Parallel Universes

Traditional Treatments vs
Emerging Disease-modifying Therapies
for Neuromuscular Disorders
MARCH
Day 1
25 Register for future
March 25, 2021 | Time: 1:00 PM EST – 4:00 PM EST
sessions or watch
x Lambert-Eaton myasthenic syndrome (LEMS)
 archived sessions
x Myasthenia Gravis

on-demand at:
 Amyotrophic Lateral Sclerosis (ALS) Current
Session NeuroSeriesLive.com

APRIL
Day 2
11 April 1, 2021 | Time: 2:00 PM EST – 4:00 PM EST
 Spinal muscular atrophy (SMA)
 Rett Syndrome

This activity is supported by educational grants from Acadia Pharmaceuticals Inc.; 1

Alexion Pharmaceuticals, Inc.; Biogen; Catalyst Pharmaceuticals; and Mitsubishi Tanabe Pharma America, Inc.
ALS
The Era of Disease-modifying Therapies

Presented by:

Terry D. Heiman-Patterson, MD
Professor of Neurology
Director Neurodegenerative Disease Center
Director MDA ALS Center of Hope
Temple University Lewis Katz School of Medicine

Amanda C. Peltier, MD, MS

Associate Professor of Neurology and Medicine
Vanderbilt University Medical Center

This activity is supported by educational grants from Acadia Pharmaceuticals Inc., Alexion Pharmaceuticals, Inc., 2
Biogen, Catalyst Pharmaceuticals, and Mitsubishi Tanabe Pharma America, Inc.
Faculty Disclosures

 Terry D. Heiman-Patterson, MD
− Consulting Fees: Biogen, Biohaven, Cytokinetics
Evolution Medical Communication, Evidera, ITF
Pharma, IQVIA, MTPA, Orphazyme, Samus
− Consulting: HMA Hospitals, MJH Holdings, Sate
of California Institute for Regenerative Med,
WebMD
 Amanda C. Peltier, MD, MS
− Other: HMA Hospitals, MJH Holdings, Sate of
California Institute for Regenerative Med, WebMD
3
Learning Objectives

 Identify patient characteristics and symptoms

that suggest a diagnosis of ALS so appropriate
testing can be performed to rule out mimicking
conditions and confirm a diagnosis
 Explain the therapeutic rationale of current and
emerging treatments for the management of
ALS
 Describe the importance of coordinated
specialized multidisciplinary ALS care and its
impact on quality of life and extended survival
4
Program Agenda

 Overview of ALS
− Spectrum of motor neuron disease
 Clinical Presentation and Diagnosis
− Early diagnosis
 Pathophysiology and Genetics
− Informing the future of therapeutics
 Current Management
− Multidisciplinary care
− Disease-modifying agents
 Emerging Therapies
− Challenges
− Hope

5
Overview of ALS
Spectrum of Motor Neuron Disease
ALS: A Motor Neuron Disease
 Upper motor neuron (UMN):
- Primary lateral sclerosis (PLS)
- FSP (>30 genetic variants)
- Bulbar palsy
 Lower motor neuron (LMN):
- Spinal muscular atrophy
- Motor neuropathy with conduction
block
- Kennedy’s disease
- Progressive muscular atrophy
 UMN and LMN:
- ALS
• Sporadic
• Hereditary: ALS (34 genetic
abnormalities identified)
• Bulbar palsy

FSP = familial spastic paraplegia or paraparesis; ALS = amyotrophic lateral sclerosis 7

Epidemiology

 Annual incidence of about 1-2 per 100,000

 Prevalence of about 3-5 per 100,000
 Male-to-female ratio of about 1.3:1
 Cumulative lifetime risk is 1 in 400
 Age of onset:
− Mean age is 54 years old
− Majority of cases are 45-70 years (range = 17-80 yrs)
− Genetic variants are younger
 Occupational clusters
− Gulf War and military service
 Familial ALS (FALS): 5%-10%

Robberecht W et al. Nat Rev Neurosci. 2013;14(4):248-264. Chiò A et al. Neuroepidemiology. 2013;41(2):118-130.
Johnston CA et al. J Neurol. 2006;253(12):1642-1643. 8
Clinical
Presentation and
Diagnosis

Early Diagnosis
Audience Polling Question

How confident are you in your

ability to diagnose ALS?

