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

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.

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.

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.