Neurological Diseases

Neurology-
Encouraging but Unpredictable and Sporadic miraculous results are observed in patients with various neurodegenerative disorders ranging from
Autism
cerebral palsy,
spinal cord injury,
stroke,
parkinsons
motor neuron disease,
optic atrophy

How it works-

1- HOMING
Because of Chemokines secreted by Damaged tissue Neurotrophic Growth factors added along with stem cells
Blood-Brain Barrier :
Avoided using Intrathecal approach
Also made permeable by selective use of drugs

2-THERAPEUTIC ANGIOGENESIS
Because of presence of Endothelial Stem cell Population in Cocktail along with Platelets and Growth factors
Stem cell treatment induces angiogenesis, Predominantly responsible for tissue repair
Intravenous injection of MSCs after induced stroke resulted in augmented levels of endogenous VEGF as well as increased angiogenesis in transition zone

3-REJUVENATION
Secrete growth factors which Modulate the Locoregional Milieu :
• promote self-repair of residing tissue cells.
• reactivate dormant neurons
• Remyelination of Denuded Axons
Glial Cell-Line Derived Neurotrophic Factor (GDNF)
Brain-Derived Neurotrophic Factor (BDNF)
Nerve Growth Factor (NGF)
Vascular Endothelial Growth Factor(VEGF)
Hepatocyte Growth Factor (HGF)

4- REGENERATION
Engraftment and Transdifferentiation
After homing and subsequent survival of MSCs, their differentiation into neurons and astrocytes, leading to enhanced neural function (The concept of plasticity of stem cells or transdifferentiation )

MSCs have also been shown to differentiate into neurons vivoand in vitro

Bone marrow derived MSCs differentiation into neural cells under appropriate stimuli

The Research behind the methodology


Intensive animal research and encouraging results from proof of concept studies support the concept

How it is done-

Patients are evaluated clinically, rdiologicaly by MRI,PETscans ,electrphysiologicaly by EEG,somatosensory evoked potentials
Patients advised to strictly avoid smoking, drug or alcohol consumption and have a positive life style
As a day care procedure 240 ml of Bone marrow and 100 ml of fat is aspirated and processed for stem cells isolation. 2 ml of stem cells processed as per GMP is injected either into
• Intra arterial (BBB)
• Intrathecal (CSF BRAIN BARRIER)
• Direct
underflouroscopic guidance
open-limited Laminectomy
open surgery

Intrathecal application of stem cells

Intralesional administration under fluoroscopic control

Intralesional administration under direct visualistaion limited exposure

Direct implantation during Open surgery

Need of aggresive physiotherapy & Rehabilitation
crucial for these neurons to make functional synapses

What to expect-
AUTISM

 80% (8 of 10) experienced improvements
 Direct correlation between positive outcome and age, number of stem cells administered and frequency.
 Results were significantly better in kids less than 8 year age
 Improved cognition and sensory processing
 Improved attention span
 Improved motor skills and coordination
 More confident
 Reduced hyperactivity
 Improved ability to socialize with others
 Meaningless play has reduced
 Hand and finger motor skill improvement
 Improved handwriting
 Improved speech
 Eating more independently

CEREBRAL PALSY

 Overall,60% improved
 Decrease in arm and hand spasticity 70%
 Improvements in hand and finger motor skills, coordination 60%
 Cognitive improvements materialized after about 3 months and physical improvements started after 6 months.
 Leg and foot coordination improved in 50%
 Reduced lower limb spasticity 50%
 Able to walk 40 %
 Speech improved in almost 60% of patients.
 Improved cognition 20 %
 Attention span and ability to engage others 20%

SPINAL CORD INJURY

 Nearly 65-70%% of the treated patients experienced improvements.
 Patients saw average improvements of about 15% in ASIA motor score, and approximately 20% in ASIA pin prick and light touch measurements over a period of one year.
 Up to 65% of ASIA A patients could recover certain motor functions, increased muscle strength, better stamina during physical exercises, pelvic organs functions and improved bladder control as well as the sensitivity.