A. Very confident
B. Confident
C. Not confident

10
Amyotrophic Lateral Sclerosis

 Symptoms
− Fatigue, weakness, and stiffness
 Exam features
− UMN: Spasticity, hypereflexia, and spread of
reflexes, abnormal reflexes (Hoffman, Babinski,
jaw jerk)
− LMN: Muscle atrophy, weakness, and
fasciculations
 Progression
11
Diagnosis

Patient Story
ALS is a Heterogeneous Disease

 Site of focal onset:

− Legs (lumbar onset)
− Hands (cervical onset)
− Tongue, pharynx (bulbar onset)
 Age of onset:
− Mean age is 54 years old
− Majority of cases are 45-70 years (range = 17-80 years old)
 Progression:
− Variable
− SOD1 mutation: G93A is rapid, A4V is slow
− Can have “quiet periods”
 Survival:
− Variable
− 10% >10 years

13
Other Signs and Symptoms

 Clinically, it is a pure motor neuron syndrome

 Sensory symptoms (18%)
 Cognitive changes (50%) from FTD (5%-10%) to
ALSci/ALSbi
 Bladder and bowel dysfunction (30%)
 Ocular palsy (rare)

FTD = frontotemporal dementia

Rosenfeld J et al. Neurotherapeutics. 2015;12(2):317-325.

14
Differential Diagnosis
 Predominantly LMN  Predominantly UMN
− Cramp fasciculation syndrome − Primary lateral sclerosis
− Motor neuropathies (heavy − Multiple sclerosis
metals, porphyrins, genetic) − Leukodystrophies
− Multifocal motor neuropathy − Mass lesion
with conduction block
− Hydrocephalus
− CIDP
− HTLV1
− Kennedy’s disease
− Lyme disease
− SMA type 4
− HIV
− PMA
− Cervical myelopathy
− Polio and post-polio syndrome
− Combined system disease
− Paraneoplastic syndromes
− Mononeuritis multiplex,
radiculopathies
LMN=lower motor neuron; UMN=upper motor neuron; CIDP=chronic inflammatory demyelinating polyneuropathy;
SMA=spinal muscular atrophy; PMA=progressive muscular atrophy
15
Differential Diagnosis (cont)
 Bulbar  Muscle mimics
− Progressive bulbar palsy − Inclusion-body myositis
− Basilar meningitis − Isaacs syndrome
− Myasthenia gravis − Hyperparathyroidism
− Brainstem structural (vascular, − Polyglucosan
tumor)
− Kennedy’s disease
− Syringobulbia
 UMN and LMN
− Myelopathies (cervical spine, B12)
− HIV
− Lyme disease
− Syphilis
− Adrenomyeloneuropathy
− Hyperthyroidism
− Tay-Sachs disease
16
Diagnostic Work-up

 Exclude all other possibilities that may cause these

clinical symptoms
 Electrodiagnostic test
 Neuroimaging of the brain and spinal cord
 Laboratory studies
− Genetic testing
− B12, folate, HIV, HTLV1, Lyme, TFTs, RPR, PTH, heavy
metals, Ach R ab, sensorimotor panel, IPEP, SED, CRP
 Spinal-fluid examination
 Muscle/nerve biopsies
17
Diagnostic Delay is Common

 The time to diagnosis is variable

 Median diagnostic time 11.5 months (n=304)
− Longer if: >60 years, sporadic, spinal
− Fasciculations, dysarthria, leg weakness shorter time
 52% had an alternative diagnosis prior to ALS dx
− Neuropathy, spine disease, stroke, NMJ, neurodegenerative
disease, ENT, muscle disease
 Average of 3 physicians were seen before ALS diagnosis
confirmed
 Timely referral may improve diagnostic timing

Paganoni S et al. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15(5-6):453-456.

