Shwe Parami Stroke Rehabilitation Clinic

21/01/2026

Today my patient

A 53 years old female stroke patient with right hemiparesis comes to take rehabitation treatment after 2 years of stroke attack.

On history, at first the patient felt sudden weakness of right side of body but she revovered within 2 days after sudden weakness of body.
At second time the patient got right hemiparesis after 6 months of first attack.
While she took treatments at the hospital and did rehabilitation exercises, she could not get recovery as first time attack.
The patient can walk by aiding some body or walking stick and can raise right hand up to head

The patient has no history of hypertension diabete and heart disease except family histoty of stroke.

Stroke rehabilitation timeline:
The most significant functional gains occurring in the first 3–6 months post-stroke. While recovery speeds slow after 6 months, improvement often continues for 18 months or more.

The patient can get gradual improvements through dedicated, ongoing therapy by using multiple vitamin B12 injections near the nerve at limbs and body sites on affected side followed by daily physical exercises.

Vitamin B12 injections near the nerve on affectef side that causes pain and movements of muscles via spinal reflex, those are learned by doing by brain because it mimics voluntarily
muscle movements.

Notes:
While involuntary, spinal reflexes are stereotyped, functional responses, such as contracting an agonist muscle and relaxing an antagonist muscle, which looks similar to a conscious movement.
That causes improvement of neural connection between muscle and brain and induction of neuroplasticity after stroke.

20/01/2026

The CRISPR-Cas9

CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9)

The system consists of two
main components, the Cas9 enzyme and a guide RNA (gRNA).
CRISPR-Cas9 guide RNA (gRNA) is a synthetic or engineered RNA molecule that directs the Cas9 nuclease to a specific 20-nucleotide target DNA sequence for gene editing.

CRISPR-Cas9 is a precise genetic engineering tool that uses a guide RNA (gRNA) to direct the Cas9 endonuclease to a specific DNA sequence, creating a double-strand break (DSB).

Composed of a crRNA (targeting sequence) and a tracrRNA (scaffold), it binds to Cas9, forming a ribonucleoprotein complex that creates double-strand breaks adjacent to a 5'-NGG-3' Protospacer Adjacent Motif (PAM).

A Protospacer Adjacent Motif (PAM) is a short, 2–6 base pair DNA sequence immediately following the target DNA (protospacer) that is essential for CRISPR-Cas system binding and cleavage.

Cas9 uses the PAM to rapidly scan the genome, binding only when the PAM is present, which significantly increases efficiency. If a designed guide RNA does not have a PAM sequence directly adjacent to it, the CRISPR system will not work.

gRNA can be a two-molecule system (crRNA + tracrRNA) or a single chimeric molecule known as single guide RNA (sgRNA).
Single guide RNA (sgRNA) is an engineered, chimeric RNA molecule used in CRISPR-Cas9 systems, merging crRNA (targeting) and tracrRNA (scaffold) into one single transcript.

Delivery
The Cas9-gRNA complex is introduced into the target cells (via viral vectors, plasmid transfection, or ribonucleoprotein delivery).

Mechanism
The 20-nucleotide sequence at the 5^prime end of the gRNA defines the target location through complementary base pairing.

Binding & Cleavage
The gRNA binds to the target DNA. Cas9 verifies the PAM sequence and cuts both strands of the DNA, typically 3 base pairs upstream of the PAM.

Repair & Editing:
Non-homologous end joining (NHEJ)(Knockout): The cell repairs the break by rapidly joining the ends, often causing small insertions or deletions (indels) that disable the gene.

Homology-directed repair (HDR) (Knock-in/Correction): If a repair template is introduced, the cell uses it to fix the break, allowing for the precise insertion of new genetic material.

Base editing and prime editing offer highly precise, double-strand break (DSB)-free genome modification, significantly reducing unintended insertions/deletions (indels) compared to traditional CRISPR-Cas9.

