The past, present and future of stem cell clinical trials for ALS

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder that is characterized by progressive degeneration of motor neurons in the cortex, brainstem and spinal cord. This leads to paralysis, respiratory insufficiency and death within an average of 3 to 5 years from disease onset. While the genetics of ALS are becoming more understood in familial cases, the mechanisms underlying disease pathology remain unclear and there are no effective treatment options. Without understanding what causes ALS it is difficult to design treatments. However, in recent years stem cell transplantation has emerged as a potential new therapy for ALS patients. While motor neuron replacement remains a focus of some studies trying to treat ALS with stem cells, there is more rationale for using stem cells as support cells for dying motor neurons as they are already connected to the muscle. This could be through reducing inflammation, releasing growth factors, and other potential less understood mechanisms. Prior to moving into patients, stringent pre-clinical studies are required that have at least some rationale and efficacy in animal models and good safety profiles. However, given our poor understanding of what causes ALS and whether stem cells may ameliorate symptoms, there should be a push to determine cell safety in pre-clinical models and then a quick translation to the clinic where patient trials will show if there is any efficacy. Here, we provide a critical review of current clinical trials using either mesenchymal or neural stem cells to treat ALS patients. Pre-clinical data leading to these trials, as well as those in development are also evaluated in terms of mechanisms of action, validity of conclusions and rationale for advancing stem cell treatment strategies for this devastating disorder.

Ex vivo differentiation of human bone marrow-derived stem cells into neuronal cell-like lineages

“…19 However, before SC therapy can be applied in a clinical setting for any of the neurodegenerative disorders, intensive research must be completed to fully understand SC behavioral changes and interaction when placed in a neurological physiological microenvironment that mimics the original body environment.…”

Restoring motor function using optogenetics and neural engraftment

“…In the absence of conventional therapies to restore lost motor function in ALS and SCI, stem cell based strategies have provided a promising avenue of research to overcome paralysis [4]. Early evidence of lifespan extension in transgenic rodent models of ALS following intraspinal transplantation of human neuronal precursor cells (hNPCs) [5] has recently progressed to Phase 1 clinical trials in ALS patients, and has proven to be safe and well tolerated [6].…”

Amyotrofik lateral skleroz: klinik özellikler ve güncel tedavi yaklaşımları

“…Ailesel vakalarda hastalığın genetik zemini iyi anlaşılmaya başlansa da halen altta yatan patoloji bilinmemektedir ve efektif tedavisi yoktur. Neden bilinmediği için tedavinin şekillendirimi de zorluk teşkil etmektedir 24 . Özellikle FTD olmak üzere nörodejeneratif hastalıklar ile klinik ve patolojik birliktelik söz konusudur1.…”

“…Fonksiyonel kapasiteyi idame ettirmek ve artırmak amacı ile aerobik egzersiz; kognisyonu artırmak amacı ile kognitif davranışscı terapi etkindir 24 .…”