Clinical trials of Fisetin in a person with autoimmune thyroiditis
Organisation: IntraClear Initiative
Supervisor: Ariel Feinerman
Medical advisor: Alexander Morozov
In recent years, clinical trials of drugs that affect extracellular and intracellular damage leading to ageing of the body have begun. You can find more info here [1].
For example, with age, senescent cells accumulate in our body. They cannot perform their functions normally, their abnormal metabolism is the cause of chronic inflammation, which plays an important role in ageing.
Relatively recently, senolitics, substances that selectively induce apoptosis (lead to programmed death) of senescent cells, have begun to be studied. Their studies have shown that when senescent cells are destroyed in old mice, they begin to look younger, and the function of their body improves.
In these studies, senolytic drugs have restored exercise capacity and capacity to form new blood and immune precursor cells in ageing mice to near youthful norms, while preventing age-related lung hypofunction, fatty infiltration into the liver, weakening or failure of the heart, osteoporosis, and hair loss. These treatments have also prevented or treated mouse models of diseases of ageing like osteoarthritis, fibrotic lung disease, nonalcoholic fatty liver disease (NAFLD), atherosclerosis, cancer and the side-effects of conventional chemotherapy, as well as neurodegenerative diseases of ageing like Parkinson’s and Alzheimer’s [2]!
Since senescent cells also arise in the immune system, being one of the causes of autoimmune diseases, there is a hypothesis that the destruction of senescent cells will help in the prevention and treatment of many autoimmune diseases.
It is important that the mechanisms of cell senescence and the effects of their destruction by senolitics are similar in mice and humans. For example, it has been shown that the combination of dasatinib (a relatively aggressive chemotherapeutics) and quercetin (flavonoid) works in humans as well as in mice when it comes to destruction of senescent cells [3].
Some drugs that have established senolytic effects are available for purchase just now. However, they are usually used in much lower dosages than is required for the senolytic effect. Such substances include the readily available and cheap bioactive flavonoid fisetin.
Mice experiments show that fisetin is about as effective against senescent cells as the dasatinib + quercetin combination. The advantage of fisetin, which is a plant substance, is its safety compared to many other drugs that have shown a senolytic effect [4].
There are currently three clinical trials in humans. They are conducted in Mayo Clinic (USA), where a special treatment protocol was developed. Mayo Protocol consists in taking 20 mg / kg of fisetin orally for two days in a row, after which a person takes the second course after a month or two months [5].
Clinical Trials at Mayo Clinic
Institute |
Date |
Title |
Diseases |
Participants |
Dose |
Duration |
Main results |
Primary outcome measures |
Mayo Clinic |
Study Start Date: November 15, 2018 Estimated Study Completion Date: April 28, 2020 |
Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Adults |
Frail Elderly Syndrome Phase 2 |
40; age 70-90; Male and Female |
20 mg/kg/day, orally |
2 consecutive days |
No results reported yet |
Percent decrease in blood inflammation markers (7 days) |
Mayo Clinic |
Study Start Date: February 6, 2018 Estimated Study Completion Date: |
Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Women |
Frail Elderly Syndrome Phase 2 |
40; age 70-90; Female |
20 mg/kg/day, orally |
2 consecutive days, for 2 consecutive months |
No results reported yet |
Improved 6-minute walk (time frame: one month) Improved gait speed |
Mayo Clinic |
Actual Study Start Date: January 2, 2018 Estimated Study Completion Date: |
Inflammation and Stem Cells in Diabetic and Chronic Kidney Disease |
Chronic Kidney Diseases; |
30; age 40-80; Male and Female |
20 mg/kg/day, orally |
2 consecutive days |
No results reported yet |
Change in inflammatory markers including C-reactive protein (14 days) in the skin, fat, plasma, and urine measured at baseline and day 14 Effect on mesenchymal stem cell function including cell migration measured at baseline and day 14 |
Because of the availability and safety of fisetin, we decided to conduct our own clinical trials of this drug in a person with autoimmune thyroiditis. It is noteworthy that, unlike most tests, we focus not on chronic inflammation, but on immune function.
Patient information
Name | Sex | Age | Chronic diseases | Treatments |
Anonymous | M | 34 | Autoimmune thyroiditis,
Hypothyroidism, Sinus tachycardia, Raynaud’s syndrome (?) Fibromyalgia (?) |
Concor, 2,5 mg,
Euthyrox, 75 mg
|
Before taking fisetin, we will determine the biochemical parameters of the functions of various organs and systems, focusing on the chronic inflammation and immune function. After the course of taking fisetin, we will repeat the study. The subjective sensations of a person will also be recorded.
If the experiment shows success, it will lay the basis for a large-scale clinical trial and will open up prospects for the prevention and treatment of autoimmune diseases.
