|
|
Post by itellthefuture777 on Jun 10, 2021 9:01:39 GMT -5
www.ncbi.nlm.nih.gov/pmc/articles/PMC7417114/Repurposing of Kinase Inhibitors for Treatment of COVID-19 Protein kinases have become an exceptionally important group of drug targets, accounting for 20-30% of the drug discovery programs of major pharmaceutical companies and are thus an opportune target. Many kinase inhibitors that have pharmacologic effects that may be beneficial in ameliorating the severe and potentially life-threatening symptoms of COVID-19, such as anti-inflammatory activity, cytokine suppression, and antifibrotic activity, are already approved. Ideally, one kinase inhibitor with optimal pharmacokinetic properties could be repurposed as a dual function therapeutic that could reduce infection through direct viral targeting and could also provide clinical benefit by suppressing disease symptoms. Alternatively, kinase inhibitors could be tested in combination with antiviral agents or other targeted therapies that show promise in clinical trials for COVID-19 to achieve greater efficacy than any one agent alone. Kinase inhibitors as potential antiviral therapeutics The fact that treatments for respiratory viral infections like those caused by SARS-CoV, MERS-CoV, and SARS-CoV-2 are restricted to medications designed to treat only symptoms of pulmonary disease justifies the repurposing of drugs, preferably FDA-approved drugs already investigated in patients for tolerance and toxicity, with the dual ability to target the root causes of infection and to mitigate symptoms of respiratory distress caused by the infection. It would thus be beneficial to find and identify multi-targeted drugs in clinical use that encompass both properties. Such drugs would ideally also be able to potentiate the effectiveness of other more targeted antiviral agents or supportive therapies approved for severe or potentially fatal respiratory diseases. A number of approved antiviral treatments are designed to inhibit enzymes such as polymerases or proteases through a “one drug, one bug” line of attack, which has been deemed inadequate due to the inefficiency of these treatments in working against multiple viruses, as well as failure to treat emerging new strains with accumulating mutations that are drug-resistant. The high cost and lengthy timeline for development of a novel agent are additional factors that dramatically limit the efficiency of this approach for covering a wide range of existing viruses as well as newly emerging ones or those that have developed resistance to current therapies. A different strategy involves targeting integral host cell proteins that are required by a broad spectrum of pathogens, including those that are emerging and novel and for which no effective treatment exists. An advantage of targeting host cellular proteins is that they do not undergo the same mutation rates that are seen for genomes of viruses.
|
|
|
|
Post by straightly on Jun 10, 2021 9:01:49 GMT -5
Exciting news 🥋☕️🤙 🥭 MannKind will conduct formulation and preclinical studies of a new chemical entity owned by Thirona 🥭 MannKind purchased a convertible note issued by Thirona 🥭 The transaction is intended to advance the development of a novel compound with potential for multiple indications 🥭 FBM5712 is a novel small molecule inhibitor of the ALK-5 kinase (the transforming growth factor-β (TGF-β) receptor kinase), which is being developed by Thirona as a topical product intended to prevent and/or reduce skin fibrosis. “TGF-β is also implicated in lung fibrotic diseases and ALK-5 has been validated as a potential target for idiopathic pulmonary fibrosis,” said Thomas Hofmann, M.D., Ph.D., Chief Scientific Officer of MannKind Corporation 🥭 MannKind will formulate FBM5712 as a dry powder formulation. If initial studies are promising, MannKind can exercise certain rights to seek a full license to the compound for clinical development and commercialization for the treatment of fibrotic pulmonary diseases 🥭 “We recently announced our goal of launching a new product from our pipeline every year between 2025 and 2030,” said Michael Castagna, PharmD, Chief Executive Officer of MannKind Corporation. “We are excited by the opportunity to evaluate FBM5712 and to assess its potential to support our pipeline ambitions.” |
|
|
|
Post by straightly on Jun 10, 2021 9:08:18 GMT -5
Am I reading too much into this or way ahead of my self? If this is a potential treatment for Cystic Fibrosis, it will be YUGE. CF is a generic disease without a cure and average life span of 28. Patients often required lung and other organ transplant and current treatment is composed of antibiotic cocktails with costs of tens of thousands per month.
