ALS By Arjun Puri and Navdeep Saini

Intro Amyotrophic Lateral Sclerosis Neurodegenerative disease Incurable and fatal Can affect anyone Life expectancy = 2-5 years

Etiology Sporadic – unknown Familial – chromosome 21, autosomal dominant Mutations: SOD1, TARDBP and FUS, C9orf7 Environmental risk factors Smoking, military services, sport Western Pacific: Cycad nut Glutamate

Epidemiology 2 deaths per 100,000 annually West Pacific: Guam (143 cases per 100,000 Kii peninsula of Japan New guinea Incidence rate: 2 per 100,000 people Prevalence rate: 6-8 per 100,000 people 2000 census = 22,600 Americans (prevalence) Finland = highest rate

Clinical Research 20% physician-assisted suicide (Netherlands) Spiritual care and bereavement comforts ppts.

Clinical Research (Cont.) Palliative care STUDY: 171 ppts: 90% died peacefully (no mechanical vent. Slipped from sleep to coma due to hypercapnia) Dyspnea treated with Morphine (2·5–5·0 mg orally or 1–2 mg subcutaneously or intravenously every 4 h) Oxygen admin. if signs of hypoxia lorazepam sublingually (beginning with 1·0–2·5 mg) or midazolam orally or subcutaneously (starting at 1–2 mg)

Treat the symptoms, not just the disorder!!!

Diagnostic Markers Spirometry – progression of ALS in clinical trials (contraInd. Prominent bulbar involvement) Maximum voluntary isometric contraction better to achieve objective measure of muscle strength (contraInd. Only fit individuals and depends on observer training) neurophysiological index is easily calculated from standard data obtained when calculating motor conduction velocity

Clinical Trials Adenoassociated virus exp. IGF-1 into G39A SOD1 transgenic mice – injected into resp. and limb muscles. Prolonged survival even when clinical features of ALS have appeared. Lentiviral inj admin. Once exp. EDGF delayed onset & slowed down progression, even when paralysis was present.

Stem Cell Therapy replacement of lost cells, cell fusion, neurotrophic factor release, endogenous stem-cell proliferation, Transdifferentiation All under research, however ethical dilemma

Conclusion Incr easingly important to develop new treatment strategies Drug delivery via intrathecal admin or viral vector (additional silencing mutant gene) Will remain progressive for multiple years – decades, importance of palliative care (  QoC)

References /article/ /article/ Mitchell J.D., Borasio G.D,: Amyotrophic lateral sclerosis: Lancet; 369: 2031–41: 2007 Lou Gehrig: The Iron Horse of Baseball