Part 2:The A to Z on Amyloidosis (Heart, Nerves, Nervous System, Ocular, Latest Technology, Therapy)

Part 2:The A to Z on Amyloidosis (Heart, Nerves, Nervous System, Ocular, Latest Technology, Therapy)

(Amyloidosis Support Group, October 2019, Conference Notes)


Our heart consists of millions of muscle cells making it beat. Amyloid gets between the cells, making the heart muscles stiffer.
This leads to extra fluid in lungs.
Shortness of Breath
Swelling (edema)
Unable to lie down due to shortness of breath (from fluid in lungs)
Waking up gasping for air
Cough, often at night
Heart Rhythm problems (Arrhythmias)
Bradycardia – heart beats too slow – may need pacemaker
Tachycardia – heart beats too fast
Atrial fibrillation – irregular rhythm from upper chambers
Electrical shock (cardioversion)
Risk of blood clot – stroke – need blood thinners
Defibrillator – for arrhythmias from ventricles
Medications used for other type of heart failure often not helpful:
beta-blockers, ACE-inhibitors
Individualised treatment
Follow-up for Cardiac Amyloid
How do you feel?
How far can you walk?
How often have you been hospitalized?
Are you requiring more diuretic?
What do simple blood tests show? Troponin, NT-BNP (BNP), creatinine

Cardiac Amyloid – What can you do

Make sure you have the right diagnosis
Weigh yourself everyday – look out for fluid
Use compression stockings, if needed
Limit your salt and fluid
Exercise – go at your own pace but get moving
Do some light strength training
The heart likes to pump to muscle not flab
What should patients and caregivers do?
Keeping your whole body healthy is crucial
Eat, Move, Sleep!
Eat: 5 Fruits/Veggies per day
Move: At least 10 minutes per day
Sleep: Eight hours for most
Cardiac Amyloidosis – Summary
Amyloid – stiff heart – hard to fill
Heart Failure and Rhythm problems
Heart function is complex – a single number does not tell you how your heart is doing
Track your numbers
Steps and Reps!
Nerves and Neuropathy
Janice Wiesman MD, FAAN
Clinical Associate Professor of Neurology New York University School of Medicine Adjunct Assistant Professor of Neurology Boston University School of Medicine
What is a nerve?
A nerve is a cable-like bundle of axons that runs between the spinal cord and the periphery.
Axons transmit information by an electrical current that runs along the axon like a wire in your home, like electricity running through a wire in your home.
The axons are each surrounded by a fatty coating, called myelin, that acts like insulation on a wire.
What is an axon?
An axon is the arm-like extension of a nerve cell (neuron)
Neuron types:
o motor,
o sensoryand o autonomic
The neurons are located in or near the spinal cord.



