It is well known that Alzheimer’s disease is a devastating condition that is becoming a major concern to aging people. It may not be as feared as cancer but the numbers are not lying, we are steadily advancing towards a new epidemic with the potential to severely affect the healthcare systems of all countries. This fact has been recently highlighted by 2 reports concerning the latest estimates of worldwide prevalence{1} and the economic projections of treatments that delay onset of Alzheimer’s disease{2} in US.

According to these reports:

• 26.6 million people worldwide are living with Alzheimer’s and 5.1 of those live in the US.
• These numbers are expected to quadruple by 2050. It is estimated that more than 106 million people will suffer from Alzheimer’s worldwide 16 million of which will reside in the US.
• Assuming that treatments that could delay onset of the disease will be available by 2010 when the annual cost (Medicare only) is estimated to be $160 billion, it is estimated that by 2050 :
  • treatments delaying the onset of the disease by 1 year could save $1.2 trillion annually in US only, while at the same time they could reduce the number of patients by 12 million people, globally.
  • treatments delaying the onset of the disease by 2 years could reduce the number of patients by 18 million people globally.
  • treatments delaying the onset of the disease major symptoms by 5 years could save $4 trillion in US annually.

It is obvious that the combination of increasing costs and number of patients is already putting pressure to the pharmaceutical industry for real and effective treatment options for Alzheimer’s disease. In addition, healthcare systems like NICE seem unwilling to cover the prescription of expensive drugs that only treat symptoms. The time for innovation is here and is becoming imperative.

Are the scientific community and the pharmaceutical industry ready to provide with true solutions? Are they ready to offer treatment? It is generally believed that with advances made in research and drug development new disease modifying treatments should hit the market by 2010. Currently available drugs only treat symptoms. They protect the proper propagation of neuronal signals either with acetylcholinesterase inhibitors (Donepezil, Rivastigmine, Galantamine) or with NMDA receptor antagonists (Memantine). Both approaches, however, have nothing to do with the root of the disease. They simply improve for a short period of time the quality of life of affected individuals but the inevitable neurodegeneration is still active.

Which is the root of the disease? What causes Alzheimer’s disease? Definite answers to these questions are still pending. The widely adopted hypothesis suggests that aggregation of amyloid-beta peptides around neurons cause oxidative stress which in turn is responsible for the neurodegeneration and the cognitive problems that are characteristic in Alzheimer’s. Recently, an increasingly vocal portion of the scientific community claims that amyloid-beta accumulation is simply a pathologoanatomic hallmark of the disease and is preceded by oxidative stress and inflammation{3,4,5}. The latter two are believed to be the true pathogenic events for Alzheimer’s, a claim supported by many published results. It is interesting that:

• Cognitively intact aged individuals have been found with Amyloid-beta loads equivalent to patients with Alzheimer’s disease{6}.
• Amyloid-beta peptides, at low concentrations and before their accumulation into plaques act in a protective way against oxidative stress. However, when they form plaques, an event that is observed at later stages of Alzheimer’s disease they become toxic and induce oxidative stress{4}.
• A recent study has shown that even though currently available cholinesterase inhibitor drugs may reduce the amount of amyloid-beta they are still unable to offer substantial benefit in terms of treatment{7}.

Based on the above, one could assume that the recent trend of Pharma industry towards amyloid-beta lowering drugs (antibodies, vaccines, β- and γ- secretase inhibitors and other amyloid-beta reducing compounds) may not be the best approach. Moreover, there may be a chance that attacking amyloid-beta may do more harm than good since it may sequester a natural defensive mechanism against oxidative stress{8}.

A smarter approach would be to target the probable main cause of the disease, namely oxidative stress and inflammation, with ultimate goal the true neuroprotection. Very few companies are currently in this path. An even better approach would be to combine the above with memory enhancing capabilities probably with a drug that has multiple targets or with a combination of drugs.

{1}Forecasting the global burden of Alzheimer’s disease” published in Alzheimer’s & Dementia, July 2007, vol 3, no 3

{2}Saving Lives, Saving Money: Dividends for Americans Investing in Alzheimer Research. A report from the Lewin Group, commissioned by the Alzheimer’s Association. Washington, D.C.: 2004.

{3}Castellani et al., 2006, “Neuropathology of Alzheimer disease: pathognomonic but not pathogenic.” Acta Neuropathol, 111:503-509

{4}Castellani et al., 2006, “Antioxidant protection and neurodegenerative disease: The role of Amyloid-β and tau.” Am J Alzheimers Dis Other Demen. 21(2): 126-130

{5}Nunomura et al., 2006, “Involvement of oxidative stress in Alzheimer Disease.” J Neuropahtol Exp Neurol., 65(7):631-641.

{6}Davis et al., 1999, “Alzheimer neuropathologic alterations in aged cognitively normal subjects.” J. Neuropathol. Exp. Neurol. 58:376-388

{7}Ballard C.G. et al., 2007, “Cholinesterase inhibitors reduce cortical Abeta in dementia with Lewy bodies.” Neurology, 68: 1726-1729.

{8}Obrenovich et al., 2002, “Amyloid-b: a (life) preserver for the brain.” Neurobiol. Aging, 23:1097-1099

Source: PharmaFeed

Popularity: 49% [?]