Applications of CRISPR-Cas9
Therapeutics: Treating genetic disorders by correcting mutations, and developing cancer immunotherapies (e.g., modifying T-cells).

Infectious Disease: Targeting and eliminating viral genomes, such as HIV, from infected cells.

Agricultural & Industrial: Creating disease-resistant crops, enhancing livestock, and developing efficient bacterial strains for bioindustrial production.

Research: Creating cellular and animal models to study gene function and disease mechanisms.

Advantages and Limitations
Advantages: Significantly faster, cheaper, and more accurate than previous gene-editing methods (e.g., ZFNs, TALENs).

Challenges: Potential for "off-target" effects, where unintended DNA sequences are cut, requiring refinement for safety in human clinical applications.

Ethics: The ability to modify human embryos has raised significant ethical debates regarding germline editing.

19/01/2026

CAR machropage (CAR-M)

The success of CAR-T therapies provides an excellent foundation for CAR-M development. CAR expression is expected to offer an additional stimulatory signal and redirect the immune effector functions of macrophages towards solid tumors.

CAR-macrophage (CAR-M) therapy is an emerging, promising immunotherapy that genetically engineers macrophages with chimeric antigen receptors (CARs) to actively target, phagocytose, and destroy tumor cells, particularly in solid tumors where CAR-T cells often struggle. CAR-Ms remodel the immunosuppressive tumor microenvironment, promote M1-like polarization, and stimulate broader, durable anti-tumor adaptive immunity.

Unlike CAR-T cells, which rely on cytotoxicity, CAR-macrophages are designed to phagocytose (engulf) solid tumor cells, acting as antigen-presenting cells that initiate adaptive immune responses.
Macrophages naturally infiltrate tumors, making them superior to T-cells in penetrating dense solid tumor environments.

Process and Mechanism
Cell Source and Manufacturing: Macrophages are derived from monocytes (PBMCs) collected from patients or donors, or via induced pluripotent stem cells (iPSCs) for "off-the-shelf" potential.
These cells are engineered to express CARs, often using viral vectors (like Ad5f35) or non-viral methods (like mRNA-LNPs).

CAR Structure and Signaling:
CAR-Ms typically feature an extracellular antigen-recognition domain (scFv), a hinge, and an intracellular domain. Key signaling domains like CD3ζ or FcRγ are used to trigger phagocytosis (similar to antibody-dependent cellular phagocytosis, ADCP).

Targeted Phagocytosis:
Upon recognizing specific antigens (e.g., HER2, Mesothelin, CD19) on tumor cells, the CAR-M engulfs and degrades the tumor cell.

Reprogramming the TME (M2 to M1 Shift): CAR-Ms are "locked" into a pro-inflammatory M1-like phenotype, allowing them to resist the immunosuppressive signals (M2) typical of the TME.

Antigen Presentation and Immune Activation: Beyond direct killing, CAR-Ms function as professional antigen-presenting cells (APCs). They process and present tumor antigens to T cells, activate them, and secrete pro-inflammatory cytokines (e.g., IL-12, TNF-α), which helps recruit other immune cells to the tumor site.

Advantages over CAR-T in Solid Tumors
Infiltration: Macrophages naturally migrate to tumors and can infiltrate dense, hypoxic solid tumor tissues better than T cells.

Lower Toxicity: Due to limited proliferation and shorter circulation times compared to T cells, CAR-Ms exhibit a safer profile with a lower risk of severe Cytokine Release Syndrome (CRS).

Epitope Spreading: By engulfing tumor debris and presenting new antigens, CAR-Ms can trigger a broader, long-lasting immune response against the tumor.

Challenges and Future Directions

Limited Persistence: Macrophages are terminally differentiated and do not proliferate after administration, which may require repeat dosing.

Manufacturing:
The process of differentiating and engineering macrophages is complex and costly, with ongoing efforts to develop "off-the-shelf" iPSC-derived CAR-Ms.

