Our greatest limitation to treating Amyotrophic Lateral Sclerosis (ALS) is the lack of understanding what causes or enables sporadic ALS. However, the discovery of human-induced pluripotent stem cells (iPSC) has multiple implications; including helping us understand the disease’s mechanisms.
The ability to create stem cells from skin fibroblasts – cells of connective tissue that produces and secretes fibers e.g. collagen – could eliminate the need for using human embryos to derive human embryonic stem cells. This has important ethical implications for the scientific community.
By using adult human skin cells, we are now studying mechanisms causing the development of ALS using tissue samples, including motor neurons, astrocytes, microglia, oligodendrocytes, Schwann cells, and myocytes, from patients with the disease.
Johns Hopkins researchers are uncovering powerful skin cell discoveries for this progressive disease – primarily upper or lower motor neuron dysfunction – as well as other associated types, such as ALS with frontotemporal dementia. The development of iPSCs from ALS patients with newly identified genes can also provide a powerful tool for investigations into the similarities and differences between different genetic forms of ALS. In addition, iPSCs could also aid in the discovery of candidate drugs for ALS treatment.
We have only begun to scratch the surface in understanding what causes ALS, what factors influence the timing of disease onset, its progression, and its heterogeneity. Our direct involvement with patients in the Johns Hopkins ALS Clinic allows us to answer their questions such as why ALS starts with speech and swallowing problems in some patients, but with limb weakness in others, or, how environmental factors like toxins or traumatic injuries influence the onset of ALS.
How can stem cells speed discovery?
induced pluripotent stem cells derived from ALS
- Stem cells made from ALS patients and animal models of ALS can be directed into specific cell subtypes (astrocytes and motor neurons) to study what makes these cells vulnerable. Making stem cells from ALS patients with different kinds of ALS (i.e. those with trouble chewing and swallowing compared to those with arm and leg weakness) could allow us to understand how these cells respond differently.
- Stem cells made from ALS patients with hereditary ALS – the kind that is passed down in families – can be compared to those stem cells from ALS patients with “sporadic” disease – the kind which does not run in families – can help us understand how these forms of ALS differ.
- Stem cells from many ALS patients can be grown in a culture dish to discover what types of environmental factors or toxins influence cell survival.
- Stem cells made from ALS patients and animal models of ALS can be used to screen for drugs that may work to treat ALS (for example, astrocyte stem cells could be used to study drugs that improve the function of astrocytes resulting in neuroprotection. Motor neuron stem cells could be used to study drugs that could keep them from dying or enhance the growth of nerve processes).
To learn more about the Ansari ALS Center, please call 443-287-4341.
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To make an appointment with one of our specialists at the ALS Clinic, call 410-955-8511.