Dear Editor,
We read the article entitled “Nicotinamide Adenine Dinucleotide, the Sirtuins, and
the Secret of a Long Health Span” on the esteemed “Ibnosina Journal of Medicine and
Biomedical Sciences” with great interest. Anaizi reviewed the sirtuins, which is a
family of proteins with broad enzymatic activities.[[1]] Modifications in sirtuin activities have been associated with most age-related
pathologies including Alzheimer's disease (AD) and cardiovascular disease. Therefore,
its study could provide new pathological pathways and new therapies improving the
quality of life of individuals with cognitive decline.
AD is the most common type of dementia and may affect more than half of the population.
In addition, it is among the most frequent causes of death because contributes to
an increased risk of infection. AD is considered a neurodegenerative disease and it
interferes in the spheres of cognitive functioning such as memory, attention, executive
functioning, and language. The onset of AD typically is associated with age and normally
presents with short-term memory loss and executive functioning. Functional and structural
neuroimaging in AD are promising techniques to supplement the diagnosis and monitor
the clinical course of the disease.[[2]] The management of AD to date is only symptomatic including cholinesterase inhibitors
and Partial N-Methyl D-Aspartate antagonists. In this context, donepezil (Aricept)
was approved in 1996 and memantine in 2003 by the Food and Drug Administration.[[3]] Here, our objective is to provide a comprehensible overview of two new drugs for
AD. These medications are important because they have new promising mechanisms and
are derived from different substances.
In China, an algae-derived drug called GV-971 (Oligomannate) indicated for mild to
moderate AD was approved in November 2019. It is extracted from an oligosaccharide
marine alga and is the first novel drug approved for this disorder globally since
2003.[[4]] The mechanism of the drug is in the microbiome found in the gastrointestinal tract.
It is believed that a disbalance in the microbiota causes a misleading peripheral
and central inflammatory process causing increase amyloid protein deposits and tau
hyperphosphorylation. Hence, the algae-derived inhibits or decreases the development
of this pathological pathway. GV-971's III trial was done in a multicenter, randomized,
double-blind, placebo-controlled, parallel-group, for almost a year, and more than
800 subjects with diagnosed mild-moderate AD were included. The results were promising
and maintained throughout the study with a difference in the AD Assessment Scale-cognitive
subscale of 2.54 (P < 0.0001) between the active drug group and placebo. However,
some important facts to be highlight are that the study was only made in the Chinese
population so studies in other populations are warranted. Moreover, the effect of
the GV-971 is probably not equal for everyone because when the microbiome of the gut
is analyzed there is a wide variation among individuals even in the same family.[[5]],[[6]]
Aducanumab is another drug under study, which is a recombinant human monoclonal antibody
IgG1 κ targeting β-amyloid (Aβ). It is derived from the previously identified library
of B cells collected from healthy elderly individuals with and without signs of cognitive
impairment. The assumed mechanism of action of this drug is the targeting aggregated
forms of Aβ, including soluble oligomers and insoluble fibrils deposited into the
amyloid plaque in the brain of AD patients. In animal models, aducanumab entered the
brain, bind parenchymal Aβ, and reduce soluble and insoluble Aβ in a dose-dependent
manner.[[7]] Aducanumab did not lead to the required results, but after further analysis with
higher doses, resulting in a significant reduction in the cognitive symptoms. More
studies about aducanumab are therefore warranted and clinical trials are needed.[[8]],[[9]]
Authors' contributions
Equal.
Compliance with ethical principles
Ethical Approval not required
Reviewers:
Not Applicable (Correspondence)
Editors:
Salem A Beshyah (Abu Dhabi, UAE)