Combination Therapies: Researchers are combining CAR-Ms with checkpoint inhibitors (e.g., anti-PD-1) to further enhance their ability to overcome tumor evasion.

Early-phase clinical trials, such as the CARISMA Therapeutics trial (NCT04660929) using CT-0508, have shown that CAR-M therapy is safe, tolerable, and capable of remodeling the tumor microenvironment.

Chimeric antigen receptor macrophages (CAR-Ms) represent a promising frontier in immunotherapy, leveraging both innate and engineered capabilities to combat solid tumors. CAR-Ms can actively remodel the tumor microenvironment while directly targeting tumor cells through CAR signaling, making them a....

15/01/2026

NK Cell Therapy

NK cell therapy is an immunotherapy that boosts or utilizes natural killer (NK) cells—a type of white blood cell—to identify and destroy cancer cells and virally infected cells.
NK cell therapy involves isolating Natural Killer (NK) cells from a patient (autologous) or donor (allogeneic) via leukapheresis, expanding them ex vivo with cytokines (e.g., \(IL-2\), \(IL-15\)) to reach high numbers, and reinfusing the activated cells intravenously to target cancers. The process takes weeks, often includes quality testing, and can involve genetic engineering (CAR-NK) to improve tumor targeting.

Process
Isolation and Expansion
NK cells are collected from the patient (autologous) or donors (allogeneic) and cultured in a lab to significantly increase their numbers and potency.
Activation
The cells are activated, often using cytokines like interleukin-2 (IL-2), IL-12, IL-15, or IL-18, to enhance their ability to destroy tumor cells.
Infusion
The enhanced or engineered NK cells are infused back into the patient.

Advantages and applications
Dual Mechanism
NK cells destroy targets directly via toxic granules (perforin/granzymes) and by engaging with antibodies (ADCC - antibody-dependent cell-mediated cytotoxicity).
Antibody-dependent cellular cytotoxicity (ADCC) is an immune mechanism where antibodies (typically IgG) bind to antigens on target cells (e.g., tumor or infected cells) and flag them for destruction by immune effector cells.

Clinical Applications
Cancer: Used in hematological malignancies, often following stem cell transplantation to prevent relapse.
Autoimmune Disease:
Investigated for refractory rheumatoid arthritis, myositis, and other B-cell-mediated disorders.

Combination Therapies
Often paired with monoclonal antibodies (mAbs) or CAR-engineering to improve targeting, persistence, and efficacy.
This approach aims to provide a more accessible and cost-effective alternative to CAR-T therapies.

"Off-the-Shelf" Potential
Unlike CAR-T, NK cells from donors (especially umbilical cord blood) generally do not cause graft-versus-host disease (GvHD), making them faster and more accessible.

Solid Tumor Target
While initially for blood cancers (leukemia, lymphoma), CAR-NK is being tested for solid tumors like breast, ovarian, pancreatic, and glioblastoma.

Clinical Status and Considerations
Experimental Status: While showing promise, many NK cell therapies are still in clinical trials.

Reduced Side Effects: Compared to other immunotherapies, NK cell therapies often present fewer severe side effects.

Monitoring Activity: NK cell function can be measured (NK Cell Activity test) to assess immune strength and risk of infection or disease.

NK Cell Therapy Types
Autologous: Patient’s own NK cells are removed, activated, and returned.
Allogeneic: Donor-derived NK cells (including from cord blood or stem cells), allowing for immediate treatment.
CAR-NK: Engineered with synthetic receptors for enhanced targeting.

11/01/2026

My patient with left shoulder pain (frozen shoulder) combined with shoulder subluxation

A 63 old female stroke patient with left hemiparesis and left shoulder pain (frozen shoulder) combined with shoulder subluxation with downward displacement who comes to take rehabilitation treatment to my clinic after 1½ years of stroke attack.

