Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis treatment

with autologous stem cells from your

own bone marrow.

Information for patients

Cells health 4

Health People

ALS

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Amyotrophic Lateral Sclerosis (ALS), also called Lou Gehrig's disease or Motor Neuron Disease, is a rapidly progressive, invariably fatal neurological disease that attacks the nerve cells (neurons) responsible controlling the voluntary muscles. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die,ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, waste away (become atrophic), and typically twitch (fasciculate).

Eventually the incapability of the brain, to start and controlvoluntary movement is the triggering mechanism.Individuals with ALS lose their strength and the ability to move their arms, legs, and body. When muscles in the diaphragm and chest wall fail, individuals finally lose the ability to breathe without ventilatory support. The disease

does not affect a person's ability to see, smell, taste, hear, or recognize touch, and it does not usually impair a person's thinking or other cognitive abilities.

However, several recent studies suggest that a small percentage of patients may experience problems with

memory or decision-making, and there are subtypes that may even lead to a form of dementia. The cause of ALS is not known, and scientists do not yet know, why ALS strikes some people and not others.

Is there any treatment?

No cure has yet been found for ALS. However, the USFDA has approved the first drug treatment for the diseaseriluzole. Riluzole is believed to reduce damage to motor neurons and prolongs survival by several months, mainly in those patients with swallow-ing difficulty. Other treatments are designed to relieve symptoms and improve the quality of life for people with ALS. Drugs are available to help individuals with pain, depression, sleep disturbances, and constipa-tion. Individuals with ALS may eventually consider forms of mechanical ventilation (respirators) and implantation of gastric feeding tubes.

Besides these kinds of treatments, stem cell therapy can be used to improve some symptoms and to slow down the chronic consequences of ALS.

What is the prognosis?

Regardless of the part of the body first affected by thedisease, muscle weakness and atrophy spread to other parts of the body as the disease progresses. Individuals have increasing problems with moving, swallowing, and speaking. This means people with ALS will not be able to stand or walk, to get in or out of bed on their own, and to use their arms and hands. They loose the ability to communicate by understand-able words and cannot swallow fluids, later also not solid food.

In advanced stages of the disease, individuals have difficulty breathing as the auxiliary respiratory muscles weaken. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS.

Most people with ALS die from respiratory failure, usually within 3 to 5 years from the onset of the first symptoms, however, about 10 percent survive for 10 or more years.

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About Stem Cells

The discovery of the stem cell has lead to a revolution in modern medicine. Stem cells are in fact, the “smart cells” of our bodies. These cells migrate to injured areas within the body and transform themselves into new tissue cells that replace the damaged ones. The body repairs itself by continuously producing new cells and tissues in this manner. Stem cells have the capacity to multiply and to renew themselves almost indefinitely. This contrasts with nerve cells, muscle cells and blood cells, which cannot multiply themselves and have limited life spans. Stem cells can also develop into specialized cells.

The Cells4health ALS Treatment

The entire procedure consists of the following phases:eligibility, stem cell collection and processing, stem celltreatment, and follow-up.

Objectives

The objective of the treatment is to recover as much aspossible of the lost functions caused by Amyotrophic lateral sclerosis (ALS).

Type of treatment

The procedure employs autologous adult stem cells. These cells are collected from your own bone marrow.A few days prior to treatment, the stem cells will be isolated from bone marrow taken from your hip (iliac crest).

Stem cells from the bone marrow can develop into cardiac muscle, as well as liver, brain, nerve, fat and skin tissue.

Examples of bone marrow-derived stem cell develop-ment are illustrated below

Liver

Brain

Blood cell

Cardiac muscle

Adult Stem Cell

Skeletal muscle

Bone marrow

Epithelial cell

Neuron

Stem Cell

Specialized Cell(e.g., neuron)

Stem Celle.g., hematopoietic stem cell

Amyotrophic Lateral SclerosisCells health 4

Preparation Application of local anesthetic

Disinfection of the collection site Needle insertion into the hip bone Sample collection

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Eligibility phase

If you meet the following conditions, you are eligible for treatment:

- ALS diagnosis based on your medical history, imag- ing material such as MRI or CT scan, neurophysiol- ogy, and medical and neurological reports.

- The Cells4health medical team approves you for treatment.

- Your bone marrow contains a sufficient quantity of viable stem cells. This is assessed during the processing phase.

(iliac crest)

Bone Marrow

Collection

Procedure

These pictures show the Bone Marrow Collection Procedure

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Stem Cell Collection and Processing

Prior to scheduling bone marrow collection, you will be asked to fill out the patient consent form. This form grants explicit written permission for bone marrow collection. You must discontinue using any blood diluting medications at least 10 days before your collection date. You should consult your physician before discontinuing the use of blood diluting drugs.

