Stem Cell Therapy for Alzheimer's | Regenerative Neurology

Alzheimer’s is a complex neurological disease that affects multiple neurons in parts of the brain. The exact mechanism is yet unknown. Extended studies have reported dysfunction in ‘amyloid beta’ and ‘tau’ proteins affecting distinct brain areas. It is the most common cause of dementia and accounts for 60-80% of dementia cases.

Alzheimer’s does not account for the normal part of aging. However, the majority of the cases presented are among individuals above 65 years. Younger-onset or early-onset Alzheimer’s are reported among individuals at 40-50 or 60 years.

Currently, there is no cure for Alzheimer’s. The current treatment offers limited long-term improvement. With growth research, scientists are emphasizing Stem Cell Therapy for Alzheimer’s as a regenerative option.

Ask The Expert

What Happens Inside the Brain in Alzheimer’s?

The pathological features in Alzheimer’s lie in multifactorial brain dysfunction. Alzheimer’s Disease Causes include:

Amyloid-Beta Plaque Accumulation: It leads to cognitive decline. The misfolding of the amyloid-beta protein leads to the accumulation or formation of beta-sheets between the neurons. This leads to neuronal toxicity and disruption of normal cellular function.
Tau Protein Tangles: Forms insoluble protein filaments. Tau protein gets abnormally hyperphosphorylated, leading to the breakdown of microtubules and the degeneration of brain cells.
Neuroinflammation: Microglia and astrocytes become hyperactivated, triggered by amyloid-beta dysfunction. Their activation stimulates the release of pro-inflammatory markers, resulting in neuroinflammation.
Oxidative stress: Excess production of free radicals (reactive oxygen species) triggers inflammatory signals. Oxidative stress promotes the accumulation of amyloid beta and tau protein, leading to mitochondrial damage and neuronal loss.
Genetic Factor: Early onset triggered by mutation of genes like APP, PSEN1, PSEN2, etc. Late onset triggered by APOR ε4 allele

Clinical Overview: Symptoms and Treatment

Alzheimer’s Symptoms Include:

Memory loss or confusion
Difficulty in reasoning abilities or making plans
Language and communication difficulties
Change in mood and personality
Declined ability to make decisions and
Compromised ability to perform daily life activities

Alzheimer’s Disease Treatment includes:

There is no cure for Alzheimer’s. The current conventional Alzheimer’s disease treatment aims to manage the symptoms. Common options include:

Cholinesterase Inhibitors: Block enzymes that speed up Alzheimer’s progression. E.g: Donepezil, Rivastigmine, Galantamine
NMDA Receptor Antagonists: Bind with excessive glutamate in the brain, slowing down the disease progression. E.g: Memantine
Intravenous Infusion: Trigger the immune system to target and neutralize amyloid proteins. E.g: Lecanemab, Donanemab
Management of Co-Morbid Factors: antidepressants (anxiety, depression, mood swings), antipsychotics (hallucination, paranoia, agitation), antiseizure (mood swings)
Cognitive Rehabilitation: Cognitive stimulation therapy is designed to be individual-specific. Supports memory improvement and problem-solving skills
Supportive Therapies: Occupational therapy for assisting the patient in performing daily life activities

*NOTE: All the above therapies induce short-term solutions and aid in symptom management. The patient with Alzheimer’s needs to follow the treatment regimen strictly for their lifetime. This marks the need for a new treatment regimen.

How Regenerative Medicine Is Transforming Neurology?

Regenerative medicine is transforming the therapeutic landscape in neurological research, including Alzheimer’s. Using stem cells for repairing neurodegenerative damage and regeneration of neural cells is widely explored.

Stem Cell Therapy for Alzheimer’s focuses on neurorestoration. Researchers focus on a regenerative approach that protects existing neurons. They improve synaptic communications, and boost cellular recovery within the brain. It aids in functional recovery. Currently, the regenerative medicine field is still investigative, and neurorestorative research presents a promising direction in natural healing of the brain’s functions.

