Nonpatentable drugs and the cost of our ignorance

Molecular Endocrinology and Oncology Research Center, Laval University Medical Center (CHUL), and the Faculty of Pharmacy, Laval University, Sainte-Foy, Qué.
Canadian Medical Association Journal (Impact Factor: 5.96). 03/2006; 174(4):483-4. DOI: 10.1503/cmaj.050663
Source: PubMed
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Available from: Frédéric Calon,
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    • "As discussed above, demonstrating the clinical efficacy of n-3 PUFA in AD is faced with multifaceted challenges: (i) AD consists in a heterogeneous range of clinical entities, (ii) DHA and EPA are endogenous compounds with disease modification potential but limited symptomatic effects. The non-patentability of n-3 PUFA and complex manufactory processes arise as a further hurdle, which render private corporations less enthusiastic to invest in large prevention studies [121], and leave the funding burden to public entities. All these issues may turn out to be major obstacles to efficacy demonstration, compared to a patented synthetic compound applied to a disease with welldefined clinical endpoints. "
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    ABSTRACT: The current rise in the prevalence of Alzheimer's disease (AD) is unfortunately not matched by new treatment options. In the last 10 years, epidemiological, preclinical and clinical data have enlightened the possible preventive action of omega-3 polyunsaturated fatty acids (n-3 PUFA) in AD and other diseases. While the contribution of recent studies to our general knowledge is priceless, many important new questions have been raised. In the present review, we aim at addressing some of these timely interrogations. First, the transport of n-3 PUFA across the blood-brain barrier is underscored based on preclinical data. Second, the relative contribution of two neuroactive n-3 PUFA found in fish oil, docosahexaenoic acid (DHA; 22:6 n-3) and eicosapentaenoic acid (EPA, 20:5 n-3), remains unclear and is reviewed. Third, clinical trials on neurodegenerative diseases consistently remind us that treating early is critical, and this is likely to be the case with n-3 PUFA in AD as well. Fourth, we draw attention to the possibility that the current knowledge translation approach to make health recommendations might have to be adapted to non-patentable endogenous compounds like n-3 PUFA. We propose that answers to these critical questions will be instrumental toward a rational use of n-3 PUFA in AD.
    Current Alzheimer research 05/2011; 8(5):470-8. DOI:10.2174/156720511796391881 · 3.89 Impact Factor
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    • "Alternatively, n-3 PUFAs should also be studied for their potential symptomatologic effect as an add-on therapy to levodopa or other dopaminergic tools. Preclinical investigation would also help to better understand the mechanisms of action of n-3 PUFA and devise new patentable drugs by the development of new chemical analogs (Calon, 2006; Collins et al., 2008). "
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    ABSTRACT: Current epidemiological, preclinical and clinical data suggest that omega-3 polyunsaturated fatty acids (n-3 PUFAs) may constitute therapeutic strategy for several disorders of the central nervous system, including Parkinson's disease (PD). PD is a neurodegenerative disorder primarily characterized by motor symptoms but which also includes several other pathological features such as autonomic system failures, mood disorders, and cognitive deficits. Current pharmacological options for the disease are limited to symptom management and their long-term use leads to important side effects. In this review, we discuss the evidence for the effects of n-3 PUFAs in PD both from an epidemiological perspective as well as in light of data gathered on various pathological features of the disease. Effects of n-3 PUFAs on the dopaminergic system, α-synucleinopathy, their possible mechanisms of action as well as their therapeutic potential for PD patients are also reviewed. n-3 PUFAs are inexpensive, readily transferable to the clinical setting and their use could represent a neuroprotective strategy or a disease-modifying option to delay the appearance of symptoms. It could also be beneficial as a symptomatologic treatment or serve as an add-on therapy to current pharmacological approaches. Review of the current literature as well as the undertaking of future clinical trials will shed light on these possibilities.
    Ageing research reviews 03/2011; 10(4):453-63. DOI:10.1016/j.arr.2011.03.001 · 4.94 Impact Factor
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    • "Taken together, these data suggest that underconsumption of n-3 PUFA coupled to ingestion of high level of calories from fat, which are commonplace in our modern society, might increase the incidence of AD by accelerating its pathogenetic process (Calon and Cole, 2007; Calon, 2006; Pasinetti et al., 2007). Because the effects of dietary fats in AD remain very hard to demonstrate in clinical trials due to ethical and financial constraints (Calon, 2006), animal models of AD provide an opportunity to monitor precisely the intake of food in relation with subsequent alterations in brain markers of AD pathology. Since n-3 PUFA and total fats were the subject of separate studies, which were rather focused on A␤ pathology, we exposed the 3xTg-AD animal model of AD to n-3 PUFA deprivation alone (Diet B) or combined with a high-fat westernized diet (Diet C) to determine the quantitative impact of these precisely formulated diets on markers of A␤, tau and synaptic pathologies. "
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    ABSTRACT: To investigate potential dietary risk factors of Alzheimer's disease (AD), triple transgenic (3xTg-AD) mice were exposed from 4 to 13 months of age to diets with a low n-3:n-6 polyunsaturated fatty acid (PUFA) ratio incorporated in either low-fat (5% w/w) or high-fat (35% w/w) formulas and compared with a control diet. The n-3:n-6 PUFA ratio was decreased independently of the dietary treatments in the frontal cortex of 3xTg-AD mice compared to non-transgenic littermates. Consumption of a high-fat diet with a low n-3:n-6 PUFA ratio increased amyloid-beta (Abeta) 40 and 42 concentrations in detergent-insoluble extracts of parieto-temporal cortex homogenates from 3xTg-AD mice. Low n-3:n-6 PUFA intake ratio increased insoluble tau regardless of total fat consumption, whereas high-fat diet incorporating a low n-3:n-6 PUFA ratio also increased soluble tau compared to controls. Moreover, the high-fat diet decreased cortical levels of the postsynaptic marker drebrin, while leaving presynaptic proteins synaptophysin, SNAP-25 and syntaxin 3 unchanged. Overall, these results suggest that high-fat consumption combined with low n-3 PUFA intake promote AD-like neuropathology.
    Neurobiology of aging 11/2008; 31(9):1516-31. DOI:10.1016/j.neurobiolaging.2008.08.022 · 5.01 Impact Factor
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