Alzheimer’s disease is a form of dementia that predominantly occurs in older individuals (>65 years). It progressively diminishes cognitive skills and behavioral functions, including memory, speech, judgment, etc. The complex pathology of the disorder hinders the development of an effective cure. While the current modalities relieve symptoms, they have a moderate impact. Their administration as a combination augments the efficacy, but also increases adverse effects. Stem cell therapy for Alzheimer’s disease is a promising treatment option. It not only addresses the mechanisms of the disorder but also repairs neural damage to improve cognitive skills.
Alzheimer’s Disease Causes
Alzheimer’s disease occurs due to the loss of nerve cells (or neurons) in the brain. Based on clinical findings, two reasons have been hypothesized for causing this disorder:
- The levels of neurotransmitter- acetylcholine decline. It results in the eventual loss of neurons that utilize this neurotransmitter to relay signals across the brain. The buildup of beta-amyloid peptide also impairs the release of this neurotransmitter and disrupts the synaptic connection between two neurons.
- The widely accepted hypothesis, however, states that the primary cause is the accumulation of beta-amyloid. Beta- and gamma-secretase enzymes cleave amyloid precursor protein (APP) to generate non-toxic fragments. Beta-amyloid forms by the continual degradation of fragments by these enzymes. The deposition of this peptide also leads to hyperphosphorylation of the tau protein. The subsequent pathways result in misfolding of the tau protein and its aggregation in the form of helical filaments, named as neurofibrillary tau (NFT).
The Common Risk Factors Behind the Disease Include:
- Age: The risk of the disorder doubles every 5 years after the age of 65 years.
- Cardiovascular Disorders: These can lead to strokes in the brain, leading to neural loss.
- Diabetes: It promotes beta-amyloid accumulation and inflammation
- Obesity: It increases neuroinflammation, which exacerbates the disorder
- Genetic factors: Down syndrome is linked to Alzheimer’s disease. Mutations in three genes, AAP, PSEN1, and PSEN2, are also associated with this disorder. Additionally, the APOE allele and SORT1 are also correlated with the increased risk of the disease.
Several Other Factors Can Also Increase The Susceptibility to The Disease, Such As
- Traumatic head injury
- High parental age at birth
- Smoking
- Family history of the disorder
- Increase in homocystine levels
Alzheimer’s Disease Symptoms
The neural damage in the disease manifests as behavioral and cognitive deficits. The following symptoms indicate the initial stage of the disorder:
- Memory loss that interferes with day-to-day tasks
- Forgetting conversations
- Poor decision-making
- losing sight of the dates or the actual place
- Taking longer to finish routine chores
- Anxiety and confusion
As the disease progresses, patients tend to avoid social interaction and face difficulty in logical thinking, speech, writing, reading, etc. They start forgetting familiar places, past events, and relatives. It leads to restlessness, poor sleep, anxiety, and paranoia. With the worsening of the disorder, patients lose their communication ability and bladder/bowel control.
Alzheimer’s Disease Treatment
There is no cure for Alzheimer’s Disease. The existing treatment emphasizes managing symptoms and is classified into two categories:
Cholinesterase inhibitors: This class of drugs inhibits the enzyme (cholinesterase) that breaks down the neurotransmitter acetylcholine and includes rivastigmine, donepezil, and galantamine.
NMDA (N-methyl D-aspartate) antagonists: NMDA receptors inhibit the neurons that use acetylcholine. Antagonists of NMDA receptors, such as memantine, block this inhibitory pathway and, as a result, prevent neural loss.
These drugs have a limited effect. Their intake also leads to complications such as dizziness, body aches, constipation, headaches, etc.
New Alzheimer’s Treatments in 2025
Scientists are making persistent efforts to develop a better therapy for Alzheimer’s disease. In their pursuit, the following new treatments have emerged.
Disease-Modifying Therapies: These therapies employ monoclonal antibodies against beta-amyloid to change the course of the disease and slow its progression. Lecanemab (leqembi), donanemab, and aducanemab are few such drugs that are undergoing clinical trial. They have shown promising results. However, these therapies are associated with ARIA (Amyloid Related Imaging Abnormalities). ARIA is an immune response against these antibodies that compromise the blood vessels in the brain. The process consequently leads to blood leakage, resulting in swelling or clot formation that triggers neural loss.