Palese F et al. Amyotroph Lateral Scler Frontotemporal Degener. 2019;20(3-4):176-185. 18
Implications of Diagnostic Delay

 Delay in treatment
− Disease modifying
− Supportive care
 Lost opportunities for clinical trials and study of early
disease

19
Pathophysiology
and Genetics

Informing the Future of

Therapeutics
Familial ALS
A Window into Pathophysiology
 10% of all patients have familial ALS (fALS)
− Approximately 15% with a Cu/Zn superoxide dismutase
gene mutation on chromosome 21
− Mechanisms by which alterations in SOD1 cause ALS
are unknown but there appears to be a toxic gain of
function
 More than 34 additional genes implicated accounting
for more than 70% of fALS
− New insights, new heterogeneity, new targets
− Most common of all: C9ORF72

21
More than 25 Different Mutated Genes
Associated with ALS

22
Gene Discovery in ALS/MND

>70% of fALS is attributable to known variants

Boylan K. Neurol Clin. 2015;33(4):807-830. 23
Genetic Overlap with Frontotemporal
Dementia

ALS
FTD
VCP
CHMP2B
TDP43
FUS
SOD1
UBQLN2
MAPT hnRNPA1
C9ORF72
GRN NEK1
CHCHD10
OPTN
TBK1
CCNF
TIA1

Couratier P et al. Rev Neurol (Paris). 2017;173(5):273-279.

24
 Diverse Neuronal Gene Defects Impair Function in Motor
Neurons in ALS/MND.
RNA
HNRNPA1 Protein Processing
Astrocytes UBQLN 1 and 2 Endoplasmic Reticulum
SOD1 SQSTM1 SIGMAR1
OPTN
VCP

Nuc

SOD1
Aggregates M

Microglia
GEF
Signalling Nucleus-DNA Vesicle BP Mitochondria Enzymes Motors Cytoskeleton
SETX
FUS Spastin ALS
Alsin VABP SOD1 SOD1 Dynactin
TDP43 Peripherin
ATX2
C9ORF72 NEFH
TAF15
ELP3
ALS
Pathophysiology
 Informed by genetics and
sporadic ALS research
 10 implicated pathways
− Nucleocytoplasmic transport
− RNA and DNA metabolism
− Protein handling
− Mitochondrial function and
oxidative stress
− Oligodendrocyte and
microglial function
− Cytoskeletal and axonal
transport
− Vesicle transport
− Excitotoxicity

Ingre C et al. Clin Epidemiol. 2015;7:181-193. 26

Van Damme P et al. Dis Model Mech. 2017;10(5):537-549.
Current
Management

Multidisciplinary care
Disease-modifying Agents
Impact on
Relationships
Patient Story
Audience Polling Question

Disease modifying therapies

exist for ALS…

A. Yes
B. No
C. Not sure

29
Treatment of ALS

 Compassion and hope

− Giving the diagnosis and prognosis
− Managing the disease – palliative care
• Goals of palliative care: relieve suffering, QoL,
continuum, appropriate for all stages of disease and
for curable and incurable, multidisciplinary
− Terminal care
 Education
 Multidisciplinary

30
Treatment of ALS (cont)

 Multidisciplinary approach
− PT/OT
− Speech
− Nutrition
− Psychotherapy
− Respiratory
− Nursing
− Research
 Symptom management
 Disease modification
31
PT/OT Evaluation
 PT  OT
− Muscle strength − Functional ADLs
− Tone • Eating
− Flexibility • Dressing
− Coordination • Writing
− Balance • Recreational

− Mobility − Range and splinting

• Ambulation − Home evaluation
• Wheelchair
• Transfers
 Equipment
− MAFOs
− Ambulatory assistive devices
− Wheelchairs
− Pressure-relieving cushions
− Transfer assist devices
− Hospital beds 32
Assistive Technology

33
Symptom Management

 Improving symptom management is an unmet need*

 Dysphagia (swallowing difficulty)
− Swallowing strategies
− Diet changes
− PEG
 Dysarthria (speech difficulty)
− Articulation strategies
− AAC
 Respiratory problems
− Noninvasive and invasive ventilation

*Nicholson K et al. Muscle Nerve. 2018;57(1):20-24.