Stem Cell Therapy for Alzheimer’s Disease

Researchers have widely expected the use of mesenchymal stem cells (MSCs) for Alzheimer’s Disease Treatment. The key mechanisms involved in natural brain function repair include:

Neural Regeneration: MSCs release various growth factors and cytokines that enable the regeneration of new neural cells. It supports neurogenesis
Neuroprotection: MSCs release various neurotrophic factors that protect the existing neurons in the brain
Improve Cognitive Function: Stem cells boost brain cellular signalling and synaptic communication, and improve cognitive function.
Neuroinflammation: MSCs release various anti-inflammatory cytokines such as IL-4, IL-10, IL-13, TGF-β, etc. These molecules mitigate the effect of pro-inflammatory cytokines and reduce neural inflammation.
Supports Angiogenesis: Supports an adequate supply of oxygen and nutrient delivery to neural tissue. Supports appropriate neural functioning
Supportive Microenvironment: MSCs create a supportive microenvironment that protects the brain microenvironment and supports neuronal cells [1]

Stem Cells Being Investigated in Alzheimer’s Research

Mesenchymal Stem Cells (MSCs): Immunomodulatory and anti-inflammatory properties. Cells are mainly isolated from the umbilical cord blood/tissues.
Neural Stem Cells (NSCs): Induce function in neuronal replacement
Induced Pluripotent Stem Cells (iPSCs): Development of personalized regenerative approaches

Latest Advances in Clinical Study

Preclinical and clinical trials demonstrate the safety and tolerance of MSCs in Alzheimer’s patients. Stem Cell Treatment for Alzheimer’s in clinical trials has shown the following outcomes:

MSCs release paracrine molecules and macrovesicle’s in the bloodstream. These molecules reach the injury sites.
Improvement in cognitive function and brain health
Reduces swelling and repairs neural damage
Modulates immune health and reduces inflammation via the downregulation of pro-inflammatory factors
Clinical trials have shown safety and tolerance of MSCs in Alzheimer’s patients [2]

*NOTE: Currently, stem cell therapy for Alzheimer’s is at an early stage. In the future, large-scale clinical trials are needed to establish the long-term efficacy and safety of the therapy.

What are the Possible Scientific Challenges?

An individual’s dependent response to stem cell therapy
Different cell sources lead to variability in isolated cell features.
MSCs’ isolation, proliferation and integration are a complex process; the challenge remains in stem cell survival.
Use of superior-quality stem cells is crucial in delivering effective results.

*NOTE: Advancells, India, is a leading stem cell research laboratory that isolates and manufactures superior quality stem cells for various neurological disorders.

Who Can Consider Stem Cell Treatment?

Individuals at the early to moderate stage of Alzheimer’s development
Decision based on patients’ detailed health evaluation report, consideration of co-morbid health factors (metabolic disorder, hypertension, hyperlipidemia, other health issues)
Individuals seeking supportive treatment options
An individual in stable condition should not have any active infection or cancer.

Future Directions in Alzheimer’s Disease Treatment

Regenerative medicine for improving cognitive decline and regulating brain function
Biomarker-guided precision therapy development
Combination therapy using stem cell therapy with conventional treatment
Development of personalized neurodegenerative medicine

Conclusion

Stem Cell Treatment for Alzheimer’s is promising as a curative option. It can potentially deliver a natural repair mechanism in the brain. Though the treatment is at an early stage, preclinical and clinical studies have marked the safety of the treatment. The combination of stem cell therapy with conventional medication is a potential means of targeting beta-amyloid and reducing amyloid deposits.

Alzheimer’s Disease Patient Success Stories

References

Liu Y, Liu Y, Zhang R, Huang J. The therapeutic efficacy of mesenchymal stem cells for Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2019;68(1):111-126.
Hernández AE, García E. Mesenchymal stem cell therapy for Alzheimer’s disease. Stem Cells International. 2021;2021(1):7834421.

FAQ’s

Q- Can Stem Cell Therapy Lead to Neurorestoration in Alzheimer’s Disease?

Mesenchymal stem cells have reflected the potential in restoring neural function. They improve neuronal connectivity, support neural cell regeneration, and promote repair mechanisms. It aids in neurorestoration at damaged sites.

Q- What is the Role of MSCs in Alzheimer’s?

MSCs display paracrine effects at the damaged brain site. The cells combat neuroinflammation, modulate immune response, promote synaptic communication, and create supportive microenvironments.

Q- Can Stem Cell Therapy be Considered as a Curative Option for Alzheimer’s?

Currently, stem cell therapy is at an early stage of therapeutic application. Currently, it has displayed safety and tolerance among patients. It has potentially been displayed as supportive therapy. In the future, large-scale clinical trials are needed to establish the long-term safety and efficacy of the therapy.

Latest Advances in Stem Cell Therapy for Alzheimer’s Disease

Introduction