Where do nerves come from?
Nerves come from the brain, through the spine, to spots throughout your body
What do nerves look like?
There are 3 kinds of axons
Motor – information goes out to muscles
Sensory – information comes in from skin, joints, muscles, organs etc. Autonomic – governs “automatic functions”
Motor Axons
Motor neurons sit in the spinal cord and send out axons to contact muscle cells
When the motor neuron fires an electrical impulse, the impulse races down the axon and the end of the axon releases a chemical, called a neurotransmitter, that causes the muscle cell to contract.
Sensory Axons
Sensory neurons sit just outside the spinal cord and send one long axon out to the skin and organs and one short axon into the spinal cord.
Sensory axons bring information from the skin and organs to the spinal cord and up to the brain so we can feel, hear, taste, smell, see and know where are limbs are in space.
Autonomic Axons
The cells bodies that make these axons sit in the spinal cord and brainstem and send out axons that contact:
Salivary glands in the mouth
Tear glands in the eye
Muscle in the wall of the stomach and intestine
Sweat glands in the skin
Muscle in the wall of blood vessels, Including those in the genitals
(Autonomic nerve symptoms often come 1st in amyloidosis)
Different axon types are different sizes
Autonomic axons are the thinnest
Sensory axons
o Thinnest mediate pain and temperature
o Thickest mediate pressure, vibration and joint position sense
Motor axons are the thickest with the thickest myelin coat – 60m/sec
Nerve Damage in Amyloidosis
Can be one nerve, e.g., Carpal tunnel syndrome
Can be nerve roots as they emerge from the spine: Radiculopathy (“pinched nerve”)
Can be generalized disorder of nerves, e.g., Polyneuropathy = peripheral neuropathy
Amyloid Polyneuropathy
Axonal, length-dependent, symmetrical, dying-back neuropathy
• Axon itself is damaged by amyloid
o Compression of axons by amyloid deposits
o Amyloid compresses blood vessels that supply nerves o Metaboliccomponent
• Longest nerves affected first – why?
o Motor neurons are longest, like 3ft long leg nerve. The same one you were born with. Extremely thin. So a small amount of damage in each inch of nerve can have notable cumulative effect.
•Thinnest axons affected first, thicker axons are affected later
•The nerve degenerates from the end, upward
Nerve with amyloid- the amyloid compresses the axons.
Symptoms of Polyneuropathy
Sensory Symptoms
– Tingling, numbness, burning, feeling cold, feeling like walking on cotton/something in your shoe.
– Feeling off-balance when closing your eyes.
– Start in feet, slowly climbs up the legs. When the symptoms are at knee level may have symptoms in the hands.
– Often feel worse at night.
– Off your feet, no pressure from walking.
Why does it feel numb and painful at the same time?
Different axons mediate different sensations,
•Thin axons mediate pain sensation
o When damaged, they fire at random – brain “feels” it as pain
• Thick axons mediate touch and pressure sensation
o When damaged, do not transmit information to the brain – so brain does not “feel” touch
Motor Symptoms
• Weakness
Starts in feet
Weakness in hands
o Think about carpal tunnel syndrome
Atrophy of muscle
Restless legs