Stroke rehabilitation timeline:
The most significant functional gains occurring in the first 3–6 months post-stroke. While recovery speeds slow after 6 months, improvement often continues for 18 months or more.
But this patient has not gotten improvement until 18 months after stroke attack.
The combination of stiffening (capsulitis) and shifting (subluxation) may significantly limit upper limb rehabilitation.

Capsulitis (frozen shoulder) combined with shoulder subluxation is a common, painful, post-stroke complication occurring in 17-81% of patients, usually within 3 weeks to 3 months.
It causes severe pain, stiffness, and reduced range of motion due to weak muscles, gravity-induced stretching of the joint capsule, and inflammation.

Subluxation occurs in the first 3 weeks due to flaccid muscle tone. About 67% of cases can worsen over time,
Hemiplegic shoulder pain often presents within 2-3 months post-stroke. While some experience relief in 1–6 months, up to 76.7% may experience pain for longer than 6 months.

Normally this patient could not get further progress but the shoulder pain can be relieved by intracular injection of corticosteroid and vitamin B12 injections near the nerve on brachial plexus and radial ulnar and medial sites of arm on affected side, followed by daily physical exercise.
Subluxation and weakness of muscles on left side can improve slowly and the patient can get gradual improvements through dedicated, ongoing therapy by using multiple vitamin B12 injections near the nerve at limbs and body sites on affected side followed by daily physical exercises.

10/01/2026

Dendritic cell (DC) Therapy (Therapeutic Vaccine)

Dendritic cells (DCs) are crucial immune sentinels that bridge innate and adaptive immunity, acting as master regulators by capturing, processing, and presenting foreign antigens (like from pathogens or cancer) to T cells in lymph nodes to initiate specific immune responses, while also maintaining tolerance to self-antigens, thanks to their branched, tree-like ("dendritic") structures that help them sense the environment.

Dendritic Cell (DC) therapy is a personalized, advanced immunotherapy that trains a patient's own immune cells to identify and attack cancer. By extracting dendritic cells, "educating" them in a lab with tumor antigens, and reintroducing them, the therapy triggers a targeted T-cell response to eliminate cancer cells while minimizing side effects compared to traditional treatments.
DC therapy is a personalized treatment, often termed a "therapeutic vaccine," used to treat existing cancers.

Process
Dendritic cells, the most potent antigen-presenting cells (APCs), are isolated from the patient's blood or bone marrow.
These cells are "loaded" in a lab with specific tumor proteins (antigens) from the patient's own cancer. These cells are matured and "trained" to recognize specific cancer antigens (proteins) from the patient's tumor.
They are then injected back into the patient (often into the skin).

Immune Activation
These activated DCs migrate to the lymph nodes, the immune system's command centers.
In the lymph nodes, these DCs present the cancer antigens to naive T-cells via MHC molecules (Major Histocompatibility Complex), activating them to find and destroy cancer cells throughout the body.

This process also creates immunological memory, allowing the immune system to mount a quicker response if the cancer reappears.

Cancer Types
Used for various solid and hematological tumors, (melanoma, prostate, lung, breast,) including promising results for glioblastoma.

Efficacy & Safety
Generally well-tolerated, with side effects often limited to mild, temporary immune-related inflammation.
2025 data suggests up to 88% one-year survival in certain patient groups.

Challenges
High production costs and the immunosuppressive tumor microenvironment can limit effectiveness.

Current Developments:
mRNA Technology
DCs are increasingly being loaded with in vitro transcribed mRNA to improve efficacy and simplify preparation.

Combination Therapies
Research focuses on combining DC vaccines with immune checkpoint inhibitors (ICIs) to boost anti-tumor immunity.

Off-the-shelf Options
Next-generation, "off-the-shelf" vaccines like vididencel are in development, aiming to simplify treatment.