34
 Symptoms in ALS

Frequency of Symptoms in ALS Patients Frequency Symptoms Bothered Patient

MUSCLE CRAMPS MUSCLE CRAMPS
FASCICULATIONS FASCICULATIONS
STIFFNESS STIFFNESS
DEPRESSION DEPRESSION
FATIGUE FATIGUE
CONSTIPATION CONSTIPATION
DIFFICULTY SLEEPING DIFFICULTY SLEEPING
SIALORRHEA SIALORRHEA
ANXIETY ANXIETY
DRY MOUTH DRY MOUTH
THICK PHLEGM THICK PHLEGM
LABILE AFFECT LABILE AFFECT
URINARY URGENCY URINARY URGENCY
LARY NGOSPASMS LARYNGOSPASMS

0 20 40 60 80 0 20 40 60 80 100
Percent With Symptom Percent Bothered

35
Overall Symptom Management
Symptom Physical Intervention Medication
Constipation Fluids, fiber, fruit Bisacodyl, polyethylene glycol, MOM, lactulose

Amantadine, methylphenidate,
Fatigue Rest, treat OSA if present
dextroamphetamine, pyridostigmine, if OSA-NIV
Amitriptyline, trazodone, melatonin, diphenhydramine,
Sleep difficulties Sleep hygiene
benzodiazepines, NIV

Dry mouth Fluids, medication review, candy

Sialorrhea Suction machine Anticholinergics, onabotulinumtoxinA, irradiation

Thickened secretions Hydration, suction, coughalator Guaifenesin, nebulizer

Stiffness ROM, stretching, massage, pool Tizanidine, baclofen

Depression Counseling Antidepressants (SSRI, SNRIs, tricyclics)

Positioning, stretching, massage, Magnesium, vitamin E, gabapentin, pregabalin,
Cramps
pool tizanidine, benzodiazepine

Labile Affect Dextromethorphan/quinidine, amitriptyline, sertraline

Anxiety Counseling, biofeedback, meditation

Urgency Toileting schedule Oxybutynin

Laryngospasm Benzodiazepine (sublingual)

Fasciculation Baclofen, gabapentin

Jackson CE et al. Neurol Clin. 2015;33(4):889-908. Anderson PM et al. J Neurol. 2012;19(3):360-375. Miller RG et al. Neurology. 2009;73(15):1227-1223.
Galvez-Jimenez N. UpToDate. 2018. Symptom Based Management of Amyotrophic Lateral Sclerosis. 36
Available at: www.uptodate.com/contents/symptom-based-management-of-amyotrophic-lateral-sclerosis.
Respiratory Failure

 Inspiratory muscle weakness

− Decreased alveolar ventilation resulting in ↑ CO2
− Microatelectasis
 Expiratory muscle weakness
− Decreased cough and secretion clearance
 Upper airway weakness
− Decreased gag reflex
− Aspiration
− Upper-airway obstruction
− Malnutrition

37
Respiratory Management

 Follow pulmonary function tests (PFTs)

−  MEP and MIP
−  MVV
−  FVC
 Include respiratory symptoms in HPI
− dyspnea, fatigue, daytime somnolence, confusion, orthopnea,
morning headaches, yawning
 Pneumococcal and influenza vaccines
 PEG
 Aspiration
 Acute infections
 Control secretions
 Ventilation
38
Secretion Control and Reduction of
Aspiration
 Secretion control
− Secretion can lead to plugging, atelectasis, and infection
− Treatments aimed at decreasing secretion and thinning
secretions
• Anticholinergics, guaifenesin, botulinum toxin, radiation
− Treatments aimed at clearance
• Peak cough flows (160 L/min necessary, intervene at
270 L/min)
• Suction, chest percussion, vest, insufflator-exsufflator, tracheostomy
 Aspiration management
− Elevate the head of the bed
− Wedge pillow
− PEG tube