Autonomic Symptoms
• Dry eyes and mouth
o Nerves to the lacrimal and salivary glands are damaged
• Trouble accommodating to bright light
o Autonomic nerves control constriction of the pupil
• Lightheadedness when standing
o Autonomic nerves make your blood vessels constrict and your heart rate increase when you stand up
• Skin and nail changes
o Shiny, dry skin with hair loss
Erectile dysfunction in both the penis and clitoris
Decreased vaginal lubrication
Treatment of Polyneuropathy
Questions people ask:
Is my underlying disease being treated? There are some treatments now.
Is there treatment to make nerves grow back? Not yet.
How do I treat symptoms?
Then I (the doctor) ask – Do you want treatment?
• Is it making you crazy?
If I am treated will my nerves grow back?
Nerves regrow best in people who are young and otherwise healthy
Nerves grow back slowly: 1 mm a day = 1 inch a month = 1 foot a year
Can I treat the numbness?
Not much can be done.
While pain and tingling can be treated, there is no treatment for the numbness
“Tincture of time” – may get better over time
Symptomatic treatment of sensory symptoms
Without Medication
Foot rub or warm water foot massage before bed
Acupuncture (but check with your doctor regarding risk of infection!!!)
Anodyne light therapy and cold laser
o Increase blood flow and make feet feel better – expensive
Use of compression socks – stimulates nerves, con override the random pulses from amyloidosis
Transcutaneous nerve stimulation
o May or may not help, can be done at home. Studies disagree on effectiveness, but not it’s pretty harmless.
• Percutaneous nerve stimulation
o Someliteraturesupportsthis o Done in the office
Topical Medication
Lidoderm cream or patch – topical anesthetic
Aspirin-like creams (diclofenac)
Menthol cream ( Ex. Ben Gay)
Capsaicin cream
o initiallyincreasespain,mustbeused2-4times/day
Capsaicin patch (Qutenza and generic)
Botulinum toxin injected into the top of the feet in a grid
Anti-seizure medications
o Lyrica(pre-gabalin)
o Neurontin(gabapentin)
o Cymbalta(duloxetine)
o “tricyclic antidepressants” like Elavil (amitriptyline) – not typically used in amyloid – may compound other symptoms
o Aspirin-likedrugs
o Tylenol
Long acting narcotics are usually not appropriate for the treatment of nerve pain.
What about marijuana?
There are studies that show benefit of smoked cannabis for pain in diabetic and HIV associated neuropathy.
Fewer studies addressing oral cannabis.
No good data about CBD oil (topical or oral). Some people say it works for them.
Must take cognitive side effects into account.
• Legal in some states, not in others
Treatment of cramps
No good treatment.
Amazingly, no one really knows why people get muscle cramps.
o Associated with electrolyte abnormalities like salt, calcium and magnesium
• Amazingly, there are not great treatments for muscle cramps
o Staywellhydrated
o Stretch muscles for 10 minutes before bed
o Magnesium supplement (250 mg/day) *Check with your doctor first!
o FDA warning against using quinine
Treatment of Restless Legs
Check iron level and supplement if low
Stretching the legs before bed
Warm or cool packs
Regular exercise
Cut out caffeine for a few weeks
Relaxation techniques before bed
Sleep hygiene
o Regular bedtime
o Cool dark room
