XCell-CenterInstitute for Regenerative Medicine

Information for patientsNeurological Disorders treatment with autologous adult stem cells from your own bone marrow

What is the prognosis?

PD is both chronic, meaning it persists over a long peri-od of time, and progressive, meaning its symptoms growworse over time. Although some people become severe-ly disabled, others experience only minor motor disrup-tions. Tremor is the major symptom for some patients,while for others tremor is only a minor complaint andother symptoms are more troublesome. No one can pre-dict which symptoms will affect an individual patient, andthe intensity of the symptoms also varies from person toperson.

Cerebral Palsy

The term cerebral palsy refers to any one of a number ofneurological disorders that appear in infancy or earlychildhood and permanently affect body movement andmuscle coordination but don't worsen over time. Eventhough cerebral palsy affects muscle movement, it isn'tcaused by problems in the muscles or nerves. It iscaused by abnormalities in parts of the brain that controlmuscle movements. The majority of children with cere-bral palsy are born with it, although it may not be detec-ted until months or years later. The early signs of cerebral

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Parkinson's Disease

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Parkinson's disease (PD) belongs to a group of conditionscalled motor system disorders, which are the result ofthe loss of dopamine-producing brain cells. The four pri-mary symptoms of PD are tremor, or trembling in hands,arms, legs, jaw, and face; rigidity, or stiffness of thelimbs and trunk; bradykinesia, or slowness of movement;and postural instability, or impaired balance and coordi-nation. As these symptoms become more pronounced,patients may have difficulty walking, talking, or complet-ing other simple tasks. PD usually affects people over theage of 50. Early symptoms of PD are subtle and occurgradually. In some people the disease progresses morequickly than in others. As the disease progresses, theshaking, or tremor, which affects the majority of PDpatients may begin to interfere with daily activities.Other symptoms may include depression and other emo-tional changes; difficulty in swallowing, chewing, andspeaking; urinary problems or constipation; skin prob-lems; and sleep disruptions. There are currently noblood or laboratory tests that have been proven to helpin diagnosing sporadic PD. Therefore the diagnosis isbased on medical history and a neurological examina-tion. The disease can be difficult to diagnose accurate-ly. Doctors may sometimes request brain scans or lab-oratory tests in order to rule out other diseases.

Is there any treatment?

At present, there is no cure for PD, but a variety of med-ications provide dramatic relief from the symptoms.Usually, patients are given levodopa combined with car-bidopa. Carbidopa delays the conversion of levodopainto dopamine until it reaches the brain. Nerve cells canuse levodopa to make dopamine and replenish thebrain's dwindling supply. Although levodopa helps atleast three-quarters of parkinsonian cases, not all symp-toms respond equally to the drug. Bradykinesia andrigidity respond best, while tremor may be only margin-ally reduced. Problems with balance and other symptomsmay not be alleviated at all. Anticholinergics may helpcontrol tremor and rigidity. Other drugs, such asbromocriptine, pramipexole, and ropinirole, mimic therole of dopamine in the brain, causing the neurons toreact as they would to dopamine. An antiviral drug,amantadine, also appears to reduce symptoms. In May2006, the FDA approved rasagiline to be used along withlevodopa for patients with advanced PD or as a single-drug treatment for early PD. Besides these kinds of treatments, stem cell therapy canbe used to minimize the chronic consequences ofParkinson's disease.

with the world.

Other neurological diseases

Other neurological diseases such us Huntington'sDisease, movement disorders, ataxia, neurological intoxi-cations, Alzheimer can be treated with the therapiesdescribed in this document.

About stem cells

The discovery of the stem cell has lead to a revolution inmodern medicine. Stem cells are in fact, the "smart cells"of our bodies. These cells migrate to injured areas with-in the body and transform themselves into new tissuecells that replace the damaged ones. The body repairsitself by continuously producing new cells and tissues inthis manner. Stem cells have the capacity to multiply andto renew themselves almost indefinitely. This contrastswith nerve cells, muscle cells and blood cells, which can-not multiply themselves and have limited life spans.

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accomplish the tasks that challenge them. Treatmentmay include physical and occupational therapy, speechtherapy, drugs to control seizures, relax muscle spasms,and alleviate pain; surgery to correct anatomical abnor-malities or release tight muscles; braces and otherorthotic devices; wheelchairs and rolling walkers; andcommunication aids such as computers with attachedvoice synthesizers. Besides these kinds of treatments, stem cell therapy canbe used to minimize the chronic consequences ofCerebral Palsy.

What is the prognosis?

Cerebral palsy doesn't always cause profound disabilities.While one child with severe cerebral palsy might be unableto walk and need extensive, lifelong care, another withmild cerebral palsy might be only slightly awkward andrequire no special assistance. Supportive treatments,medications, and surgery can help many indivi-dualsimprove their motor skills and ability to communicate

palsy usually appear before a child reaches 3 years ofage. The most common are a lack of muscle coordina-tion when performing voluntary movements (ataxia);stiff or tight muscles and exaggerated reflexes (spastic-ity); walking with one foot or leg dragging; walking onthe toes, a crouched gait, or a "scissored" gait; and mus-cle tone that is either too stiff or too floppy. A smallnumber of children have cerebral palsy as the result ofbrain damage in the first few months or years of life,brain infections such as bacterial meningitis or viralencephalitis, or head injury from a motor vehicle acci-dent, a fall, or child abuse.

