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2	14^th Annual ALS/MND Meeting Milan 2003 Largest meeting ever with over 700 participants Physicians, scientists, lay people Over 900 papers and abstracts Presentations divided into Joint Sessions, Basic science, and Clinical Sessions http://www.mndassociation.org
3	14^th Annual ALS/MND Meeting Milan 2003 Joint and Clinical Sessions
4	Epidemiology E. Beghi (Italy) May be an increasing incidence of ALS May be an increase in proportion of women Age peaks at 60-70
5	Epidemiology Stefano Belli (Italy) Italian professional soccer players 1960-1996 - 24,000 players 8 ALS patients v. 0.69 expected (X12 frequency) 38% <39 years, and 75% <59 5 more cases since 1996 [We are planning an epidemiological study in Dade County. Grant applications to ALSA and MDA.]
6	Cognitive Change in ALS Papers by Lomen-Hoerth (USA), Abrahams (UK), Olney (USA), Snowdon (UK) Especially in bulbar onset ALS Progressive Executive functions and language May play a role in decisions about accepting gastrostomy and non-invasive ventilation [Much of the change is very subtle. Research study of Dr. Grossman in UM.]
7	Psychological Impact of ALS Caregiver Burden Papers by Chio (Italy) and Goldstein (UK) Physical burden mainly lack of time for personal needs Psychological burden less if the caregiver has strong religious views [Despite much research, I do not think we have information that truly represents the Caregiver Burden.]
8	Depression in ALS Patients and Caregivers Paper by Alberts (NY) Prevalence much less than previously though using standard psychiatric measures (5-10%) [But reactive depression probably not captured. See ALS CARE report.]
9	CHANGES IN THE MANAGEMENT OF ALS SINCE THE PUBLICATION OF THE AAN ALS PRACTICE PARAMETER 1999. W.G. Bradley, F. Anderson, N. Gowda, R.G. Miller, and the ALS CARE Study Group
10	Changes in Management of ALS from ALS CARE Database ALS CARE Database started in 1996 6000 patients entered 175 from Kessenich Center Practice Parameter for management of ALS published by American Neurological Association in 1999
11	Changes in Management of ALS from ALS CARE Database 646 patients collected during the period May 2001 to November 2002, and 465 who died during the same period. The data were compared with similar information, where available, from the ALS CARE Database from 1996 through May 1999.
12	Most Valuable Sources of Information
13	Treatment of Depression
14	Severity and Treatment of Salivation
15	Use of Gastrostomy
16	Patients who Received NIPPV
17	Riluzole and Alternative Therapy Use
18	Reasons for Not Taking Riluzole May01-Nov02 Too expensive 28% Do not believe beneficial 21% Never heard of it 15% Stopped due to side effects 15% Doctor discouraged it 11% Concerned about side effects 11% Other 17%
19	Clinical Trials G. Groeneveld (Netherlands) Riluzole blood levels and outcome Those with higher blood levels Women Non-smokers Trend for better survival and strength With doses up to 300 mg/day could increase blood level X 1.7 Some fatigue and liver effects that decreased with time
20	Clinical Trials L. Mazzini (Italy) Intraspinal autologous mesenchymal (bone marrow) stem cells in ALS 5 patients No one showed signs of damage No benefit seen [No evidence that cells survive or function. Mazzini was severely criticized by Italian and USA physicians on ethical grounds.]
21	Clinical Trials Creatine trial (included UM) – negative Minocyline – Phase 2 trial in NY –active group rather worse than placebo (not significant), but will proceed to large Phase 3 trial (will not include UM) Tamoxifen – in the dose escalating phase at Madison, WI.
22	Clinical Trials NIH drug screen 1040 compounds (750 FDA and rest others) 29 in vitro assays (8 “ALS related”) Cephalosporins had multiple “hits” NorthEast ALS Trials Group (M.Cudkowicz, J.Shefner; includes UM) Ceftriazone (Rocephin) trial Intravenous injections twice daily into catheter Grant application submitted Stage 1 – 5 centers 60 patients Stage 3 – if goes that far involves UM
23	Basic Science Axonal transport Proteins dynein, dynactin, dynamitin provide energy shuttle to move materials up and down axon Mutations of the genes for these proteins cause motor neuron degeneration
24	Basic Science J.Glass (USA) The degeneration begins first in the distal nerve branches in the muscle and spreads proximally to the spinal cord in the SOD1 mouse Similar pattern seen in one early ALS patient
25	Basic Science D.Cleveland (USA), J-P.Julien (Canada) Studies of chimeras Mutant SOD1 protein in motor neurons alone not cause degeneration Need mSOD1 in motor neurons and glial cells 20% of normal glial cells can prevent degeneration [Possible role for stem cell treatment.]
26	Basic Science Protein aggregation SOD1 and other proteins are precipitated Interferes with metabolism of mitochondria, proteosomes, RNA transcription etc. Mobilize chaperon proteins, ubiquitin, heat shock proteins, etc Up-regulating HSP in SOD1 mouse improves survival
27	Basic Science Research on genes causing ALS ALS2 is juvenile onset ALS with autosomal recessive inheritance Gene codes for a GTPase protein involved in intracellular signaling, organization and transport of the cytoskeleton Making a mouse model by knocking out the gene
28	Basic Science NeuroImaging MRI with new FLAIR sequences can show the upper motor neuron degeneration in many cases MRS with 1.5 and 3T machines can show changes in neuron metabolites [UM has performed this research.] Transcranial Magnetic Stimulation with paired signals can show evidence of upper motor neuron dysfunction [TMS not allowed for clinical use in USA.]
29	14^th Annual ALS/MND Meeting Milan 2003 – In Summary Very busy meeting A great deal of new information exchanged New trials planned New research planned Next meeting in Philadelphia December 2-4, 2004 Remember it is open to lay people