o No screens for 2 hour before bed
Medications for Restless Leg Syndrome
Ropinirole (Requip), rotigotine (Neupro) and pramipexole (Mirapex) are approved by the FDA for RLS. These medicines are also used for Parkinson ’s disease.
Gabapentin (Neurontin) and pre-gabalin (Lyrica) may help and have fewer side effects.
Short-acting, Valium-like drugs such as clonazepam (Klonopin) may help but are addictive.
Treatment of motor symptoms
No medication to help with strength
Physical therapy
Assistive devices
Treatment of Autonomic Symptoms
Dry eyes – Artificial tears during the day and lacrilube at night
Dry mouth – Biotene and Xylimelt products
Skin changes – Moisturizer
Low blood pressure
o Decrease or discontinue high blood pressure medications with your doctor’s advice
o Stay as well hydrated as your heart can handle
o Sit-upandstand-upslowly
o Compression stockings–must be thigh high!
o Medications
▪ Midodrine (ProAmatine)
Fludrocortisone (Florinef)
Droxidopa (Northera)
Early satiety
o Small, low fat meals
o Metoclopramide(Reglan)
• Diarrhea
o Lomotil and Imodium are over-the-counter ▪ Talk to your doctor
o Tinctureofopium
• Constipation
o Many OTC laxatives
▪ Osmotic (miralax, prunes, bran cereal)
▪ Stimulant (Dulcolax)
o Linzess by prescription
Erectile dysfunction (men and women)
o Take it slow
o Viagra-like medications
▪ Require some nerve function to work
▪ Other treatments can be discussed with a urologist
Decreased vaginal lubrication
o Take it slow
o Vaginal lotions
o Estrogen supplements
Things advertised on the Internet
Private Neuropathy clinics
Alpha-lipoic acid – Lowers blood sugar
Neuracel and other pills
o FDA is forbidden from regulating supplements
• Other crazy contraptions
A word about foot care!!!
If you can’t feel your feet you can’t feel cuts or sores that can become infected.
▪ Foot care tips
o Look between and under your toes every day o Wear soft, well-fitting shoes
o Donotwalkbarefoot,particularlyoutside
o Keep feet soft and well moisturized
o Have nails filed rather than cut
o A podiatrist or specialized pedicurist can help o Don’t cut your own nails!!
▪ Neuropathy leads to decreased blood flow, and decreased antibiotic delivery, to the feet
▪ We want you have all 10 toes, all of the time!
Lifestyle changes
▪ Exercise is good
o You don’t hurt the nerves with exercise
▪ Sex – yes
▪ Sleep
o A good night’s sleep makes the next day easier
▪ Healthy eatingWhat you can do for healthy nerves
1. CUT DOWN ON ALCOHOL – it is directly toxic to nerves
2. STOP SMOKING – with every puff you cause constriction of the blood
3. EAT A LOT OF FRUITS AND VEGETABLES, especially dark green leafy vegetables which contain b vitamins (but not if you are taking warfarin)
4. Muscles depend on their nerve supply to stay healthy – USE THEM both
▪ Healthy Nerves pamphlet on ASG website
▪ Boston University Amyloid Treatment and Research Website
o Podcast
o Healthy Nerves pamphlet
▪ New book: Peripheral Neuropathy: What It Is and What You Can Do To Feel Better
A word about wtATTR
▪ With age wtATTR deposits in a variety of tissues
o Heart (Heart failure with no EF, 13%. aortic stenosis surgery 16%)
o Ligamentum flavum of the spine (lumbar spine stenosis, 50%)
o Biceps tendon (rupture)
o Flexor retinaculum of the wrist (CTS)

