustained recovery after 28 days of follow-up, and no allogeneic toxic effect were reported using memory (CD45RA) lymphocytes. No general adverse effects associated with the cryopreserved cell product in DMSO such as nausea, vomiting or abdominal cramps were observed.

They observed an improvement in clinical parameters measured by NEWS and 7-point scale two weeks post-infusion in both scales. Remarkable, patients with medium and high NEWS score at screening presented an improvement in the score to low risk and medium risk, respectively, at day 2 after infusion.

If you want to know more about this study, you can find it at https://doi.org/10.1016/j.eclinm.2021.101086

Infusion of memory T-cells in COVID19 disease

Infusion of memory T-cells in COVID19 disease

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Infusion of memory T-cells in COVID19 disease

The severe acute respiratory syndrome caused by the coronavirus 2 (SARS-CoV-2) emerged in December 2019 causing a global pandemic. COVID-19 progression is generally biphasic, initially

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Homocystinuria

Classic homocystinuria due to cystationine beta synthase deficiency is an autosomal recessive disease that affects 1 to 9 of every 100,000 newborns, but is detected

Homocystinuria

Classic homocystinuria due to cystationine beta synthase deficiency is an autosomal recessive disease that affects 1 to 9 of every 100,000 newborns, but is detected in only 1 of every 344,000. In recent years, the incidence of this disease is rising notably, causing that in some areas of the planet it is found in 1 in every 20,000 children. This important increase is causing the number of studies that are carried out on this disease to be increasing notably. The first investigations published in PubMed date back to 1963, with 3 articles while, today, more than 80 research articles are published per year, the most recent being on the use of liver transplantation as an effective treatment in patients with classic homocystinuria , or on obsessive-compulsive behaviors in these patients as a pathognomonic manifestation.

The disease is diagnosed through 3 types of tests:

  1. Analysis of amino acids in blood, including total homocysteine.
  2. Evaluation of the enzymatic activity of the CBS enzyme.
  3. Screening for mutations in the CBS gene (21q22.3).

The characteristics that these patients present are:

  1. Ocular system: ectopia lentis and severe myopia.
  2. Musculoskeletal system: genu valgum, pes cavus, dolicostenomelia, pectus excavatum or carinatum, kyphosis or scoliosis, and osteoporosis.
  3. Nervous system: psychiatric disorders, such as obsessive-compulsive disorder, have been detected in 51% of patients. They also have mental retardation that does not usually appear before 2 years of age.
  4. Cardiovascular system: thromboembolic events that are the cause of death in a large part of patients with this condition.
  5. Others: skin, liver and capillary alterations.

The treatments that exist today for this pathology are of 2 types depending on the type of patient, and it is always recommended that it be diagnosed at birth:

  1. Pyridoxine-responding patients: it is based on the administration in pharmacological doses of vitamin B6, B9 and B12.
  2. Non-responders to pyridoxine: the patient should have a diet low in methionine and rich in cystine, in combination with vitamins B6, B9 and B12. In addition, in 2007, anhydrous betaine received marketing authorization as an orphan drug, which is used to lower homocysteine ​​levels in patients not responding to pyridoxine (vitamin B6).

Effect of vitamins B6, B9 and B12 on homocysteine plasma decrease. https://www.nejm.org/doi/full/10.1056/nejmoa060900

To date, there is only one clinical trial that is recruiting patients in the world. This is the NCT03406611 trial and it proposes using the drug OT-58 as a new system for the enzymatic replacement of CBS. The results are expected for December 2021, and through this blog, we will publish them so that families and patients can know as quickly as possible what the results have been.

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Infusion of memory T-cells in COVID19 disease

The severe acute respiratory syndrome caused by the coronavirus 2 (SARS-CoV-2) emerged in December 2019 causing a global pandemic. COVID-19 progression is generally biphasic, initially

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Homocystinuria

Classic homocystinuria due to cystationine beta synthase deficiency is an autosomal recessive disease that affects 1 to 9 of every 100,000 newborns, but is detected

S4B: new therapeutic alternative for stroke

S4B: new therapeutic alternative for stroke

Advanced therapies are regulated in Spain by the RD 477/2014 and represent a great therapeutic opportunity for many patients with rare, serious or terminal diseases. One of these therapies has been developed in Spain in the Silk Biomed SL biotechnological laboratory. This company is a Spin-Off of the Polytechnic University of Madrid and today, it is completing the preclinical trials of its S4B therapy, a combination of a biomaterial with mesenchymal stem cells.

Its CEO, Fivos Panetsos, says that it is an innovative way to help the recovery of patients affected by this type of stroke, since silk fibroin is used with the aim of generating a gel that acts as a vehicle for cells and allow both, its protection of the immune system and its retention in the place of action. In this way, these cells, through their secretome, stimulate cell regeneration in the affected area, while protecting against further damage.

It is observed how there is a greater degree of fixation and survival of the cells of S4B therapy, compared to the classic techniques of intracerebral administration of stem cells.

This type of therapy is included in the group of combined drugs, that consist of an inert phase, silk fibroin, and a biological phase, mesenchymal stem cells. This innovative formulation has shown that it generates pores in its gel form that are small enough so that the immune system cannot enter to destroy them, but neither can the stem cells escape, so the fibroin would act as a fixative and protector of the stem cells. On the other hand, it is widely proven that silk fibroin is absolutely harmless for humans and does not generate any type of immune reaction, in addition to being totally biodegradable.

Comparación del uso de células madre sin fibroína de seda, y el uso de la terapia S4B en la recuperación de la actividad motora de los animales participantes en los estudios preclínicos.  

Comparison of the use of stem cells without silk fibroin, and the use of S4B therapy in the recovery of motor activity in animals participating in preclinical studies.
 

It has also been seen in preclinical studies developed by biotechnology, that the pro-inflammatory cytokines released in the affected area, such as tumor necrosis factor alpha, activate these cells so that they begin to produce their secretome, in which they are found. molecules such as transforming growth factor beta, which induces the regeneration of the affected area, as well as a series of anti-inflammatory and neuroprotective molecules that will promote the recovery of the patient.

At Geistek Pharmaceuticals, we are in charge of designing and leading the clinical trial of S4B therapy which, in a short period of time, will begin its safety phase.,

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Infusion of memory T-cells in COVID19 disease

The severe acute respiratory syndrome caused by the coronavirus 2 (SARS-CoV-2) emerged in December 2019 causing a global pandemic. COVID-19 progression is generally biphasic, initially

Uncategorized

Homocystinuria

Classic homocystinuria due to cystationine beta synthase deficiency is an autosomal recessive disease that affects 1 to 9 of every 100,000 newborns, but is detected