02/01/2026

T cell egress technolog (S1PR1 Expression in T Cells)
T cell egress technology manipulates the exit of T cells from lymph nodes (LNs) and tissues into the bloodstream, primarily by targeting the sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) pathway.
Drugs like FTY720 (fingolimod) block this pathway to trap autoimmune T cells in LNs. Conversely, manipulating (S1PR1) or CCR7 can modulate the trafficking of CAR T-cells and tumor-infiltrating lymphocytes (TILs) for improved immunotherapy.

T cell egress is the highly regulated process by which mature T cells exit lymphoid organs (like lymph nodes) into the blood, driven primarily by the S1P1 receptor (S1PR1) gradient. S1PR1 on T cells binds to high concentrations of sphingosine-1-phosphate (S1P) in the lymph/blood compared to low levels in the lymph node, triggering migration out.

Sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) pathway is a critical G protein-coupled receptor (GPCR) signaling mechanism that regulates immune cell trafficking (lymphocyte egress from lymphoid organs), vascular development, and endothelial barrier integrity.
T cell expression of (S1PR1) enables them to follow an S1P gradient out of lymph nodes.

Spinster homolog 2 (SPNS2)
a specialized transmembrane protein acting as the primary exporter of sphingosine-1-phosphate (S1P) from cells into the blood and lymph. It regulates immune cell trafficking, vascular development, and, when inhibited, can modulate cancer metastasis and autoimmune diseases.
Role of SPNS2: The transporter SPNS2 is crucial, as it supplies S1P to the lymph, enabling the exit.

CCR7-CCL21 Axis: CCR7 acts as a "tissue exit receptor" that promotes the movement of effector T cells from inflamed sites into the lymphatics.
CXCR4/CXCL12 Inhibition: In tumors, the CXCL12/CXCR4 axis can limit T cell egress, allowing them to remain and fight cancer. Disrupting this axis can influence the retention vs. exit of CAR T-cells.

Clinical Applications
Autoimmune Diseases: Trapping autoreactive T cells in lymph nodes using (S1PR1) modulators (e.g., multiple sclerosis treatment).
Cancer Immunotherapy (CAR T/TILs): Enhancing the retention of effector T cells within tumor tissues to improve tumor control.
Transplant Rejection: Controlling T cell migration to reduce the immune response against transplanted organs.

Current Research Directions
Targeting SPNS2: Developing inhibitors for the SPNS2 transporter for more precise control over S1P signaling than broad (S1PR1) agonists.
Controlling Effector T Cell Trafficking: Investigating how to maintain high levels of tumor-specific T cells within tumors by inhibiting their premature egress.
Regulation of Memory T Cells: Understanding how Tissue-Resident Memory (T_RM) cells are kept in place, as opposed to recirculating T cells that use the S1P-dependent egress route.

01/01/2026

Viral mRNA Vaccines

mRNA vaccines represent a novel, fast-acting technology that uses genetic instructions to teach cells how to produce a protein that triggers an immune response against a virus.
Viral mrna vaccines technology use a synthetic, single-stranded mRNA sequence to instruct human cells to produce a viral protein, triggering a protective immune response.
They are fast to develop, highly effective against COVID-19, and are being researched for influenza, HIV, RSV, and Zika.

mRNA vaccines deliver a synthetic, transient mRNA sequence into cells, instructing them to produce a specific, harmless viral protein (e.g., the SARS-CoV-2 spike protein).
The immune system recognizes this protein as foreign and produces antibodies and T-cells, preparing the body to fight the actual virus if exposed.

Key Steps in the mRNA Vaccine Process:
Design and mRNA Synthesis: Scientists identify the genetic sequence for a viral surface protein and synthesize a corresponding mRNA strand in a lab.

Encapsulation: The mRNA is encapsulated in lipid nanoparticles (LNPs) to protect it and facilitate entry into human cells.

Vaccine Administration: The vaccine is injected into the body, and the LNPs deliver the mRNA into the cytoplasm of cells.
Protein Production: The cell's machinery (ribosomes) reads the mRNA and translates it into the viral protein.