Brain Shuttle: It exploits the transferrin receptor on brain cells of the blood-brain barrier. Transferrin transports iron across the barrier. Scientists are attempting to use the receptor to transport beta-amyloid antibodies through the barrier. The shuttle can reduce the dosage of antibodies and thus complications associated with them while retaining its efficacy. Trontinemab uses this mechanism, which has shown lower rates of ARIA and effective reduction of amyloid plaques.
Focused Ultrasound: It targets the ultrasound to one specific region in the brain, which temporarily opens the blood-brain barrier. The mechanisms behind its therapeutic effects in Alzheimer’s disease are not completely clear. But it is proposed that enhanced barrier permeability can activate brain microglia which can clear plaques by phagocytosis.
Drug Repurposing: Drugs that are already approved for other disorders can be repurposed for Alzheimer’s disease treatment. Semaglutide is a drug approved for type 2 diabetes treatment. It can traverse across the blood-brain barrier and exert neuroprotective effects, making it beneficial for the disorder. Similarly, irinotecan and letrozole are two cancer therapeutics that have demonstrated modified gene expression in neurons and reduced accumulation of beta-amyloid and tau.
Tau-Targeting Moieties: Tau deposition worsens the disease; therefore, scientists are formulating strategies that target biochemical processes of tau protein. For example tau expression (BIIB080), phosphorylation (sodium selenate, lithium chloride), acetylation (salsalate), glycosylation (ASN-51, LY3372689), and aggregation (LMTX), etc. Furthermore, antibodies against the tau protein are also under development.
Stem Cell Therapy for Alzheimer’s Disease
Treatment strategies that have been approved or are under evaluation are focused on one of the pathways of the disease, such as protein build-up or enzyme inhibition. To act on more than one pathway, a combination of one or more therapies is administered. However, they still fail to regenerate neurons for improved cognitive capacity. Stem Cell Therapy transcends such limitations by multifaceted effects that target the diverse pathologies of the disorder and also repair neural damage. The research has revealed that the stem cells can treat the disorder in the following ways:
- They reduce the size of amyloid-beta plaques
- These cells regulate the levels of APP and secretase enzymes
- They also induce neural progenitor differentiation into mature neurons by activating the Wnt signaling pathway. Moreover, stem cells can differentiate into neural cells to replenish the lost neurons
- Stem cells protect neural cells from toxic protein build-up, oxidative stress, and inflammation
- They also promote neural connectivity and improve blood supply
- These cells increase IL-10 levels that suppress neuroinflammation
- Stem cells activate microglial cells that can reduce plaques
These effects lead to improvement in cognitive skills and behaviors. Concomitant with research, clinical trials have begun on stem cell treatment. Laromestrocel- an allogeneic mesenchymal stem cell therapy- has shown encouraging results in phase 2 studies, showcasing the potential of the treatment.
Conclusion
Alzheimer’s disease is a complex disorder involving a multitude of biochemical processes. The mild impact of present treatments has fueled the search for effective alternatives. Several drugs are in the pipeline that target different aspects of the disorder. Even with modest improvements, these drugs fail to heal the damage that has occurred. Stem cell therapy works in a dual manner- acting on all the pathological mechanisms of the disorder and replenishing lost neurons. The potential of this treatment is under evaluation. The early studies have yielded favorable results. A large-scale clinical trial will soon translate the therapy into clinical settings. Advancells, a stem cell manufacturer, understands the potential of this therapy and delivers premium-quality Stem Cells for Alzheimer’s Disease Treatment. Its compliance to the legal and ethical standards demonstrates its dedication. Its scientific team ensures the quality of the product to maximize the benefits of the treatment.
FAQ’s
Q- Why does Alzheimer’s disease occur?
It occurs due to the accumulation of beta-amyloid, which results in neural loss.
Q- Is memory loss the only symptom of Alzheimer’s disease?
No, memory loss is the predominant symptom, but gradually the disorder causes difficulty in speech, swallowing, reading, writing, along with seizures, anxiety, and loss of bladder and bowel control.
Q- How does stem cell therapy treat Alzheimer’s disease?
The therapy reduces inflammation, regenerates neurons, and alleviates protein aggregation to improve cognitive skills in the patients.
Q- Is stem cell treatment safe?
Large-scale clinical trials are assessing the safety of stem cell therapy. However, early clinical trials have reported that stem cell therapy does not cause any complications.
Recent Comments