When we greet you on the collection day, we’ll have everything prepared to begin collection and make it comfortable for you. Our physician will collect approxi-mately 150 – 200 ml of bone marrow from your hip bone. Stem cell collection is performed as an out-patient procedure under local anesthesia in sterile conditions. It is comparable in pain to a dentist visit.

During the collection, you will barely feel the needle insertion into your hip bone.Afterwards, the collection site might look like a “blue spot” and be a bit painful for 3 – 4 days.

Normally, there are no other side-effects. Theoreti-cally, there is a small risk of infection. We minimize this risk by working in a sterile environment.

Within 24 hours, the stem cell samples are processed and quality tested by a highly specialized laboratory in totally sterile, clean room conditions. Since they are kept in sterile tubes and never come into contact with the air, these samples cannot be contaminated.

Bone marrow processing and quality testing consists of:

- Stem cell isolation – stem cells are separated from the red blood cells and blood plasma.

- Stem cell counting

- Stem cell vitality measurement

- Stem cell processing results are documented in an analysis report.

The result is positive if:

- There are more than two million (2,000,000) CD34+ stem cells present.

- The CD34+ stem cells have a vitality greater than 80%

- Positive isolated stem cell samples are stored in sterile tubes at -196°C in liquid nitrogen.

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Stem Cell Implantation

Your high-quality stem cell sample will be implanted into the spinal canal via intrathecal injection.

Intrathecal InjectionUnder a local anesthesia, your stem cells (in a volume of 4 - 10 ml) will be injected directly into the cerebros-pinal fluid via a lumbar puncture.

By the natural cerebrospinal fluid circulation, the stemcells are distributed and transported directly to the damaged tissue in the brain or the spinal cord. The entire procedure usually takes about 30 - 60 minutes, depending on the volume.Immediately after treatment, you will spend about three to four hours laying in bed in our recovery room for observation. As with any minimally invasive intervention, intrathecal stem cell implantation carries a very small risk of infection. We minimize this risk by working in a sterile environment and by prescribing prophylactic antibiotics to you. If there are no compli-cations, you can then return home or to your hotel.

General

No additional charges will be incurred unless you are required to extent your stay at the medical center as a result of complications. Costs do not include additional stem cell treatments. If another treatment is neces-sary, we will discuss potential options with you.

You will receive an invoice one week prior to treatment. This invoice must be paid in-full before treatment can begin.

Note: If your bone marrow sample is negative or the stem cells cannot be administered due to unforeseenmedical circumstances, you will only be required to pay charges incurred to that point. In the case of a negative bone marrow sample, it might be possible to schedule another bone marrow collection.

Possible Adverse Events from the treatment

After the procedure, you might experience the follow-ing adverse events. These events can be intense, but usually subside within two or three days.

- Nausea- Headache- Backache and/or leg pain

Advantages of application via lumbar puncture:

- Easy performance- Outpatient treatment- Less invasive than surgery- Lower cost than surgery

Follow-up

Once you have returned home, a member of our medi-cal team will monitor your progress in given intervals via telephone and email. For your convenience, a telephone 'hotline' is always at your disposal.

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Amyotrophic Lateral SclerosisCells health 4

ALS PatientsNormal diseaseprogression

Improvement

16

16

ALS - Results of Stem cell Treatment (N=32)

0%

50%

100%

+

ALS Stem Cell Treatment Results

A total number of 32 patients with ALS were treated and followed.

Improvements were reported in 50% of the patients. Most patients reported improvements in muscle strength (56.3%), sensory function (37.5%) and motor function (30.4%). Also more than 25% of the patients reported better fine motor skills. Furthermore, patients reported improvements in speech (25%), eating (25%), bladder/bowel control (12.5%), mental state (18.8%), breathing (12.5%), and weight control (25%).

Type of improvements ALS(n=16/N=32)

0%

50%

60%

70%

80%

90%

10%

30,4 % 18,8 % 25,0 % 25,0 % 12,5 %

20%

30%

40%

100%

No

Yes

Motor Functi

on

Behavior a

nd Intelle

ct

Speech

Eating

Less in

contin

ence

Type of improvements ALS(n=16/N=32)

0%

50%

60%

70%

80%

90%

10%

25,0 % 56,3 % 37,5 % 12,5 % 25,0 %

20%

30%

40%

100%

No

Yes

Fine motoric

Strength

Sensory

functi

on

Breath

ing

Weight contro

l