Is there any treatment?

Cerebral palsy can't be cured, but treatment will oftenimprove a child's capabilities. Many children go on toenjoy near-normal adult lives if their disabilities areproperly managed. In general, the earlier treatmentbegins the better chance children have of overcomingdevelopmental disabilities or learning new ways to

Stem cells can also develop into specialized cells. Stemcells from the bone marrow can develop into cardiacmuscle, as well as liver, brain, nerve, fat and skin tissue.Examples of bone marrow-derived stem cell develop-ment are illustrated below.

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Objectives

The goal of this treatment is to repair damaged tissue orto reactivate existing cells, thus recovering as much aspossible, functions lost as a result of the particular neu-rological disorder.

Type of treatment

The XCell-ND procedure employs autologous adult

stem cells. These cells are collected from your own bonemarrow. A few days prior to treatment, the stem cells willbe isolated from bone marrow taken from your hip (iliaccrest).

Eligibility phase

If you meet the following conditions, you are eligible fortreatment:

Stem Cell

Specialized Cell(e.g., neuron)

Stem Celle.g., hematopoietic stem cell

Liver

Brain

Blood cell

Cardiac muscle

Adult Stemcell

Skletal muscle

Bone marrow

Epithelial cell

Neuron

The XCell-Center Neurological Disorder Treatment

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

Neurological Disorder (as described above) diagno-sis based on your medical history, imaging materialsuch as MRT or CT scan, radiology and a neurolo-gical report.

The XCell-Center medical team approves you fortreatment.

Your bone marrow contains a sufficient quantity ofviable stem cells. This is assessed during the pro-cessing phase.

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Stem Cell Collection and Processing

Prior to scheduling bone marrow collection, you will beasked to fill out the patient consent form. This form grantsexplicit written permission for bone marrow collection.

You must discontinue using any blood diluting medica-tions at least 10 days before your collection date. Youshould consult your physician before discontinuing theuse of blood diluting drugs.

When we greet you on collection day, we'll have everythingprepared to begin collection and make it comfortable foryou. Your physician will collect approximately 150 - 200 mlof bone marrow from your hip bone. Stem cell collection isperformed as an out-patient procedure under local anes-thesia in sterile conditions. It is comparable in pain to adentist visit. During the collection, you will barely feel theneedle insertion into your hip bone. Afterwards, the collec-tion site might look likea "blue spot" and be a bit painful for3 - 4 days. Normally, there are no other side-effects.Theoretically, there is a small risk of infection. We minimize

Arrival at XCell-Center Preparation Application of local anesthetic

Disinfection of the collection site Needle insertion into the hip bone (iliac crest)

Sample collection

These pictures show the Bone Marrow Collection Procedure

After the procedure, you might experience the followingadverse events. These events can be intense but usuallysubside within two or three days.

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Stem cell isolation - stem cells are separated fromthe red blood cells and blood plasma.Stem cell countingStem cell vitality measurement

Stem Cell Implantation

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

Intrathecal Injection

Under a local anesthetic, your stem cells (in a volumeof4ml-10 ml.) will be injected directly into the cer-brospinal fluid via lumbar puncture. Since the cere-brospinal fluid circulates, stem cells are transporteddirectly to the damaged tissue in the brain or thespinal cord. The entire procedure usually takes about30 minutes. Immediately after treatment, you willspend about three or four hours laying in bed in ourrecovery room for observation. As with any minimallyinvasive intervention, intrathecal stem cell implanta-tion carries a very small risk of infection. We minimizethis risk by working in a sterile environment and byprescribing prophylactic antibiotics to you. If there areno complications, you can return home or to yourhotel.

Possible Adverse Events from the treatment

this risk by working in a sterile environment. Within 48hours, the stem cell samples are processed and qualitytested by a highly specialized laboratory in totally sterile,clean room conditions. Since they are in sterile tubes andnever come into contact with the air, these samples can-not be contaminated.

Bone marrow processing and quality testing consists of:

NauseaHeadacheBackache and/or Leg pain

SimpleOut patient

Treatment advantages:

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stem cell treatments. If another treatment is necessary,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 canbegin.

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

Follow-up

Once you have returned home, a member of our medicalteam will regularly monitor your progress via telephoneand email. For your convenience, a telephone 'hotline' isalways at your disposal.

Cost

The price for the intrathecal treatment is 7.995,- Euros.This price includes:

Bone marrow collection and transportationStem cell processing, storage and transportationStem cell administration XCell-Center medical feesXCell-Center administrative fees

This price does not include travel expenses such asairfares, meals and hotel accommodations.

GeneralNo additional charges will be incurred unless you arerequired to extend your stay at the medical center as aresult of complications. Costs do not include additional

Contact:

XCell-Centerthe Institute for Regenerative Medicinec/o Eduardus-KrankenhausCustodisstraße 3-17D-50679 CologneGermany

Phone: +49221 8025095Fax: +49221 29212550

E-mail: info@xcell-center.comInternet: www.xcell-center.com