Alzheimer's disease treatment
Zhou et al. identified thonningianin A as a potent microglial autophagy enhancer in enthorum chinense Pursh (PCP) that promotes the autophagic degradation of the NLRP3 inflammasome to alleviate the pathology of Alzheimer's disease via the AMPK/ULK1 and Raf/MEK/ERK signaling pathways, which provides novel insights for TA in Alzheimer's disease treatment 1).
The main methods of non-invasive brain stimulation are repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Preliminary findings have suggested that both techniques can enhance performances on several cognitive functions impaired in Alzheimer Disease AD. Another non-invasive emerging neuromodulatory approach, the transcranial electromagnetic treatment, was found to reverse cognitive impairment in AD transgenic mice and even improves cognitive performance in normal mice. Experimental studies suggest that high-frequency electromagnetic fields may be critically important in AD prevention and treatment through their action at the mitochondrial level. Finally, the application of a widely known invasive technique, the deep brain stimulation (DBS), has increasingly been considered as a therapeutic option also for patients with AD; it has been demonstrated that DBS of fornix/hypothalamus and nucleus basalis of Meynert might improve or at least stabilize cognitive functioning in AD.
Initial encouraging results provide support for continuing to investigate non-invasive and invasive brain stimulation approaches as an adjuvant treatment for AD patients 2).
Literature on the pathophysiology of AD, including translational data and human studies, has been studied to generate a fundamental hypothesis regarding the effects of Electrostimulation on cognition and to facilitate a ongoing pilot study regarding DBS of the nucleus basalis of Meynert (NBM) in patients with AD.
It is hypothesized that DBS in the nucleus basalis Meynert could probably improve or at least stabilize memory and cognitive functioning in patients with AD by facilitating neural oscillations and by enhancing the synthesis of nerve growth factors.
Considering the large number of patients suffering from AD, there is a great need for novel and effective treatment methods. Hardenacke et al. research provides insights into the theoretical background of DBS in AD. Providing that the hypothesis will be validated by our ongoing pilot study, DBS could be an opportunity in the treatment of AD 3).
The precise mechanisms by which DBS may enhance memory and cognitive functions in Alzheimer's disease patients and the degree of its clinical efficacy continue to be examined in ongoing clinical trials 4).
Disease-modifying therapies
Disease-modifying therapies (DMTs) for Alzheimer's disease (AD) have early evidence of efficacy. Widespread delivery of DMTs will require major service reconfiguration. Treatment pathways will need to include triaging for eligibility, regular infusions and baseline and follow-up MRI scanning. A critical step in planning is provision of real-world estimates of patients likely to be eligible for triaging, but these are challenging to obtain.
Disease-modifying therapies (DMTs) for Alzheimer's disease aim to slow down the progression of the disease, address the underlying pathology, and improve or stabilize cognitive function. Alzheimer's disease is characterized by the accumulation of amyloid-beta plaques and tau tangles in the brain, leading to neuronal damage and cognitive decline. Here are some of the key disease-modifying therapies and investigational approaches for Alzheimer's disease:
Approved Therapies
1. Aducanumab (Aduhelm)
Mechanism of Action: Aducanumab is a monoclonal antibody that targets amyloid-beta plaques in the brain, promoting their clearance. Approval: Approved by the FDA in 2021 under the accelerated approval pathway. Efficacy: Clinical trials have shown that Aducanumab can reduce amyloid plaques, although its impact on cognitive function improvement remains a subject of debate. Controversy: Its approval has been controversial due to mixed results regarding its clinical benefits and high cost.
2. Lecanemab Mechanism of Action: Another anti-amyloid monoclonal antibody targeting amyloid-beta plaques. Development: Lecanemab has shown promising results in reducing amyloid plaques and slowing cognitive decline in early and mild Alzheimer's disease patients in clinical trials.
Investigational Therapies
1. Anti-Tau Therapies Mechanism of Action: These therapies aim to prevent the formation or promote the clearance of tau tangles, which are another hallmark of Alzheimer's pathology. Examples: Antisense oligonucleotides (ASOs) and monoclonal antibodies targeting tau proteins are under investigation. Status: Several anti-tau therapies are in various stages of clinical trials.
2. BACE Inhibitors Mechanism of Action: Beta-secretase (BACE) inhibitors reduce the production of amyloid-beta by inhibiting the enzyme BACE1, which is involved in the cleavage of amyloid precursor protein (APP). Examples: Verubecestat, Lanabecestat. Status: Despite initial promise, many BACE inhibitors have faced setbacks due to safety concerns and lack of efficacy in late-stage clinical trials.
3. Anti-Inflammatory Agents Mechanism of Action: These therapies aim to modulate the immune response and reduce neuroinflammation, which is thought to contribute to Alzheimer's pathology. Examples: Non-steroidal anti-inflammatory drugs (NSAIDs), microglia-targeting therapies. Status: Ongoing research is investigating various anti-inflammatory agents and their impact on Alzheimer's progression.
4. Neuroprotective Agents Mechanism of Action: These agents aim to protect neurons from the damage caused by amyloid-beta and tau pathology. Examples: Neurotrophic factors, antioxidants, and mitochondrial function enhancers. Status: Several neuroprotective agents are in preclinical and clinical development.
5. Immunotherapy Mechanism of Action: Active and passive immunotherapies aim to stimulate the immune system to target and clear amyloid-beta or tau aggregates. Examples: Vaccines against amyloid-beta or tau, monoclonal antibodies. Status: Various immunotherapy approaches are being tested in clinical trials with some promising early results.
Supportive Therapies In addition to DMTs, supportive therapies are essential to manage symptoms and improve the quality of life for Alzheimer's patients. These include:
Cholinesterase Inhibitors: Donepezil, rivastigmine, and galantamine help increase levels of acetylcholine in the brain, which can help with cognitive symptoms. NMDA Receptor Antagonists: Memantine helps regulate glutamate activity to prevent excitotoxicity and is used in moderate to severe Alzheimer's disease. Lifestyle and Behavioral Interventions: Cognitive training, physical exercise, and social engagement can support cognitive function and overall well-being.
Disease-modifying therapies for Alzheimer's disease represent a rapidly evolving field with several promising approaches under investigation. While current therapies like aducanumab and lecanemab offer some hope in slowing disease progression, ongoing research into anti-tau therapies, BACE inhibitors, anti-inflammatory agents, and neuroprotective strategies aims to provide more effective solutions. Combining these with supportive therapies can offer a comprehensive approach to managing Alzheimer's disease, aiming to improve the quality of life for patients and slow the progression of this debilitating condition.