Immune Response: The produced protein is displayed on the cell surface, triggering the immune system to produce antibodies and T-cells.

Memory Generation: The immune system remembers the pathogen, allowing for rapid, protective response if exposed to the actual virus in the future.

This technology is highly versatile, allowing for rapid development against new viruses, as it does not require growing the virus itself.
The platform is considered a potential future for preventing various infectious diseases, including those where traditional vaccines have not been successful.

New SARS-CoV-2 variants highlight the need for vaccines with improved potency and durability. This report presents a novel mRNA vaccine platform encoding virus-like particle antigens (mRNA-VLPs) that mimic native virus structures, aiming to boost antibody responses via enhanced B cell activation .

Picornaviral 3C and 3CD proteases are essential enzymes that process the viral polyprotein, primarily cleaving Gln-Gly bonds to mature viral proteins.
Due to their critical role in the viral life cycle, 3C/3CD are high-priority targets for the development of antiviral drugs, including both covalent and non-covalent inhibitors.
The 3C protein and/or the 3C domain in 3CD also have important RNA-binding capabilities.

Challenges:
The technology requires specialized, cold-chain storage and ongoing research into enhancing the stability and immunogenicity of the lipid nanoparticles (LNPs) used for delivery.

https://www.nature.com/articles/s41541-025-01303-w

https://www.mdpi.com/1999-4915/17/11/1473

https://scitechdaily.com/this-viral-rna-structure-could-lead-to-a-universal-antiviral-drug/

The COVID-19 pandemic spurred mRNA vaccine innovation, but new SARS-CoV-2 variants highlight the need for vaccines with improved potency and durability. This report presents a novel mRNA vaccine platform encoding virus-like particle antigens (mRNA-VLPs) that mimic native virus structures, aiming to....

27/12/2025

Allogeneic "Off-The-Shelf" CAR T-Cell Therapies

Allogeneic "off-the-shelf" CAR T-cell therapies are pre-manufactured from healthy donor cells, offering immediate availability for cancer treatment without the manufacturing delays or patient-T-cell limitations of traditional autologous therapies.
These "universal" products are engineered (e.g., using CRISPR) to reduce graft-versus-host disease (GvHD) and reduce MHC class I/II expression to minimize host-mediated rejection, providing a scalable,, standardized, and potentially lower-cost alternative.

Key Engineering Strategies & Technologies
Graft-versus-host disease (GvHD) Mitigation (TCR Disruption):
To stop the donor cells from attacking the patient, the T-cell receptor alpha constant (TRAC) gene is knocked out.
To prevent host immune cells from destroying the therapy, beta-2 microglobulin (B2M) is knocked out to eliminate HLA class I molecules.
Expression of cytokines like IL-15 is used to improve the in vivo survival of these cells.

Common Sources: Cells are often sourced from healthy donor peripheral blood mononuclear cells (PBMCs), umbilical cord blood, or induced pluripotent stem cells (iPSCs).

Key Aspects of Allogeneic Off-the-Shelf CAR T-Cells
Ready-to-Use: Unlike personalized, patient-derived cells, these are cryopreserved and ready for, immediate, "on-demand" patient use.
Overcoming Limitations: They address issues in cases where a patient’s own T-cells are too weak or damaged from prior treatments, and they prevent manufacturing failures.

Applications:
These therapies are being tested for cancer (e.g., B-cell malignancies) and for treating infections, such as using virus-specific T-cells (VSTs) for refractory viral infections.

Current advancements include "smart" CAR T-cells designed to turn on only within the tumor microenvironment (using logic gates) to improve safety and efficacy against solid tumors.

22/12/2025

Recent my patient

A 40 years old male strok patient with right hemiparesis and facial palsy came to take rehabilitation treatment on yesterday.
The patient has gotten stroke attack since last one month ago and hospitalized in 1000 brded hospital and took treatments.
On history he has hypertension, smoking, drinking and betel and to***co chewing habits.
CT head scan demonstrates left intracerebral hematoma at putamen which extends into the internal capsule and compress the left lateral ventricle.

