Neurotrophic Factors to Combat Neurodegeneration

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Sammanfattning

Conditions caused by the lesion and progressive death of neuronal cells in the organism include neurodegenerative disorders and neuropathic pain. They represent the major causes of disability in Western countries. These conditions are more common in elderly people, and their prevalence, therefore, is expected to grow in the future because of the aging population. Currently, curative therapies against neurodegenerative disorders and neuropathic pain are not available. Existing treatments may provide temporary symptomatic relief to some patients but fail to stop neuronal degeneration, protect and restore damaged neurons. Neurotrophic factors are small secretory proteins whose main function is to support the survival of neurons. Therefore, they hold considerable promise for disease-modifying treatment of neurodegenerative disorders and neuropathic pain. However, despite promising results in preclinical studies, clinical translation of neurotrophic factors has so far achieved limited success. Neurotrophic factors are different from traditional chemical compounds used as drugs in the majority of cases, and this complicates their clinical use. Biology of neurotrophic factors and their absorption, distribution, metabolism, excretion, and pharmacokinetics properties dictate special requirements to clinical trials design. Patients taking part in clinical trials, delivery system, delivery paradigm, and the dose of neurotrophic factor should be carefully considered in trial design in order to ensure that the treatment will improve the condition of patients. In the present chapter, the author summarizes the available literature regarding signaling of neurotrophic factors, provides the data about their preclinical evaluation in animal models of neurodegenerative disorders and neuropathic pain, describes the results of clinical trials conducted with neurotrophic factors in patients, and discusses the limitations of these trials and translational problems faced by researchers and clinicians in this field. The author will further discuss emerging alternatives to neurotrophic factor proteins with improved translational perspectives, such as mutant proteins, small molecules, and peptides targeting the receptors of neurotrophic factors. The author will review attempts of clinical translation of glial cell line-derived neurotrophic factor family ligands for the treatment of Parkinson’s disease and neuropathic pain. The author will briefly describe the non-conventional cerebral dopamine neurotrophic factor tested in Phase I/II clinical trial in patients with Parkin- son’s disease. The author will also describe the data concerning the clinical evaluation of other neurotrophic factors in the above-mentioned conditions.

Originalspråkengelska
Titel på värdpublikationFrontiers in Clinical Drug Research - CNS and Neurological Disorders
RedaktörerAtta-ur Rahman, Zareen Amtul
Antal sidor56
Volym10
FörlagBentham Science Publishers, Ltd.
Utgivningsdatum2022
Sidor132-187
ISBN (tryckt)978-981-5040-68-5
ISBN (elektroniskt)978-981-5040-67-8
DOI
StatusPublicerad - 2022
MoE-publikationstypA3 Del av bok eller annan forskningsbok

Publikationsserier

NamnFrontiers in Clinical Drug Research - CNS and Neurological Disorders
Nummer10
ISSN (tryckt)2451-8883
ISSN (elektroniskt)2214-7527

Bibliografisk information

Publisher Copyright:
© 2022 Bentham Science Publishers.

Vetenskapsgrenar

  • 3124 Neurologi och psykiatri

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