For these tests, we need your financial help. For measurements, $1,054 are needed, of which $110 were collected, and $944 are still needed.
You can help via PalPal arielfeinerman@gmail.com or form
Primary measures
Date | Test | Result | Limits | Price |
Immunology | ||||
Full immune status | $73 | |||
CD3+ lymphocytes | ||||
CD4+ lymphocytes | ||||
CD8+ lymphocytes | ||||
CD19+ lymphocytes | ||||
CD20+ lymphocytes | ||||
CD16+/CD56+ lymphocytes | ||||
CD25+ lymphocytes | ||||
HLA DR+/- lymphocytes | ||||
IgA | $3 | |||
IgM | $3 | |||
IgG | $3 | |||
IgE | $3 | |||
Circulating immune complexes | $4 | |||
Phagocytic activity of peripheral blood leukocytes | $4 | |||
Antibodies for antigens of plant, animal and chemical origin | $37 | |||
Antinuclear antibodies, immunoblot (autoantibodies IgG
for 14 various antigens: nRNP/Sm, Sm, SS-A (SS-A native and Ro-52), SS-B, Scl-70, Jo-1, PM-Scl, centromere protein B, PCNA, dsDNA, nucleosomes, histones, ribosomal protein P, AMA-M2) |
$78 | |||
ACCP | $15 | |||
ELI-viscero-24 | $78 | |||
Clinical blood tests | ||||
Сomplete blood count with differential interpretation | $4 | |||
Biochemistry | ||||
Biochemical blood assay | $47 | |||
Total protein | ||||
Blood urea nitrogen (BUN) | ||||
Creatinine | ||||
Uric acid | ||||
Total bilirubin | ||||
Direct bilirubin | ||||
Alanine Aminotransferase (ALT) | ||||
Aspartate Aminotransferase (AST) | ||||
Alkaline Phosphatase (ALP) | ||||
Lipase | ||||
Gamma-Glutamyl Transferase (GGT) | ||||
Iron | ||||
Total Cholesterol | ||||
Triglycerides | ||||
Na/K/Cl | ||||
Total Calcium | ||||
Blood Glucose | ||||
C-reactive Protein | ||||
Rheumatoid Factor (RF) | ||||
Pituitary hormones and pituitary-adrenal system | ||||
Adrenocorticotropic Hormone (ACTH) | $13 | |||
Cortisol | $6 | |||
Chondrotropic hormone | $10 | |||
Insulin-like Growth Factor-1 (IGF-1) | $14 | |||
Blood catecholamines (adrenaline, norepinephrine, dopamine) and
serotonin |
$38 | |||
Thyroid function | ||||
Thyroid-stimulating Hormone (TSH) | $5 | |||
T4 Free | $5 | |||
T3 Free | $5 | |||
Thyroglobulin Antibody | $6 | |||
Thyroid Peroxidase Antibody | $6 | |||
Thyroglobulin | $6 | |||
Chronic inflammation | ||||
IL-6 | $30 | |||
IL-8 | $30 | |||
High-sensitivity C-reactive Protein (hs-CRP) | $4 | |||
Enzymes | ||||
Amylase | $2 | |||
Total | $527 |
Stay tuned for future trial information with the Future Collector!
Links
1. Steve Hill, Nicola Bagalà, The First Rejuvenation Therapy Reaches Human Trials.
2. Michael Rae, Senolytics – Solution or Self-Defeating for Senescent Cells?
3. Hickson LJ, Langhi Prata LGP, Bobart SA, Evans TK, Giorgadze N, Hashmi SK, Herrmann SM, Jensen MD, Jia Q, Jordan KL, Kellogg TA, Khosla S, Koerber DM, Lagnado AB, Lawson DK, LeBrasseur NK, Lerman LO, McDonald KM, McKenzie TJ, Passos JF, Pignolo RJ, Pirtskhalava T, Saadiq IM, Schaefer KK, Textor SC, Victorelli SG, Volkman TL, Xue A, Wentworth MA, Wissler Gerdes EO, Zhu Y, Tchkonia T, Kirkland JL. Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine. 2019 Sep;47:446-456. doi: 1016/j.ebiom.2019.08.069. Epub 2019 Sep 18. PubMed PMID: 31542391.
4. Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, Ling YY, Melos KI, Pirtskhalava T, Inman CL, McGuckian C, Wade EA, Kato JI, Grassi D, Wentworth M, Burd CE, Arriaga EA, Ladiges WL, Tchkonia T, Kirkland JL, Robbins PD, Niedernhofer LJ. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018 Oct;36:18-28. doi: 1016/j.ebiom.2018.09.015. Epub 2018 Sep 29. PubMed PMID: 30279143; PubMed Central PMCID: PMC6197652.
5. Cari Green, Michael Greve, Fisetin Senolytic Therapy