39
Non-invasive Intermittent Positive
Pressure Ventilation (NIPPV) in ALS
 Reversing fatigue and hypoxia

 Beneficial effect on upper-airway dysfunction by

“splinting open” the vocal cords and upper airway,
thereby decreasing work of breathing and preventing
respiratory muscle fatigue

 Improves lung compliance, possibly by re-expanding

areas of microatelectasis

 Preventing nocturnal hypoventilation may prevent the

blunting of the central ventilatory drive that occurs with
hypercapnia
40
Disease-modifying Therapy: Riluzole

 Inhibits release of pre-synaptic glutamate; blocks post-

synaptic effects by non-competitive blockade of NMDA
receptors
 Prolongs survival in ALS mouse model
 Four trials examined tracheostomy-free survival
− 974 riluzole-treated patients and 503 placebo-treated patients
− Riluzole 100 mg per day provided a benefit
− Overall, 9% gain in probability of surviving one year
(49% placebo vs 58% riluzole)
− Increased median survival from 11.8 to 14.8 months
− Small beneficial effect on both bulbar and limb function
 Fatigue, nausea, and increase in liver-function tests
Fehlings MG et al. Spinal Cord. 2016;54(1):8-15. Bensimon G et al. N Eng J Med. 1994;330(9):585-591.
Miller RG et al. Cochrane Database Syst Rev. 2012;(3):CD001447. Fang T et al. Lancet Neurol. 2018;17(5):416-422. 41
Disease-modifying Therapies:
Edaravone
 Antioxidant free radical scavenger
 Ph2 open-label 24 weeks-30 mg and
60 mg – 60 mg showed decreased
nitrotyrosine in CSF
 Ph3 60 mg IV randomized double-blind*
− ALSFRS decline was primary endpoint
with 12-week lead-in
− 246 subjects with 100 drug-treated
− Decreased the decline of ALSFRS score
(5.7 vs 6.35) but not significantly
− Repeated ph3 to look at early population
and significant decrease (7.5 points vs
5.01 points) in double-blind trial over 6
months (FVC>80%, onset <2 years)**

*Writing Group et al. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18(sup1):40-48.

**Writing Group et al. Lancet Neurol. 2017;16(7):505-512
42
Edaravone: Adverse Events

 Hypersensitivity
 Sulfite allergic reactions
 >10% (treated/placebo)
− Contusion (15%/9%)
− Gait disturbance (13%/9%)
 1%-10%
− Headaches (10%/6%)
− Dermatitis (8%/5%)
− Eczema (7%/4%)
− Respiratory failure, hypoxia (6%/4%)
− Glycosuria (4%/2%)
− Tinea (4%/2%)

Radicava [edaravone] prescribing information. Jersey City, NJ: Mitsubishi Tanabe Pharma Corporation; 2018.
Available at www.radicavahcp.com. 43
Management

Patient Story
Emerging
Therapies

Challenges and Hope

ALS Clinical Trials: What Are the
Challenges?
 Diagnosis is often delayed
 Variable presentation
 Genetic heterogeneity
 Variable progression and survival
 Enrollment and retention
− 22% of subjects withdraw
 Trial design complicated by
variability
− Target selection
− Inclusion criteria
− Endpoints
− Stratification-target responders
 Biomarker development
46
Choosing a
Target
 Genetic mutations
 Mechanisms of
disease

Ingre C et al. Clin Epidemiol. 2015;7:181-193.

