MSL and Alzheimer's Disease 

By Reena Khaira 

MSL professionals specializing in neurology are highly interested in Alzheimer’s disease (AD), a progressive brain disorder that often results in dementia, where concerted efforts with respect to both research and drug discovery have been made over the years. The underlying causes and fundamental mechanisms that lead to irreversible brain damage and cognitive decline are not fully understood thus proving difficult to determine an effective therapeutic target in symptomatic patients. AD affects approximately 50 million people worldwide, and is only becoming more prevalent in aging populations, so continued R&D into innovative and breakthrough treatments to address unmet medical needs in this disease area are essential to improve overall patient health outcomes and life expectancy.

Alzheimer’s disease is characterized by abnormal plaque buildup, astrogliosis, nerve cell atrophy, vascular damage, neurofibrillary tangles, and synaptic and neuronal loss. 1,2 Most AD research for the bulk of the past two decades has centered around amyloid peptides and tau proteins. The amyloid-β (Aβ) hypothesis states that accumulation of Aβ plaques in regions of the brain leads to the pathogenesis of AD as a result of Aβ clearance mechanism failures.2,3 The tau hypothesis, alternatively, suggests that phosphorylated tau proteins aggregate to form tangles (NFTs) that directly contribute to neurodegeneration.4 Additionally, candidate gene apoE4, located on chromosome 19, has been found in a number of genetic screens of AD that may indicate that it is a potential risk factor that plays a significant role in the development of onset AD and influences Aβ plaque buildup in the brain.5 And so, this poses the puzzling question: Is the aggregation of either Aβ or tau causing AD, or are they involved in the protein cascade events that result from the upstream factor apoliprotein E (apoE4) gene? 

MSLs operating in this therapeutic discipline must possess extensive scientific and clinical acumen, which entails staying abreast of the latest developments in the field and all current literature. Given the many mysteries and complexities surrounding AD, the expertise provided by MSLs is imperative when engaging with KOLs and HCPs because this dialogue ultimately influences how patients are being treated.  

As steady progress is made to garner a better understanding of AD diagnostic pathways, most available therapies in the pharmaceutical market aim to improve mental ability and function. The two common classifications of drugs include cholinesterase inhibitors and glutamate regulators. The latest clinical drug to be granted approval by the FDA is Aduhelm (aducanumab) made by the company Biogen, and is currently set at a market price of a whopping $56,000. This drug has been considered a landmark drug because, not only is it the newest Alzheimer drug to enter the market in 18 years, but it is also the first pathology-targeted treatment that works to reduce Aβ buildup. However, the accelerated approval of Aduhelm has stirred up some controversy. Many experts and scientists have raised concerns about the drug, noting that there is not sufficient evidence to support the claim that it slows cognitive decline. This has subsequently prompted an internal inquiry, while Biogen has been tasked to conduct another additional clinical trial. 

The implications of Aduhelm drug efficacy are yet to be seen, but we do know that new therapeutic solutions, whether they are small-molecule drugs, antibodies, or gene therapies, increase the demand for MSLs. The ever-changing landscape of medical intervention and studies compels healthcare systems to make greater investments in MSLs, who are uniquely positioned in their role to bridge the gap between industry and practice since they are involved with the drug life cycle every step of the way. As the product launch for Aduhelm rolls out in the near future, granted the clinical trial is successful in proving its claim, there is no doubt that MSLs will be instrumental figures in facilitating scientific exchange with the goal to promote human health and get this novel therapy prescribed to Alzheimer patients. 

References:

1. Hardy JA & Higgins GA. 1992. Alzheimer’s disease: the amyloid cascade hypothesis. Science 256:184-185.

2. Kametani F & Hasegawa M. 2018. Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's disease. Front Neuroscience 12: doi:10.3389/fnins.2018.00025. 

3. Selkoe DJ & Hardy J. 2016. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Molecular Medicine 8:595-608. 

4. Jesus R, de Paula V, Guimaraes FB, Diniz BS, Forlenza OV. 2009. Neurobiological pathways to Alzheimer’s disease: Amyloid-beta, TAU protein, or both? Dementia Neuropsychology 3:88-194.

5. Dodart JC, Marr RA, Koistinaho M, Gregersen BM, Malkani S, Verma IM, Paul SM. 2005. Gene delivery of human apolipoprotein E alters brain Abeta burden in a mouse model of Alzheimer's disease. Proceedings of the National Academy of Science USA 102:1211-6.