|
|
|
|
Post by straightly on Jun 10, 2021 9:12:42 GMT -5
Am I reading too much into this or way ahead of my self? If this is a potential treatment for Cystic Fibrosis, it will be YUGE. CF is a generic disease without a cure and average life span of 28. Patients often required lung and other organ transplant and current treatment is composed of antibiotic cocktails with costs of tens of thousands per month. Diabetes, as bad as they are, are but just another relatively minor issue these patients have to deal with. |
|
|
|
Post by itellthefuture777 on Jun 10, 2021 9:15:03 GMT -5
This is an antifibrotic....being reviewed as a ...repurposed to Covid...
They also have Clofazimine...also anti Covid...and much more..hmm
|
|
|
|
Post by straightly on Jun 10, 2021 9:18:00 GMT -5
Am I reading too much into this or way ahead of my self? If this is a potential treatment for Cystic Fibrosis, it will be YUGE. CF is a generic disease without a cure and average life span of 28. Patients often required lung and other organ transplant and current treatment is composed of antibiotic cocktails with costs of tens of thousands per month. Diabetes, as bad as they are, are but just another relatively minor issue these patients have to deal with. The news release qualified as “tongue in check”, hinting CF but purposely avoid referencing it directly: IF it is effective against CF at all, it is too big to mention lightly. |
|
|
|
Post by neil36 on Jun 10, 2021 9:19:39 GMT -5
|
|
|
|
Post by straightly on Jun 10, 2021 9:29:17 GMT -5
Diabetes, as bad as they are, are but just another relatively minor issue these patients have to deal with. The news release qualified as “tongue in check”, hinting CF but purposely avoid referencing it directly: IF it is effective against CF at all, it is too big to mention lightly. With the very little of what I know of CF, one thing they will not be short of will be patients at end of life volunteering for the experiments, even very young patients. |
|
|
|
Post by itellthefuture777 on Jun 10, 2021 9:39:18 GMT -5
www.frontiersin.org/articles/10.3389/fmed.2020.00539/fullPutting Scarring and Lung Fibrosis Into Context Our perspective is that the survivors of post-viral ARDS recover with mild residual pulmonary deficits and that interventions to prevent these mild abnormalities are unnecessary during the COVID-19 pandemic. Despite overlapping pathways, the timing, etiology, prognosis, and mechanistic underpinnings of post-viral scarring are quite different than chronic fibrosing interstitial lung disease. IPF is progressive and eventually fatal in most patients (39). Pulmonary fibrosis secondary to autoimmune causes such as rheumatoid arthritis and scleroderma may similarly progress and can be treated with an approved anti-fibrotic therapy. Patients with connective tissue diseases who develop lung fibrosis have a relatively poor prognosis (40). In contrast, while post-inflammatory changes can be seen in some ARDS survivors, progressive fibrosis has not been an important characteristic in ARDS related to respiratory infections and viral pneumonias. Our recent understanding of the pauci-immune mechanism of IPF differs substantially from the intense inflammatory response noted in ARDS and viral pneumonias. Moreover, viral inflammation induces robust T cell responses that can persist for months (41). It is quite possible that a significant subset of patients with COVID-19 have ARDS physiology (or atypical ARDS with relatively normal lung compliance) due to high-intensity lymphocytic alveolitis. This contrasts with other causes of ARDS in which an intense neutrophilic alveolitis is the rule. Comparisons have been made between ARDS-related fibrosis in humans and the intense inflammation and scarring in the bleomycin mouse model, a model in which young mice resolve their fibrotic lung disease (42). Age and underlying lung diseases may be important risk factors for enhanced fibrotic responses following ARDS. In the late stages of ARDS, diffuse alveolar damage with excessive and abnormal deposition of extracellular collagen matrix predominates as a consequence of the known acute inflammatory insult. Interstitial and intra-alveolar fibrosis is often noted to varying degrees. The elevated levels of NT-PCP-III, which is derived from the cleavage of procollagen III, may be a useful biomarker to stratify therapies in critically ill patients with different phenotypes (43). Fibrosis from ARDS, in contrast to IPF, does not progress nor lead to a dominant pattern of honeycombing. Although the etiology of IPF remains obscure, the pathogenesis is best understood as a consequence of repetitive injuries followed by dysregulated repair processes, facilitated by telomere shortening, not intense inflammation (44–46). Discussion An excellent and thought-provoking review by George et al. highlights many nuances related to the care of IPF patients in the context of COVID-19 (7). Caring for patients with an underlying fibrotic lung disease is complex. The currently available anti-fibrotics have pleiotropic effects, allowing for many hypotheses related to their potential utility in other disease processes. It is clear that studies will proliferate as commercial interests grow and the pandemic continues in the absence of effective anti-virals and vaccines. The currently approved anti-fibrotics are meant for chronic disease management and by no means are curative nor do they reverse fibrosis. As such, despite the enthusiasm to study these medications, we believe that there is insufficient scientific rationale to do so, given the favorable course and the low prevalence of clinically meaningful scarring in survivors. The number of patients suffering from COVID-19 is accumulating and will be millions worldwide. Certainly we must evaluate patients, prospectively and retrospectively, to define the scope and the burden of residual pulmonary deficits and the fibrotic changes to determine their clinical significance. However, we find ourselves asking: Is it worth spending valuable time, resources, and scientific energy studying anti-fibrotic therapies in acutely ill, consent-weary patients that truly need a targeted antiviral treatment or trial? The responsible answer is “no.” Let us keep our focus during the pandemic. More to read on the link
|
|
|
|
Post by itellthefuture777 on Jun 10, 2021 9:49:21 GMT -5
Basically imo MNKD isn't going after the skin when making this into an inhaled dry powder version....so the "media" articles say
MannKind, Thirona to Study Treatment for Skin Fibrosis
Which..is misleading..imo
Clearly..fibrosis is found in the lungs of Covid patients that didn't make it...Mannkind again imo is targeting Covid...in the lung...not the external skin..
|
|
|
|
Post by Clement on Jun 10, 2021 10:07:35 GMT -5
mannkindcorp.com/pipeline says that MNKD-201 is for Idiopathic Pulmonary Fibrosis (IPF)
On Feb 26, mango posted:
"MNKD-201 for Idiopathic Pulmonary Fibrosis—what is it?
My guess? The Samumed small molecule that was specifically designed for inhalation for Idiopathic Pulmonary Fibrosis that targets the Wnt Pathway and was licensed to our partner, $UTHR"
At the time I thought that was a good guess. Now, I wonder. But mnkd might be taking a page from UTHR's book, ie, pursuing multiple treatments for the same indication at the same time.
|
|
|
|
Post by mango on Jun 10, 2021 12:03:59 GMT -5
mannkindcorp.com/pipeline says that MNKD-201 is for Idiopathic Pulmonary Fibrosis (IPF) On Feb 26, mango posted: "MNKD-201 for Idiopathic Pulmonary Fibrosis—what is it? My guess? The Samumed small molecule that was specifically designed for inhalation for Idiopathic Pulmonary Fibrosis that targets the Wnt Pathway and was licensed to our partner, $UTHR" At the time I thought that was a good guess. Now, I wonder. But mnkd might be taking a page from UTHR's book, ie, pursuing multiple treatments for the same indication at the same time. Yep, it could very well be this new chemical entity of Thirona’s and not the Samumed molecule owned by UT. Perhaps we will know for certain once they update the pipeline. I suspect you’re right and it is this new one with Thirona! |
|
|
|
Post by mytakeonit on Jun 10, 2021 13:18:03 GMT -5
This board is fabulous !!! I've learned more in the last few minutes ... then I did during my college years.
But, that's mytakeonit
|
|
|
|
Post by liane on Jun 10, 2021 14:13:44 GMT -5
What I'm thinking.... while the acute phase of the pandemic, and the need for vaccines and acute treatments will have a peak, the long-lasting effects in some patients will be here for a very long time. MNKD would be very wise to pursue treatment for the lung scarring and fibrosis as this will provide a recurring revenue stream.
|
|
|
|
Post by mymann on Jun 10, 2021 14:22:52 GMT -5
COVID play for Mannkind, infection causing diabetes and lung damage.
|
|