Nervous system and eyes

Central Nervous System and Ocular involvement in hATTR
Chafic Karam, MDAssociate Professor of Neurology, Director of the ALS and Neuromuscular Center and Director of the Neuromuscular Medicine Fellowship program at the OHSU Brain Institute
What organs are involved?
Eye and brain produce TTR, like the liver. They produce it more slowly that the liver, so it takes longer for problems to occur.  The Blood Brain Barrier (BBB) prevents many substances in most of the circulatory system’s blood from reaching the eyes and brain, and vice versa.
Transthyretin TTR
Produced by things other than the liver. The eye and brain produce TTR (or ATTR, and the problematic amyloid deposits).
CNS TTR symptoms:
Episodes of confusion, psychosis
Headache (severe migraine like- SAH)
Transient or focal neurological events (FNE)
vessels that nourish nerves
Cognitive issues, dementia (superficial siderosis )
Ataxia, unsteadiness (superficial siderosis)
Hearing loss (superficial siderosis)
Vision loss
Stroke (cerebral amyloid angiopathy)
Mutations with known risk for CNS TTR complications
Mutations reported: A18G, A36P, A25T, G53A, L12P, P64S, Ser44, L58A, T114C, T49P, T69H, V30G, V30M Rarely can occur without peripheral neuropathy (A18G)
In general late manifestation of the disease >10 years (usually in slow progressive disease)
Or in patients treated with liver transplant – eyes and brain secrete TTR more slowly than liver, so impact is often much later.
CNS compilations after Liver Transplant
87 patients with V30M who underwent liver transplant
31% had Focal neurological events (FNE) (stroke, migraine, seizure) FNEs occurred on average 14.6 years after disease onset
Ocular Involvement
Potential Ocular complications hATTR
▪ Pupillary light-near dissociation (Common)
▪ loss of corneal sensitivity and neurotrophic corneal ulcers (rare)
▪ anterior capsule opacity of the lens (rare)
▪ keratoconjunctivitis sicca (Common)
▪ chronic open-angle glaucoma (rare)→LEADING CAUSE OF BLINDNESS
▪ vitreous opacities (rare)
▪ abnormal conjunctival vessels (common)
▪ optic neuropathy (from ischemia)
▪ retinal vascular changes
Source: BioMed Research International, vol. 2015, Article ID 282405; BMB reports 48(4)
Certain patients more predisposed: Tir114Cis (100%) and Lys 54 mutations than in patients with variant Val30Met (24%)
Rarely can be first presenting sign
477 patients (343 had been liver transplanted)
▪ 80% had dry eyes
▪ 39% had amyloid deposition on the iris
▪ 33% amyloid deposition on the anterior capsule of the lens ▪ 28% scalloped iris
▪ 20% glaucoma
▪ 17% vitreous opacities
Vitreous opacities
▪ Complicates between 5 and 35% of hATTR patients ▪ Can manifest as floaters and visual loss
Hearing Involvement
▪ Potential Hearing Complication in hATTR
▪ Conductive hearing loss due to amyloid infiltration of the middle ear ▪ Sensorineural hearing loss due to cochlear and/or neural infiltration ▪ Can have both
▪  Brain MRI can show Leptomeningeal enhancement, stroke, bleeding or evidence of prior bleeding (hemosiderin deposits)
▪  CT scan in case brain MRI cannot be done
▪  EEG for seizures
▪  Audiometry can demonstrate hearing loss
▪  Eye examination
Local treatment
• Eyes
o Dry eyes: Eye drops, topical cyclosporine
o Vitrectomyiffloatersaresevere
o Glaucoma: topical treatment, surgery (trabeculectomy with mitomycin C)
o Laser for retinal angiopathy
Hearing loss: hearing aids
Blood pressure control to reduce risk of stroke and bleeding
Systemic Treatment
• Unlikely to be helpful
o Livertransplant
o Systemic RNA knock down (unless ASO given in the ventricular system)
o ?Abs
• Possibly helpful (penetrates the Blood Brain Barrier)
o ?Tafamidis
o ?AG10
o ?Diflunisal
o ?Tolcapone o ?Resveratrol o ?Doxycycline o ?TUDCA
CNS complications are rare
Certain TTR mutations have a higher risk of CNS complications
Patients with longer disease, or with liver transplant are at a higher risk of developing CNS complications
Special investigation are necessary to detect whether CNS is involved
Several of the stabilizers may penetrate CSF and affect course of CNS involvement in hATTR amyloidosis

