Posted on 07 October 2022

​Dementia has been a more and more pressing issue in the public eye due to high profile cases of celebrities with the affliction such as Barbara Windsor, beloved for her part as Peggy in the soap Eastenders. In simple terms, Alzheimer's (the disease causing dementia) is; “a disease and brain disorder that slowly destroys memory and thinking skills and, eventually, the ability to carry out the simplest tasks”. Dementia has a wide scope in the functions it affects, although primarily it is memory, cognition and can even cause aggression and personality disorders in those in advanced stages of disease.

There are currently extremely limited treatment options for dementia and many of the drugs, such as memantine, which are only indicated for the slowing of the disease and are not regarded as a cure. Of course, there are a range of problems associated with dementia and it worsens frailty, causing falls and hip fractures. Instead of just affecting the individual, dementia can have extremely distressing effects to close family members, spouses and friends as the individual can change in their ability to communicate, remember, and carry out activities and the individual is not aware of these changes. Although care has been optimised to improve quality of life and halt the progression of the disease through lifestyle and other factors, a recent drug breakthrough could be the most promising therapeutic yet to be developed in the modern world.

Lecanemab, the drug in question, is the first drug developed which can powerfully improve symptoms and can bring the disease to a halt in its progression. The preliminary data came from a press release and was circulated widely online, claiming to be the best results from a clinical trial on the disease since drugs were beginning to be developed. Using an innovative antibody technique, Lecanemab binds to amyloid plaques in the brains of affected people, which is the primary culprit for disease progression due to build up and deposition. In targeting the plaque, the drug is directly tackling the causative factor in disease progression, rather than augmenting the function of other brain areas to compensate for failings in other parts of the brain. The specificity of this drug targeting amyloid plaque needs to be used directly in those affected by amyloid plaques, as there are a range of proteins which can cause the disease itself and thus this is a specific treatment for that protein.

Data from the phase 3 clinical trials did show side-effects, common in most drugs, when Lecanemab was used and there were risks of brain swelling and bleeding. The prevalence is low, and it is likely regulators will accept this risk to certify a drug in an area where the pharmacopoeia has failed to make significant gains. 3% of the participants experienced brain bleeds, and the data did not demonstrate the severity of those side effects. It’s likely the certification will be couched with an acceptance of that risk and clinical use will demonstrate the risk factors that influence the induction of these symptoms in certain populations. This does pose the problem that those suffering from other plaques and proteins like Lewy bodies are not suitable for this drug, and those individuals will be left still without effective treatment options. New blood tests will be developed to actively identify antigens or other products of plaque production to select the correct population for clinical use, yet a lot is riding on the development of these specific tests.

The data from the press release showed; “Lecanemab slowed the rate of cognitive decline in people with mild cognitive impairment and early-stage Alzheimer’s disease by 27% over 18 month”. This result is seen in other therpaeutics, but they only target the symptoms and not the causative factors. In real world terms, this could spell an extra 2 years of life expectancy for a dementia patient over a 6 year prognosis if they use Lecanemab for around a year and a half. The gamble comes with regulators like European Medicines Agency reviewing data after drug certification to see whether these gains outweigh the risk of brain bleeds and the other significant side effects. It’s not a silver bullet, but it is the first of a range of treatments which can show real world potential to improve quality of life, particular in those younger individuals who can be diagnosed as young as 50-60 years old. If certification happens, the individuals on the drug will likely be subject to myriad cranial MRIs to assess progress and scan for brain swelling, bleeding and other inflammation. Still, patients, regulators and families who assess these risks will likely see the significant secondary and tertiary effects to loved ones and the affected people and give clinicians the right to prescribe the drug to individuals who are looking for any way to get relief from the affliction.

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