Optogenetics, the use of light to control the activity of suitably sensitized cells, has led to major advances in the field of basic neuroscience since it first emerged in 2005. Already, the technique has entered clinical trials for conditions such as Retinitis Pigmentosa. A major focus of interest is the use of optogenetics within the brain, where the ability to precisely control the activity of specific subsets of neurons could lead to novel treatments for a wide range of disorders from epilepsy to schizophrenia. However, since any therapy would require both the use of gene therapy techniques to introduce non-human proteins, and implantable electronic devices to provide optical stimulation, applying this technique in the brain presents a unique set of obstacles and challenges. This review looks at the reasons why researchers are exploring the use of optogenetics within the brain. It then explores the challenges facing scientists, engineers and clinicians wanting to take this technology from the lab into the first human brain, discussing different possibilities for a first-in-human clinical trial from a sponsor, patient and regulatory perspective.
With the general population reaching higher ages, a surge in Alzheimer's disease (AD) incidence will happen in the coming decades, putting a heavy burden on families and healthcare systems Worldwide. This emphasizes the pressing need for AD therapeutic interventions. Accumulating evidence indicates that inflammation is prominent both in the blood and central nervous system of AD sufferers. These data suggest that systemic inflammation plays a crucial role in the cause and effects of AD neuropathology. Capitalizing on our experience from a previous clinical trial with thalidomide, we hypothesize that modulating inflammation via the pleiotropic immunomodulator lenalidomide may alter AD if administered during a proper time window in the course of the disease. Thus, in this Phase II, proof-of mechanism study, 30 amnestic mild cognitive impairment (aMCI) subjects will be treated with lenalidomide at 10 mg/day for 12 months on a 1:1 ratio, followed by a 6 months washout period. The primary objective of this study is to investigate the effect of lenalidomide on cognition, which is assessed at regular intervals. The secondary objective is to assess the safety and tolerability of lenalidomide in aMCI patients evaluated through adverse events, vital signs, clinical biochemistry, and physical and neurological examinations. Tertiary objectives are to analyze the effects of lenalidomide on brain amyloid loads (Florbetapir PET imaging) and neurodegeneration (volumetric MRI) by comparing pre- and post-dosing data. Finally, exploratory objectives will investigate whether blood inflammatory markers can serve as surrogate markers of therapeutic efficacy. Our study should determine whether lenalidomide is safe in AD subjects and whether it can alter the clinical progression of AD when administered before dementia onset. If effective, lenalidomide would become the first drug capable of delaying the trajectory of AD, which could lead the way to find additional, less toxic treatments in the near future.
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