Therapeutic Solutions International Inc (TSOI)

[cablejohn]

by TimGDixon » Thu Nov 24, 2022 6:15 am
https://forum.therapeuticsolutionsint.com/viewtopic.php?t=481
When Justia publishes I will replace the text.


LITHIUM AS A MONOTHERAPY AND/OR STEM CELL ADJUVANT THERAPY FOR PULMONARY FIBROSIS

Abstract
Disclosed are compositions of matter, therapeutics, and protocols useful for reduction and/or reversion of pulmonary fibrosis. In one specific embodiment lithium chloride is administered together with a regenerative cell in a patient suffering from, or at risk of pulmonary fibrosis. In one embodiment said lithium chloride is administered as an adjuvant to a regenerative therapy, wherein said regenerative therapy is a gene therapy, a protein therapy, a cell therapy, or a tissue transplant. In one embodiment lithium chloride, or a salt thereof is utilized alone, or with a regenerative means, to evoke preservation and/or elongation of telomere length in pulmonary tissue.

Background/Summary
CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 63/191,770 filed May 21, 2021, the entire contents of which is incorporated herein by reference.

FIELD OF THE INVENTION

[0002] The invention pertains to the treatment, prevention, or amelioration of pulmonary fibrosis, using lithium as a therapeutic agent whether by itself or as a regenerative cell adjuvant.

BACKGROUND

[0003] It is recognized that coronaviruses (CoVs) are a single stranded positive sense RNA viruses which include four genera (alpha, beta, delta, and gamma) [1]. Infectivity of CoVs is mediated by the envelope spike (S) glycoprotein which binds to its cellular receptors angiotensin-converting enzyme 2 (ACE2) and dipeptidyl peptidase 4 (DPP4) for SARS-CoV and MERS-CoV, respectively [2, 3]. In the case of the novel COVID-19 virus, it is over 99% similar to SAR-CoV-2 which is a new type of beta genera. This is based on 10 sequenced samples collected from the original location of the outbreak [4]. SAR-2-CoV preferentially infects the type 2 pulmonary epithelial cells, in the lungs, which express ACE2 [5]. Immune responses to the family of coronaviruses are associated with induction of type 1 interferons, especially interferon beta, which originally was termed “MSC interferon”. Clinical trials are ongoing assessing intranasal interferon beta (https://pharmaphorum.com/news/synairgen ... d-19-drug/) for COVID-19. Interferons not only induce expression of genes that block viral replication, but also are responsible for stimulating natural killer (NK) cells, which selectively kill virally infected cells. Interestingly, exogenous allogeneic NK cells have been recently cleared by FDA for treatment of COVID-19 (https://techcrunch.com/2020/04/02/ventu ... -covid-19/). One ideal treatment for prevention of SARS-CoV-2 progression would be an agent which induces interferon production in the lung.

[0004] Mortality from COVID-19 is caused by acute respiratory distress syndrome (ARDS) [6, 7], which is caused by unrestrained cytokine release, also known as “cytokine storm”, and is characterized by fluid leakage, diffuse inflammation, and disseminated intravascular coagulation, all of which cause impaired alveolar gas exchange. Approximately 35-45% of patients with ARDS will die [8].

[0005] The feasibility of utilizing cell based approaches to ARDS has been demonstrated in animal models [9-11], in which researchers have shown reduction of pulmonary injury, water leakage, and neutrophil accumulation. Furthermore, analysis of 342 systemic infusions and 57 bronchial instillations (204 recipients) of cells of various origins for ARDS and other pulmonary issues demonstrated safety in early clinical trials [12, 13].

[0006] Unfortunately, to date, no treatments appear effective for Post-COVID associated pulmonary fibrosis.