New imaging techniques for diagnosis

Why Image Systemic Amyloidosis?
– Detection of amyloid in the heart, lung, kidney, liver, and spleen (and nerve) using one agent is not currently possible.
– Imaging amyloid can provide more effective and rapid diagnosis.
– The extent of deposition may be of prognostic value and might influence treatment options – and allow physicians to monitor the effect of treatments.
– Currently only one approved method for imaging ATTR in the heart with no agents approved for other forms of amyloidosis.
Imaging ATTR with 99mTc-PyP
• Images showed darkness in heart of ATTR positive pts
Phase 1 Clinical Trial of 124I-p5+14 PET/CT Imaging of Patients with Systemic Amyloidosis
Assessing safety, and some efficacy
Part 1 – Three patients with AL given radioactive p5+14 peptide for initial evaluation of safety.
Patients were imaged 7 times over 48 h – COMPLETED.
Part 2 – Forty patients:
o 20 AL (6 imaged to date)
o 10 ATTR (4 imaged, all hereditary)
o 5ALect2  (1imaged)
o 5Other(1recruited)
Each patient receives a low dose of the peptide and low dose of radioactivity and is imaged at 5 h and 24 h post injection.
Study is assessing safety and determining whether we can image individual organs that are known or suspected of containing amyloid based on the clinical work-up.
Patients receive copies of their images as part of the study.
Imaging protocol
Patients visit our Study Physician for a check up The radioactive drug is prepared at UTMC
The patients come to the Nuclear Medicine Dept
3D PET/CT Imaging allows us to look at many views of the patient (3D imaging).
We continue to study the images from all the patients to understand how the peptide works and what it can “see” but the images suggest that it may be possible to see nerve-associated ATTR.
Scans show where the amyloid deposits are, and where they are not. So it indicates which organs are affected.
Images of patients with only neuropathy symptoms showed obvious deposits in hearts, as well.
ALECT2 amyloidosis
ALECT2 amyloidosis is the third most common form of systemic amyloidosis in the US. Common in people of Mexican descent with most patients in the Southwest US. Amyloid deposits most commonly found in the kidneys, liver, and spleen.
Images showed amyloid in those organs.
AL (light chain)
Images showed amyloid where it was expected in those patients.
Future Plans
The Phase 1 study will continue to recruit for another year (or so) – after which we will extend the study and image as many patients as we can.
Based on feedback from many of the patients that we have imaged we hope to begin the following studies:
  1. Perform repeat imaging on patients at 12 month intervals so that we can monitor response
    to therapy.
  2. Recruit TTR mutant carriers who are asymptomatic to see if very early amyloid detection is
  3. Recruit amyloid-free “heathy” subjects.
  4. Increase the availability for imaging of rare forms of amyloidosis.
Future directions
The Phase 1 study will continue to recruit for another year (or so) – after which we will extend the study and image as many patients as we can.
We continue to work on understanding the peptide and how the images can be used to benefit patients.
The specific reactivity of the peptide for amyloid is being further exploited to develop therapeutics designed to enhance the clearance of tissue amyloid.
The peptide is being developed by a company (Aurora Bio) to make this imaging agent available for widespread use.
CRISPR (gene therapy)
CRISPR-Mediated Therapy for Transthyretin Amyloidosis (ATTR) Mark D. McKee, MD
26 October 2019
Intellia’s approach
Intellia is trying to develop therapies to edit the genes that cause hATTR.
The idea – put gene editing tools into the body. The tool would enter cells, and edit the protein, alter the DNA (insert corrected DNA, or knockout the defective portion).
Intellia is trying the knockout approach
The knockout tool finds the problematic portion of gene & cuts it out. The body repairs it – if it gets repaired as it was, it is found a cut out again. Eventually, it gets repaired “incorrectly” (i.e., with different nucleotides), so it stays there. But it probably won’t form a good protein, so the no protein at all gets produced.
It may just take one dose, since one dose may change all the problematic genes.
Lipid Nanoparticles (LNPs)
Large cargo capacity for CRISPR/Cas9
Transient expression
Scalable synthetic manufacturing
Redosing capability
Low immunogenicity
Adjustable range of tissue tropism
Intellia’ formulation encapsulating these
Editing in vivo requires cargo release, mRNA translation, RNP assembly and Cas9 import into the cell’s nucleus
sgRNA: Modification of sgRNA to Improve Potency
sgRNA chemical modification campaign identified active modification pattern
Increased potency relative to standard end-modified sgRNA
Guide-sequence independent
Intellia’s CRISPR Development, so far
In vitro (in a lab dish): Modified LNPs to make more edits per dose
In live mice: determined what dose achieved a high and durable level of editing
In live transgenic mice (mice bread to carry human DNA): Demonstrated treatment could decrease amount of a non-amyloid substance in various tissue.
In live primates: demonstrated >95% decrease in TTR production after treatment.
TTR LNPs enable >95% knockdown of TTR protein by single-dose editing of TTR across multiple species, including mouse and NHP
Reduction of circulating levels of TTR sustained for at least 12 months in mice and for 10 months in NHP
No significant histopathology findings noted
Rescue of amyloid deposition in multiple tissues seen in humanized mouse model
Modular platform for LNP-delivered CRISPR/Cas9 gene editing may enable future treatments for multiple genetic diseases
Next steps
  • Manufacturing of NTLA-2001 Phase 1 materials
  • Submit for FDA approval in mid-2020
Lifestyle and equipment aids
Rehabilitation Considerations in Amyloidosis: Practical Help and Assistive Devices Sarah Boyd, P.T., D.P.T.
Sarah Dahlhauser, O.T., O.T.D.

