Neurodegenerative disorders, such as Huntington’s disease (HD), Alzheimer’s disease (AD), and Parkinson’s disease (PD), are characterized by changes in the levels and activities of neurotrophic factors (NTFs), such as brain-derived neurotrophic factor (BDNF). Gain-of-function and loss-of-function experiments demonstrate in fact the linkage between wild-type huntingtin (HTT) and gene transcription and intracellular transport of BDNF. In the present chapter, we will analyze the involvement of BDNF in HD and other neurodegenerative diseases. We will discuss the current BDNF technologies focusing on stem cell therapies that induce BDNF upregulation, for instance, the method of autologous mesenchymal stem cell (MSC) culturing in the presence of cocktail of BDNF inducers and factors (MSC/BDNF), genetic engineering of MSC and their use as a vector for BDNF gene delivery, and combined method of establishment of embryonic stem cell (ESC)-derived BDNF-overexpressing neural progenitors, which is still at the preclinical stage. Clinical trial that uses MSC/BDNF is already in course, while genetic engineering of MSC/BDNF is in perspective to treat adult and juvenile HD. The potential application of these technologies is beyond HD. Other neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases also can be further included in the list of clinical trials that use MSC/BDNF or even ESC/BDNF-overexpressing neural progenitors.
Part of the book: Neurodegenerative Diseases
Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of CAG repeats in the huntingtin gene. The disease causes the progressive degeneration of neurons affecting particularly the medium spiny neurons (MSNs) within the striatum. The mHtt inclusions promote neurodegeneration. However, the mHtt can spread to different brain areas through exosomes. For this reason, it is not surprising that HD causes motor, cognitive and neuropsychiatric dysfunctions. To date there is no treatment able to modify the natural history of the disease. In this sense, the advanced cellular therapy, based on the therapeutic use of mesenchymal stem cells (MSCs) emerges as a potential candidate for HD treatment. This is because, the MSCs produce many critical therapeutic molecules which act in multiple cellular and molecular targets. Moreover, in addition, advanced cell therapy is a unique approach that could provides neuroprotection and neuroregeneration. However, the current discovery that the MSC mechanism of action is mediated by exosomes, have encouraged scientist to explore the therapeutic potential of the cell-free therapy. Based on this, we revisited the HD pathophysiology, areas. Providing evidence that MSC and MSC-derived exosomes can be used to change the natural history of HD.
Part of the book: From Pathophysiology to Treatment of Huntington's Disease