The patient is presenting with left sided hemiparesis with left facial palsy but no choking and no dysarthtia. He can walk by aiding one person or with walking-stick and raise right hand upto chest.

The putamen is the most common site for hypertensive hemorrhages, which frequently extend into the internal capsule and compress the lateral ventricle.
Large putaminal hemorrhages have high mortality rates (44% within one month). Outcomes are dependent on the size of the hematoma, level of consciousness, and presence of significant brain shift (midline shift > 3 mm).

The patient may recover within 6 months after rehabitation tratment by using multiple vitamin B12 injections near the nerve on limbs and body sites on affected side followed by daily physical exercise.

Disclaimer: This information is for educational purposes only and does not constitute medical advice. A hemorrhagic stroke is a life-threatening emergency requiring immediate emergency medical care.

14/12/2025

CAR T-cell therapy for Rheumatoid Arthritis (RA)

BCMA (B-cell Maturation Antigen) is a receptor on B cells, crucial for their survival, and its pathway (with BAFF/APRIL) is overactive in rheumatoid arthritis (RA), promoting autoreactive B cells that produce damaging autoantibodies in joints, making BCMA a target for therapies like CAR T-cells, which show promise in eliminating these pathogenic B cells for drug-free remission in RA patients.

CD19 and CD20 are crucial cell surface proteins (antigens) found on B-cells, serving as markers for B-cell development,
CD19 is present from early B-cell stages through plasma cells, while CD20 appears later and is lost in mature plasma cells.
CAR T-cell therapy targeting CD19 (and sometimes CD20) shows significant promise for treatment-resistant Rheumatoid Arthritis (RA).
CD19-targeted CAR T-cells to deplete CD19-positive B-cells and plasmablasts, which are key producers of autoantibodies (like Rheumatoid Factor and ACPA) in RA.

BCMA and CD19 are complementary targets for CAR T-cell therapy, creating a powerful combination to tackle blood cancers and autoimmune conditions more effectively than single-target therapies.
It hits B-cells at different maturation stages (CD19 on early/mature B-cells, BCMA on plasma cells).

This deep B-cell depletion can effectively stop autoantibody production and potentially "reset" the autoimmune response, leading to long-term remission.
Achieves deep B-cell depletion, sometimes more effectively than traditional therapies like rituximab, which targets CD20.

Case studies show patients achieving drug-free remission with normalized inflammatory markers and significant drops in autoantibody levels.
It appears highly effective in severe, treatment-resistant RA (polyrefractory) and other autoimmune diseases like lupus.
It may also target autoreactive T-cells or other inflammatory cells involved in joint damage.

Challenges
Toxicity: Severe side effects like Cytokine Release Syndrome (CRS) and ICANS (neurotoxicity) have been observed, requiring intensive management.

Accessibility: High cost and manufacturing complexity remain significant hurdles for widespread use.

It's considered a potential later-line option for severe cases, not a replacement for standard RA treatments.
Long-term durability is still being studied, as CAR T-cells can become exhausted.

CAR T-cell therapy offers a powerful, "curative" potential for recalcitrant RA by deeply clearing the cells responsible for the disease, but it's an intensive, specialized treatment still under significant development.

Researchers are developing CAAR T cells (Chimeric Autoantibody Receptor T cells), derived from CAR T-cell technology, designed to treat autoimmune diseases by precisely targeting and eliminating the specific B cells that produce harmful autoantibodies, rather than indiscriminately suppressing the immune system