Signs and Symptoms

Therapy can help with all of these symptoms:
Cardiac and respiratory issues
Difficulty swallowing
Dizziness or feeling faint upon standing
Fatigue and weakness
Gastrointestinal issues (diarrhea/constipation)
Numbness, tingling, and pain in hands or feet
Skin changes
Swelling of ankles and legs
Unsteadiness when walking
Weight loss
Occupational Therapy vs. Physical Therapy
Help focused on any activity that occupies your time.
Specialists aiming to improve and restore your ability to perform daily activities within the home, hobbies, or job through restorative training or compensatory training using adaptive equipment.
Movement specialists aiming to maintain, improve or restore mobility and prevent disability through specialized interventions addressing strength, flexibility, balance, posture, endurance, and pain.
How can rehabilitation help?
Safety and mobility assessment
Adaptive equipment
Pain management
Swallow evaluation and recommendations
Caregiver and family training
What is YOUR goal?
Safety and Mobility Assessment
• Requires an evaluation by neurologic-based physical and/or occupational therapists
o Periodic re-evaluations are recommended
• If there are safety concerns, the following may occur:
o Consideration of activity compensation/adaptation – e.g., put a chair in the shower o Trialofgaitaids
o Education on falls prevention with home modifications
o Educationonwhattodoifyoufallandhowtogetup
Mobility Aids – Physical Therapy
Mild: Canes, walking stick
Moderate: Walkers of various types, transport chairs
Severe: Wheelchairs of various types
Lower Body Orthotics
Certified orthotist will make the brace for you
Recommended for:
o Lower body weakness – foot drop, knee buckling, “rolling my ankle”
o Joint positioning and protection
o Maximising walking efficiency
o Prevent falls
• Various styles and material
o Off-the-shelf vs. customized
o Plastic vs .carbonfiber
Adaptive Equipment – Occupational Therapy
• Safety Equipment
o Showerchair/tubtransferbench o Grabbars
o Toiletsafetyframe
o Bed rail
o Lift chairs
• Lighting
• Daily Activity Aids
o Buttonhook(tobuttonshirts)
o Sockaid(toputonsocks)
o Reacher
o Rocker knife (much easier to cut foods than with standard knife)
o Built-uphandles(easiertohold)o Rubberfingers(easiertograbthings-bettertraction)
o Dycem(preventslipping)
o Multi-PurposeOpenerEquipment Acquisition Process (paying for it, insurance)
• Durable Medical Equipment (DME)
▪  Wheelchairs will need consultation with physician and wheelchair/seatingspecialist (OT or PT)
▪ Local medical institutions or rehabilitation centers will be able to direct you to local DME resources (vendors)
o If you have bracing needs, pursue a local orthotist for brace fabrication
• Adaptive Equipment
Day-to-day Strategies
• If feeling dizzy or lightheaded upon standing:
o Perform leg movements (i.e. bottom squeeze, ankle pumps)
o Take transitions slowly; pauses
• Simple modifications to implement when eating or drinking:
o Small bites and sips
o Eat slowly
o Chew well
o Chin tuck before swallowing
o Alternate solids and liquids
Discuss with your primary care provider or medical team for an evaluation within with Physical and Occupational Therapy
Get a special request for neurologic-focused rehabilitation
  • • Adaptive Equipment
David Hurwitz, Ph.D., Field Medical Director, Akcea Therapeutics
Update on TEGSEDI® safety and efficacy
Overview of clinical trial study results
  • How TEGSEDI WorksHinders the creation of the ATTR protein by obstructing the RNA the creates the ATTRPivotal Phase II/III Study (safety & efficacy)TEGSEDI® was studied in a clinical trial of 172 patients with nerve damage from hereditary ATTR amyloidosis
    TEGSEDI was associated with significant improvement in nerve damage compared with placebo
• 36% of TEGSEDI pts improved nerve function, vs. 19% of placebo pts. Quality of Life improved vs. placebo, too.
Summary of OLE Study Results
Starting TEGSEDI® earlier leads to better outcomes on measures of neuropathy progression and neuropathy-related quality of life.
Initiation of TEGSEDI in patients previously given placebo resulted in disease improvement versus natural history in neuropathy-related quality of life
TEGSEDI exposure evaluated up to 39 months resulted in continued efficacy.
With exposure up to five years, TEGSEDI was not associated with any additional safety concerns.
With enhanced monitoring, platelet and renal monitoring have been effective in the OLE study No new safety signals were identified in the open-label extension study

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