47
Van Damme P et al. Dis Model Mech. 2017;10(5):537-549.
 Treatment Strategies: ALS Pipeline
 Anti-glutamate  Anti-oxidant
− Riluzole − Inosine
− Dextromethorphan/quinidine − Edaravone
− GM604
 Anti-apoptotic/neuroprotectant − RNS60*
− Methylcobalamin (Post hoc +) − CuASTM*
− Arimoclomol − Verdiperstat*
− Stem cells
− AMX0035**
− AMX0035**
− GM604  Other novel therapies
− Pimozide − Retigabine
− GDC-0134 − Mexiletine
− Pridopidine* − Biotin
− High-calorie diet
 Anti-inflammatory − CNM-Au8 (enhance bioenergetics)*
− Masitinib
− Ibudilast
− Treg and IL-2  Antiretroviral trials
− Immunosuppressives − Dolutegravir/abacavir/lamivudine
− RNS60* − Darunavir, ritonavir, dolutegravir, tenofovir,
− APL-2 and alafenamide (HERV-K)
− Ravulizumab  Gene modulation (SOD1/C9ORF72)
− Zilucoplan* − SOD antisense*
− Stem cells (?) − AAV10 silencing
 Protein C kinase inhibitor − Pyrimethamine
− Tamoxifen (also anti-apoptotic) − C9 antisense

*Included in the Platform Trial 48

**Successful phase II showing efficacy
Platform Trial

 Master protocol in which multiple treatments are evaluated

simultaneously
− Zilucoplan, verdiperstat, CNM-Au8, pridopidine
 Adaptive – dropping ineffective treatments, adding new ones
 More efficient
 Share placebo group

Conventional Trial Platform Trial

HEALEY ALS Platform Trial. NCT04297683. Clinicaltrials.gov.

49
AMX0035: Combination of PB and TUDCA
(Oxidative Stress and Mitochondria)
 HDAC inhibitor; up-regulates chaperones  Inhibits mitochondrial-associated apoptosis
  protection against oxidative stress and cell in in vitro and in vivo models
death in vitro and in vivo

PB TUDCA

Phase II
PB = sodium
phenylbutyrate

TUDCA = tauroursodeoxycholic Safety and

acid
tolerability

Decline in
ALSFRS R score
Paganoni S et al. N Engl J Med.
2020;383(10):919-930. 50
Tofersen: Targeting mSOD1

Anti-sense oligonucleotide that

blocks translation and reduces
SOD1 protein levels
Tofersen MOA[3]
 Phase I/II trials – 50 subjects
with SOD1 FALS1
− Randomized to placebo or 3
different doses of tofersen for
12 weeks
− Results:
• Safe; well-tolerated
• Significant reduction in CSF
mSOD1 levels
• Trend toward slowed
progression
− Next phase is now open2

1. Miller TM et al. N Engl J Med. 2020;383(2):109-119. 2. ClinicalTrials.gov. NCT02623699.

3. Askari FK et al. N Engl J Med. 1996;334(5):316-318. 51
Pyrimethamine: Targeting mSOD1

 Discovered via high-throughput

drug screening
SOD1 content at 18 weeks of treatment
 Previously ID as an anti-malarial according to mutation type
drug

 Open-labeled trial: 32 patients

with familial ALS and SOD1
mutations

 Results:
− Reduction in CSF mSOD1
− Slower clinical disease
progression than predicted

Lange DJ et al. Ann Neurol. 2017;81(6):837-848.

52
Arimoclomol: Targeting mSOD1

 HSP-70-inducer: helps
misfolded/aggregated Quality Control Pathways Influenced
proteins by Altered HSP-70[3]

 Randomized, placebo-
controlled trial: 38 patients
with familial ALS[1]
 Results:
− Good safety and tolerability
profile
− Beneficial trend in
progression and survival
 Larger, inclusive phase III
trial completed; results
pending[2]
1. Benatar M et al. Neurology. 2018;90(7):e565-e574. 2. ClinicalTrials.gov. NCT03491462.
3. Kalmar B et al. Pharmacol Ther. 2014;141(1):40-54.
53
Genetic Mutations: C9orf72 ALS

 Hexanucleotide repeat expansion located on chromosome 9

 Most common identifiable cause of ALS
− Accounts for 5% to 7% of all cases
− Mechanism of pathophysiology is still under debate: LoF vs toxic GoF?