https://rdcu.be/eQHG2

06/12/2025

အိုမင်းခြင်းကိုမဖြစ်အောင် မိုက်တိုခွန်ဒရီးယားကောင်းမွန်သည့်အခြေအနေအပေါ်ပစ်မှတ်ထားသည် စီမံချက်မဟာဗျူဟာများ
၁၊ ကောင်းမွန်သော မိုတိုခွန်ဒရီးယားအသစ်များဖြစ်ပေါ်အောင်လှုံဆော်ခြင်း (biogenesis)
၂၊ ပျက်စီးသွားသည်မိုက်တိုခွန်ဒရီးများကိုရှင်းလင်းခြင်း (mitophagy)
၃၊ အင်တီအောက်စီဒင့်ကုထုံး (antioxident therapy)
၄၊ မိုက်တိုခွန်ဒရီးယားအစားထိုးခြင်း
(mitochondrial transplantation)
၅၊ ပြင်းအာနည်းလေဆာ သို့မဟုတ် အနီအောက်ရောင်ခြည် (low level laser or) infra red) တိုကို အသုံးပြုကုသပေးခြင်း (Photobiomodulation)
၆၊ မိုက်တိုခွန်ဒရီးယားသို့ ဆေးဝါးပို့ဆောင်ပေးခြင်း (drug delivery)
၇၊ လူနေမှုပုံစံ နှင့် အစားအသောက် (life style diets) တို့ဖြစ်သည်

Ant-aging Strategies Focus On Targeting Mitochondrial Health

Mitochondrial dysfunction is a core hallmark of aging, creating a vicious cycle where declining mitochondrial efficiency leads to increased cellular damage, energy deficits, and oxidative stress, accelerating the aging process and contributing to age-related diseases like neurodegeneration, metabolic syndrome, and cardiovascular issues.

This dysfunction involves decreased ATP production, elevated Reactive Oxygen Species (ROS), mitochondrial DNA mutations, impaired mitophagy (quality control), and disrupted calcium balance, ultimately causing systemic deterioration and increased disease risk.

Mitochondrial Dynamics: Imbalances in fission (splitting) and fusion (joining) affect mitochondrial size, number, and function.

DNA Damage: Accumulation of mutations and deletions in mitochondrial DNA (mtDNA) compromises function.

Vicious Cycle of Aging
Initial Damage: Aging stressors (like ROS) damage mitochondria.
Reduced Function: Damaged mitochondria produce less energy and more ROS.
Worsened Damage: Increased ROS causes more mtDNA/protein damage.
Systemic Decline: Cellular dysfunction spreads, impacting tissues and organs,
leading to age-related pathologies.

Associated Age-Related Conditions
Neurodegenerative diseases (e.g., Alzheimer's, Parkinson's)
Metabolic syndrome and Type 2 Diabetes
Cardiovascular diseases (e.g., atherosclerosis, hypertension)
Cancer
Sarcopenia (age-related muscle loss)

Key targeting mitochondria health
strategies include promoting
mitochondrial biogenesis,
removing damaged mitochondria through mitophagy, and
developing specific molecules to improve function or deliver antioxidants directly to the mitochondria.

Promoting : Strategies aim to stimulate the creation of new, healthy mitochondria.

Enhancing : Therapies can encourage the removal of damaged mitochondria, a process called mitophagy.

therapies: Molecules can be designed to target the mitochondria to combat oxidative stress. Examples include compounds conjugated with lipophilic cations.

: This is a novel approach being explored for certain conditions, such as bone diseases.

: This is another emerging strategy, particularly investigated for bone and cartilage health.

delivery: Researchers are creating novel methods, including using liposomes and other delivery systems, to deliver therapeutic agents specifically to the mitochondria.

Lifestyle and diet
Exercise: Aerobic exercise can increase mitochondrial density and improve their function.
Dietary Interventions: Diets like the ketogenic diet may support mitochondrial health.
Supplementation: Certain supplements such as CoQ10, B vitamins, and omega-3 fatty acids may support mitochondrial function.

Important considerations
Mitochondrial dysfunction is linked to a wide range of diseases, making targeting mitochondria a promising therapeutic avenue for many conditions.
Research is ongoing to understand and develop these strategies, with many molecules in development and clinical trials.

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