VOLUNTARY TRUNK MUSCLE CONTROL

 Sitting without back support and able to stand with support is experienced by 85% of Patients with upper thoracic injury within 4 months.
 Better coordination and walking ability with sensory improvement though motor scores did not improve much was observed in 90% of patients

USEFUL MOTOR AND SENSORY RECOVERY

 Getting back sensation (feeling warm or cold sensations/ touch) was reported in 67%overall enhanced strength 65%
 Improved muscle function and strength, including some ambulation seen in 60% Patientstill about 2 years.
 Bowel-and-bladder function improved in 55 % of patients
 Sexual function- getting back erections was reported by more than 30% of the patients
 Spasticity reduction Spasms induced by attempted movements diminishes significantly in 80% of patients
 Electrophysiological measurements suggested improved nerve conduction through the injury site in 62% of patients
 MRI (magnetic resonance imaging)evaluations indicated increased spinal-cord diameter in 40%

For more information kindly visit: go to pages on spinal cord injury

PARKINSONS

 Total reversal of symptoms in the one patient.
 60 % of patients showed up to 50 %improvement in motor function

STROKE

 Overall 75% patients experienced improvements.
 MRI showed 25 % improvement in thickness of cortex in 60 % of patients
 Better arm use and coordination and improved motor skills in their hands and fingers in 60 %
 Improved leg use and coordination as well as an increased ability to stand and walk unassisted in 70 % of patients
 Speech improved in more than 65% of patients
 Vision improved in 40 %

OPTIC ATROPHY

 Results vary between 40 -60 % depending on cause, duration of the disease, age of the patient.
 In sub acute phase success rate exceeds up to 75 %.
 Improvement in the visual acuity in (58 %) of eyes. It was marked, good and moderate in 20%, 22 %and 16% eyes, respective¬ly. Slight improvement was seen in 2 % of cases.
 No eye showed fur¬ther deterioration of vision
 (52%) showed improved vascularity of the disc, increased calibre of the re¬tinal arterioles and general improvement in the color of the peripheral fundus
 47% was increase in the field of vision, both central and peripheral.
 20% of them had no residual general¬ized peripheral field constriction

Multiple sclerosis -60 -80 million cells injected intrathecally and 60-80 million intravenously given 3 to 5 times.
*Treatment decreased tissue damage in the patients, and had the capacity to
completely suppress further tissue damage
*Clinical efficacy in disability score (MS functional rating scale (EDSS) scale. upto 65 % of patients showed MS functional rating scale (EDSS) scale by at least 2 degree.
*Total volume of lesions in the brain or spinal cord showed reduction up to 25 % in 40 % of patients (MRI)
* Cells tracked them with a paramagnetic material and visualize on MRI confirmed their presence in affected motor areas of the CNS gray matter, hence correlated indication clinical efficacy.
*Clinical effect remained sustained – no major relapse seen in 40 % till now (follow up period of 5 yrs)
Amyotrophic Lateral Sclerosis / Motor Neuron Disease
• The clinical progression of the disease as assessed using the ALSFRS
And the Medical Research Council (MRC) scale showed improvement in 55 % of patients

• Manual muscle testing of 34 muscle groups of the upper and lower limbs showed improvement by at least one grade in 60 % of patients

• Electromyographic assessment of key muscle group of the upper and lower limb showed improvement in 50 % of patients

• Somatosensory evoked potentials (SEPs) following tibial nerve stimulation showed improvement in 55 % of patients

• MRIs – the spinal cord diameter at the level of engraftment showed significant increase. Diameters of the spinal cord of 80 %cases were increased by up to one and a half-fold above the baseline.

• .The median ALS-FRS score at entry was 33 (range: 26–39) while the median FVC was 99% (range:51–117)

• 30 % patients needed PEG percutaneous endoscopic gastrostomy placement by 4yr

• Nocturnal Non Invasive Ventilation was needed for sleep apnea syndrome in 35 % of subjects.
• 20 % patients required tracheotomy 3yrs after transplantation