Release Date: 12-May-2023
Over the past couple of decades, immunotherapy has been a core part of the therapeutic landscape of cancer treatment. The introduction of immunotherapy in a complex disease like cancer has sparked the advancement of the method in several other complicated diseases. With continuous positive outcomes from immunotherapy, researchers are now to bringing this advancement to other complex diseases. A new addition to the therapeutic branch of immunotherapy has been towards neurodegenerative disorders like Alzheimer’s disease.
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Being a relatively growing health concern throughout the world with no disease modifying treatments, neurodegenerative disorders have been the subject to vast research. As a chronic neurodegenerative disorder, current therapeutic approach for Alzheimer’s disease include the use of cholinesterase inhibitors like Rivastigmine, Donepezil, Galantamine, and N- methyl- D- aspartate (NMDA) receptor antagonists. Although these methods have been able to generate positive outcomes to restrain the expression of symptoms like dementia for a period of time, they are unable to completely stop either the progression of Alzheimer’s disease or its symptoms.
Use of immunotherapy has become an increase important step in cancer treatment and now, its use has extended to neurodegenerative disorders. Several immunotherapies have been investigated in preclinical and clinical studies for Alzheimer’s disease targeting the production and aggregation of amyloid beta (Aandbeta;) in the brain. Playing a pivotal role in the pathogenesis of Alzheimer’s disease, amyloid beta causes synaptic impairment and neurodegeneration, therefore targeting Aandbeta; could possibly restrain the progression of Alzheimer’s disease.
For several years, agents targeting amyloid beta have been investigated in clinical trials and many have failed to produce desirable effects. With immunotherapy becoming the focus of exploration for neurodegenerative disease, targeting amyloid beta and promoting its clearance has become the priority, believed to be a promising disease modifying approach. Both active (use of vaccines) and passive (use of monoclonal antibodies) immunotherapies have been investigated in Alzheimer’s disease with the latter approach being developed much faster.
The incorporation of monoclonal antibodies in Alzheimer’s treatment has been a new approach; however, results from the clinical trials have presented promising results. Currently, there are two immunotherapeutic monoclonal antibodies which have been approved for their use in Alzheimer’s disease. Aducanumab is the first US FDA approved fully human IgG1 monoclonal antibody for the treatment of Alzheimer’s.
In June 2021, the US FDA approved the monoclonal drug product for the treatment of mild cognitive impairment or mild dementia stage of Alzheimer’s. Directed against the amyloid beta accumulates, the approval of Aducanumab presented a hallmark for the therapeutic landscape of Alzheimer’s disease. Approved under accelerated approval, it is the first therapy that targeted the fundamental pathophysiology of Alzheimer’s disease.
This monoclonal antibody was assessed in three separate clinical trials which consisted of double blind, randomized, placebo controlled, dose ranging studies. Patients which undergone the clinical trials had significant time and dose dependent reduction in amyloid beta plaque while patients in the control who did not receive Aducanumab had no effect on the accumulation of amyloid beta plaque. The results from this clinical study accelerated the approval process of Aducanumab.
Harnessing the body’s own immune response to prevent ore remove the accumulation of amyloid beta and Tau is believed to be a promising strategic approach for Alzheimer’s disease as Tau pathophysiology is associated with dementia symptoms. For decades, both active immunotherapy and passive immunotherapy methods have been tested in clinical and preclinical studies for neurodegenerative disorders like Alzheimer’s. Now, slowly as researchers understand the pathophysiology and key factors that lead to the progression of the diseases, immunotherapy is becoming a fundamental therapeutic approach.
Although there are some side effects present in the now approved immunotherapeutic monoclonal antibodies for Alzheimer’s disease, it cannot be denied that there introduction brought in a new light of treatment in an incurable disease like Alzheimer’s. With the possibility of slowing the neurodegeneration in Alzheimer’s disease and clearing amyloid beta aggregation, onset of Alzheimer’s immunotherapies can be expected to change the treatment landscape for other neurodegenerative diseases as well.