Cappella M et al. Int J Mol Sci. 2019;20(18):4388. 54

C9orf72 as a Therapeutic Target
 BIIB078: ASO  Metformin (blocks RAN protein
− NCT03626012[1] synthesis = improved disease
• 90 subjects with C9orf72-ALS features)
• Single doses − NCT04220021[3]
• Each cohort gets higher dose • 19 subjects with C9orf72-ALS
• Safety, tolerability being • Increasing repeat doses; 24
examined weeks
• Safety, tolerability, CSF RAN
levels, and potential efficacy
 NCT04288856[2] being examined
• 90 subjects with C9orf72-ALS
• Multiple doses
• Safety, tolerability, effect on
disease progression being
examined

1. ClinicalTrials.gov. NCT03626012. 2. ClincalTrials.gov. NCT04288856. 3. ClinicalTrials.gov. NCT04220021.

55
Message to
Clinicians
Patient Story
Conclusions

 ALS is treatable
 Early diagnosis is critical to initiate both disease-directed care and
supportive/symptomatic treatment that will improve both QoL and
survival
 Be suspect in patients where there is:
− Painless progressive weakness/dysarthria/dysphagia
− Atrophy of affected area
− Sensation normal
− Increased reflexes
− No other explanation
− Early referral to a center
 The pipeline for new disease-directed treatments for both familial
and sporadic ALS is growing and testing has accelerated through
novel trial designs
57
Q&A
with the experts

58
Patient Advocacy
•Collaborates with local, state, and federal agencies on policies that
 Has supported the
encompass the needs of rare-disease patients
identification, treatment, and
Patient Organization Mentorship
cure of rare disorders for
•Supports the establishment and growth of disease-specific nearly 40 years
organizations so they can better serve their patients
 Partners with >300 disease-
Patient and Professional Education
•Educates patients and their families, physicians, and
specific patient organizations
other health care professionals about rare diseases
and their dedicated organizations  Access resources at:
Research Support • https://rarediseases.org
•Provides grants to facilitate rare-disease research and
establish disease-specific registries

Patient Assistance Program

•Offsets the costs of treatment, clinical-trial participation,
and access to services

International Partnerships
•Represents the US and collaborates with global partners dedicated
to addressing the global health challenge of rare diseases
59
 More Information and Support

http://www.mda.org/

http://www.alsa.org

https://www.alshf.org/

https://www.everythingals.org/ https://iamals.org/ 60
What’s Next in the 2021
Neuromuscular Series?
Available LIVE and Day 1
On-Demand Today at:
March 25, 2021 | Time: 1:00 PM EST – 4:00 PM EST
x 1:00pm
 Lambert-Eaton Myasthenic Syndrome (LEMS)
Earn up to 3 credits; x 2:00pm
 Myasthenia Gravis
CME/CE-certified x 3:00pm
 Amyotrophic Lateral Sclerosis (ALS)

Day 2
Available LIVE and
April 1, 2021 | Time: 2:00 PM EST – 4:00 PM EST
On-Demand at:
 2:00pm Spinal Muscular Atrophy (SMA)
 3:00pm Rett Syndrome
Earn up to 2 credits;
CME/CE-certified

61
Join us for Our Next Session

SMA: Early Detection to Enhance Access to Genetic

Testing and Disease-modifying Therapies
Thursday, April 1st from 2:00PM – 3:00PM EST

Speakers
Julie A. Parsons, MD
Haberfeld Family Endowed Chair in Pediatric
Neuromuscular Disorders
Professor of Clinical Pediatrics and Neurology
University of Colorado School of Medicine
Children’s Hospital Colorado
David N. Lieberman, MD, PhD
Attending Child Neurologist
Assistant, Department of Neurology
Instructor of Neurology, Harvard Medical School
Boston Children’s Hospital
Department of Neurology

62
Thank you for
participating today!

Visit NeuroSeriesLive.com for Additional Live and

Endured CME/CE Neurology Activities.